1 00:00:05,280 --> 00:00:14,320 >> WELCOME TO INSPIRED SYMPOSIUM 2 00:00:14,320 --> 00:00:18,800 BIT OF A BRAINSTORMING AND BRAIN 3 00:00:18,800 --> 00:00:21,920 CHILD OF MANY OF US WHO WANT TO 4 00:00:21,920 --> 00:00:24,160 BRING THE COMMUNITY TOGETHER. 5 00:00:24,160 --> 00:00:25,600 THANK YOU. THIS WILL BE 6 00:00:25,600 --> 00:00:27,920 RECORDED AND ARCHIVED FOR THOSE 7 00:00:27,920 --> 00:00:32,720 THAT ARE UNABLE TO SEE IT LATER. 8 00:00:32,720 --> 00:00:35,720 RECENT ADVANCES IN FUTURE 9 00:00:35,720 --> 00:00:37,400 DIRECTIONS, WELCOME. THE GOALS 10 00:00:37,400 --> 00:00:41,120 ARE TO HIGHLIGHT LESSONS LEARNED 11 00:00:41,120 --> 00:00:44,560 FROM EXPERIENCE OF CAR T-CELLS 12 00:00:44,560 --> 00:01:01,920 FOR CHILDREN AND YOUNG ADULTS. 13 00:01:01,920 --> 00:01:03,320 >> ADAM LAMBLE AND KEVIN 14 00:01:03,320 --> 00:01:09,840 MCNERNEY. 15 00:01:09,840 --> 00:01:11,880 THE FIRST SESSION IS 16 00:01:11,880 --> 00:01:14,200 CURRENTS BEST PRACTICES USING 17 00:01:14,200 --> 00:01:17,960 CAR T-CELLS FOLLOWED BY RELAPSE 18 00:01:17,960 --> 00:01:21,520 PREVENTION AND SESSION 3 IS CAR 19 00:01:21,520 --> 00:01:22,840 T-CELL EMERGENT TOXICITY 20 00:01:22,840 --> 00:01:24,520 PREVENTION AND MANAGEMENT AND 21 00:01:24,520 --> 00:01:26,120 WILL HAVE TWO CONCURRENT 22 00:01:26,120 --> 00:01:28,720 SESSIONS DURING SESSION 4 THAT 23 00:01:28,720 --> 00:01:32,640 IS 4A SPECIAL CAR T-CELLS IN 24 00:01:32,640 --> 00:01:37,280 UNIQUE POPULATIONS AND 4A IS IN 25 00:01:37,280 --> 00:01:39,280 MAIN AUDITORIUM AND 4B WILL BE 26 00:01:39,280 --> 00:01:42,440 NEXT 1 AND E2 AND SESSION 5 27 00:01:42,440 --> 00:01:46,560 EXPANDING USE OF CAR T-CELLS AND 28 00:01:46,560 --> 00:01:47,600 B CELLS. 29 00:01:47,600 --> 00:01:50,080 AND WE WILL START THE 30 00:01:50,080 --> 00:01:52,440 INTRODUCTION AND MORNING KEYNOTE 31 00:01:52,440 --> 00:01:55,880 FOLLOWED BY OUR PATIENTS 32 00:01:55,880 --> 00:01:57,560 EXPECTED PRESENTED BY PATRICK 33 00:01:57,560 --> 00:01:59,480 MCSWEENEY AND GO TO SESSIONS 1 34 00:01:59,480 --> 00:02:01,640 AND SMALL BREAK BEFORE GOING 35 00:02:01,640 --> 00:02:04,920 INTO SESSION 2. BETWEEN SESSION 36 00:02:04,920 --> 00:02:08,600 2 AND LUNCH WE WILL HAVE A 37 00:02:08,600 --> 00:02:10,000 PROFESSIONAL PHOTOGRAPHER HERE. 38 00:02:10,000 --> 00:02:11,640 I WOULD LIKE TO ASK EVERYONE TO 39 00:02:11,640 --> 00:02:14,480 COME UP TO THE STAGE AND KEEP A 40 00:02:14,480 --> 00:02:16,240 REMINDER FOR THAT AND CUTTING TO 41 00:02:16,240 --> 00:02:19,120 E1 AND E2 THAT IS ON YOUR AGENDA 42 00:02:19,120 --> 00:02:21,520 FOR THE LUNCH SYMPOSIUM AND 43 00:02:21,520 --> 00:02:23,200 LUNCH KEYNOTE AND SESSIONS 3 44 00:02:23,200 --> 00:02:25,200 WILL BE BACK IN HERE AND AGAIN 45 00:02:25,200 --> 00:02:26,840 SESSION 4 IS THE CONCURRENT 46 00:02:26,840 --> 00:02:29,600 SESSION WITH 4A IN MAIN 47 00:02:29,600 --> 00:02:32,080 AUDITORIUM AND 4B AND E1 AND E2 48 00:02:32,080 --> 00:02:34,480 AND END THE DAY WITH SESSION 5 49 00:02:34,480 --> 00:02:38,520 AND FINAL KEYNOTE FROM KRYSTAL 50 00:02:38,520 --> 00:02:41,200 MAIPLE AND STEPHEN GOD CHECK AND 51 00:02:41,200 --> 00:02:43,560 WE WILL END THE DAY. 52 00:02:43,560 --> 00:02:45,720 THIS IS A COMBINATION OF ALL 53 00:02:45,720 --> 00:02:47,600 SPEAKERS AND YOU CAN TELL IT IS 54 00:02:47,600 --> 00:02:50,520 A REALLY IMPRESSIVE GROUP. A 55 00:02:50,520 --> 00:02:52,240 COUPLE HOUSEKEEPING THINGS, NO 56 00:02:52,240 --> 00:02:55,840 FOOD IS ALLOWED IN THE MAIN 57 00:02:55,840 --> 00:02:57,520 AUDITORIUM AND LUNCH SYMPOSIUM 58 00:02:57,520 --> 00:03:00,960 IN 4B IS NEXT 1 AND E2 AND IT 59 00:03:00,960 --> 00:03:05,120 WILL BE RECORDED AND NIH 60 00:03:05,120 --> 00:03:07,560 VIDEOCAST AND EVERYONE SHOULD 61 00:03:07,560 --> 00:03:09,000 HAVE GOTTEN THE LINK. THIS 62 00:03:09,000 --> 00:03:11,840 MORNING WE HAD A LITTLE OVER 450 63 00:03:11,840 --> 00:03:15,200 PEOPLE REGISTER AND 100 ARE 64 00:03:15,200 --> 00:03:17,960 ONSITE AND EXCEPTION IS 4B IS ON 65 00:03:17,960 --> 00:03:19,640 WEBEX. I WILL GO THROUGH 66 00:03:19,640 --> 00:03:21,240 LOGISTICS WHEN WE GET THERE. 67 00:03:21,240 --> 00:03:23,240 STAYING ON TIME AND TO END TODAY 68 00:03:23,240 --> 00:03:25,240 IS REALLY ONLY THE BEGINNING. 69 00:03:25,240 --> 00:03:27,160 THESE ARE RAPID FIRE SESSIONS 70 00:03:27,160 --> 00:03:29,240 AND NOBODY IS GIVEN MORE THAN 10 71 00:03:29,240 --> 00:03:31,560 MINUTES. IT IS SCRATCH OF THE 72 00:03:31,560 --> 00:03:33,720 SURFACE OF ALL WE LEARNED IN THE 73 00:03:33,720 --> 00:03:35,120 PAST DECADE. CONFERENCE IS 74 00:03:35,120 --> 00:03:38,080 FOLLOWED BY A SERIES OF SIX 75 00:03:38,080 --> 00:03:39,120 MANUSCRIPTS THAT WILL HELP TO 76 00:03:39,120 --> 00:03:41,360 PROPEL THE FIELD AND ONGOING 77 00:03:41,360 --> 00:03:42,240 CONVERSATIONS THAT WILL HAPPEN 78 00:03:42,240 --> 00:03:43,360 AFTER THE CONFERENCE AND 79 00:03:43,360 --> 00:03:45,400 THINKING ABOUT INSPIRED 2 AND 80 00:03:45,400 --> 00:03:47,600 THAT IS IN 2 TO 3 YEARS HOPING 81 00:03:47,600 --> 00:03:50,080 WE CAN BE ACROSS THE ATLANTIC 82 00:03:50,080 --> 00:03:52,480 FOR THAT ONE AND FINAL THANK YOU 83 00:03:52,480 --> 00:03:55,560 TO PATIENT INHERENT SPEAKERS AND 84 00:03:55,560 --> 00:03:58,240 RESEARCH PROGRAM PROVIDING 85 00:03:58,240 --> 00:04:01,880 FUNDING FOR PCTC WHO PROVIDED 86 00:04:01,880 --> 00:04:03,640 FOOD FOR CONFERENCE AND 87 00:04:03,640 --> 00:04:04,520 [INDISCERNIBLE] WHO I HAVE KNOWN 88 00:04:04,520 --> 00:04:06,880 SINCE I WAS A FELLOW AND WITH 89 00:04:06,880 --> 00:04:09,720 EVERYTHING I DO TO MY LEUKEMIA 90 00:04:09,720 --> 00:04:12,200 TEAM ALL OF THE LITTLE MINIONS 91 00:04:12,200 --> 00:04:12,840 THAT HELPED WITH EVERY 92 00:04:12,840 --> 00:04:14,160 ORGANIZATION THING THAT HAPPENED 93 00:04:14,160 --> 00:04:17,560 TODAY AND AV AND IT PEOPLE I 94 00:04:17,560 --> 00:04:19,120 E-MAILED MILLIONS OF YOU OVER 95 00:04:19,120 --> 00:04:20,520 THE LAST COUPLE DAYS. 96 00:04:20,520 --> 00:04:21,840 YOU MADE THIS ALL POSSIBLE. 97 00:04:21,840 --> 00:04:23,520 THANK YOU. WITH THAT, I WOULD 98 00:04:23,520 --> 00:04:28,640 LIKE TO GO AHEAD AND INTRODUCE 99 00:04:28,640 --> 00:04:30,880 STEPHEN GRUPP WHO IS A SECTION 100 00:04:30,880 --> 00:04:33,600 CHIEF FOR CELL THERAPY AND 101 00:04:33,600 --> 00:04:37,320 TRANSPLANT SECTION AND INAUGURAL 102 00:04:37,320 --> 00:04:47,600 DIRECT YOOR OF SUSAN S STEVEN P 103 00:04:47,600 --> 00:04:53,280 KELLY THEATRE AND HE HOLDS A 104 00:04:53,280 --> 00:04:55,080 [INDISCERNIBLE] CHAIR IN 105 00:04:55,080 --> 00:04:56,200 PEDIATRIC ONCOLOGY AND EVERYONE 106 00:04:56,200 --> 00:04:59,280 KNOWS HIM WELL AND HE IS 107 00:04:59,280 --> 00:05:00,760 ATTENDING PHYSICIAN CANCER 108 00:05:00,760 --> 00:05:11,240 CENTER CHIEF OF THERAPY AND 109 00:05:35,840 --> 00:05:36,240 TRANSPLANT SECTION AND. 110 00:05:36,240 --> 00:05:38,640 >> WITH THAT, I WOULD LIKE TO 111 00:05:38,640 --> 00:05:41,440 HAND IT TO STEVE GRUPP. 112 00:05:41,440 --> 00:05:44,240 >> ALL RIGHT. WELL, THANK YOU 113 00:05:44,240 --> 00:05:47,600 VERY MUCH. I AM HIGHLY AWARE OF 114 00:05:47,600 --> 00:05:51,040 THE NEED TO KEEP WITHIN TIME AND 115 00:05:51,040 --> 00:05:53,920 WOULD ENJOY THE PROSPECT BEING 116 00:05:53,920 --> 00:05:57,560 PUSHED OFF THE STAGE WITH NIRALI 117 00:05:57,560 --> 00:06:00,760 THAT I'M PERFECTLY CAPABLE OF 118 00:06:00,760 --> 00:06:02,760 DOING AND EXCITED TO TALK TO THE 119 00:06:02,760 --> 00:06:04,640 GROUP IN THIS IMPORTANT DAY AND 120 00:06:04,640 --> 00:06:07,760 TITLE TODAY REFLECTIONS OF 121 00:06:07,760 --> 00:06:09,360 EMERGENT CHALLENGE IS A PERFECT 122 00:06:09,360 --> 00:06:12,120 TITLE AND ALL CHALLENGES WERE 123 00:06:12,120 --> 00:06:13,120 EMERGENT AND NOTHING WE THOUGHT 124 00:06:13,120 --> 00:06:15,280 WE KNEW GOING INTO THE BUSINESS 125 00:06:15,280 --> 00:06:17,080 WAS THINGS THAT TURNED OUT TO BE 126 00:06:17,080 --> 00:06:22,120 ACTUALLY TRUE. WE WILL TALK 127 00:06:22,120 --> 00:06:24,520 ABOUT WHERE I THINK THINGS ARE 128 00:06:24,520 --> 00:06:26,960 AND ISSUES THAT WE HAVE RUN INTO 129 00:06:26,960 --> 00:06:29,680 ALONG THE WAY AND MY DISCLOSURES 130 00:06:29,680 --> 00:06:32,800 AND RED ONES IN RED ARE SLIGHTLY 131 00:06:32,800 --> 00:06:34,600 TANGENTIAL TO STUFF WE WILL TALK 132 00:06:34,600 --> 00:06:45,040 ABOUT IN THE NEXT 15 MINUTES. 133 00:06:45,040 --> 00:06:50,080 WE ARE TALKING ABOUT A 10 YEAR 134 00:06:50,080 --> 00:06:55,080 JOURNEY AND. 135 00:06:55,080 --> 00:06:57,640 STARTED GLOBAL REGISTRATION 136 00:06:57,640 --> 00:07:00,960 TRIAL IN 2015 AND BROUGHT TO 137 00:07:00,960 --> 00:07:06,120 ODAC IN 2017 AND FIRST FDA 138 00:07:06,120 --> 00:07:09,040 APPROVAL IN CAR T IN LATE AUGUST 139 00:07:09,040 --> 00:07:11,000 AND IT WAS FIRST GENE THERAPY 140 00:07:11,000 --> 00:07:17,320 APPROVED IN US AND IN 2023 WE 141 00:07:17,320 --> 00:07:20,520 HAVE SIX CAR TS AND THEY ARE 142 00:07:20,520 --> 00:07:23,480 CONSIDERABLE AS WE KNOW AND MANY 143 00:07:23,480 --> 00:07:26,720 ARE WORKING ON AND PREINFUSED 144 00:07:26,720 --> 00:07:29,640 GENE THERAPY FOR THOSE THAT ARE 145 00:07:29,640 --> 00:07:33,320 CELL THERAPISTS AND THREE MORE 146 00:07:33,320 --> 00:07:33,920 POTENT 147 00:07:33,920 --> 00:07:38,120 POTENTIALLY COMING THIS YEAR 148 00:07:38,120 --> 00:07:40,760 USING ENGINEERS HEMOPOETIC STEM 149 00:07:40,760 --> 00:07:45,080 CELLS AND ON THE RIGHT YOU SEE 150 00:07:45,080 --> 00:07:47,520 EMILY WHITEHEAD 10 YEARS OUT 151 00:07:47,520 --> 00:07:50,400 POISED 17 YEAR OLD TALKING TO 152 00:07:50,400 --> 00:07:52,720 ALROEKER ON SET OF TODAY SHOW 153 00:07:52,720 --> 00:07:56,960 AND SHE HAS BECOME INTERNATIONAL 154 00:07:56,960 --> 00:07:59,400 FACE OF PEDIATRIC CELL THERAPY 155 00:07:59,400 --> 00:08:01,000 IN MANY WAYS AND IF YOU KNOW HER 156 00:08:01,000 --> 00:08:04,760 AND HER MOM THEY ARE AMAZING 157 00:08:04,760 --> 00:08:06,720 ADVOCATES FOR CAR T AND COMMENT 158 00:08:06,720 --> 00:08:07,880 QUICKLY THAT ONE IMPORTANT 159 00:08:07,880 --> 00:08:11,080 LESSON LEARNED EARLY ON WAS 160 00:08:11,080 --> 00:08:12,000 IMPORTANCE OF APPROPRIATE CELL 161 00:08:12,000 --> 00:08:13,960 MANUFACTURING AND VARIOUS WAYS 162 00:08:13,960 --> 00:08:16,720 TO GET TO THIS PATHWAY AND WAY 163 00:08:16,720 --> 00:08:18,920 YOU ACTIVATE T-CELLS MATTER AZ 164 00:08:18,920 --> 00:08:22,120 LOT AND SOME ACTIVATION MATRIX 165 00:08:22,120 --> 00:08:23,640 BEADS MOST OFTENLY USED ARE 166 00:08:23,640 --> 00:08:27,320 IMPORTANT IN GETTING THIS RIGHT 167 00:08:27,320 --> 00:08:29,680 ALLOWING T-CELL REPERTOIRE 168 00:08:29,680 --> 00:08:31,480 PRESERVATION AND CELLS THAT 169 00:08:31,480 --> 00:08:34,120 MAINTAINED WE LEARNED NOW EARLY 170 00:08:34,120 --> 00:08:36,960 T-CELL PHENOTYPE THAW NEED FOR 171 00:08:36,960 --> 00:08:38,400 REAL APPROPRIATE ACTION 172 00:08:38,400 --> 00:08:42,800 ESPECIALLY IN AAL AND EVERYTHING 173 00:08:42,800 --> 00:08:45,960 MATTERS AND IS NOT PREDICTABLE 174 00:08:45,960 --> 00:08:48,440 AND SERUM MATTERS AND ACTIVATION 175 00:08:48,440 --> 00:08:50,200 MATRIX MATTERS AND TIME AND 176 00:08:50,200 --> 00:08:51,720 CULTURE SHORTER THE BETTER AND 177 00:08:51,720 --> 00:08:53,480 WE ARE TALKING ABOUT SHORT AND 178 00:08:53,480 --> 00:08:55,960 WE WILL TALK ABOUT IT BRIEFLY 179 00:08:55,960 --> 00:08:58,800 AND MEMORY EARLY PHENOTYPES AND 180 00:08:58,800 --> 00:09:00,560 ALL ARE HARD TO PREDICT AND LACK 181 00:09:00,560 --> 00:09:03,040 OF POTENCY ASSAY THAT LET'S YOU 182 00:09:03,040 --> 00:09:08,480 SAY WHAT WILL HAPPEN IN THE 183 00:09:08,480 --> 00:09:08,960 PATI 184 00:09:08,960 --> 00:09:09,240 PATIENT. 185 00:09:09,240 --> 00:09:11,520 WE LOOK AT WHAT HAPPENS A MONTH 186 00:09:11,520 --> 00:09:12,760 LATER AND LEARN ABOUT POTENCY 187 00:09:12,760 --> 00:09:15,640 AND LIKE TO HAVE BETTER TESTS 188 00:09:15,640 --> 00:09:17,240 THAN THAT AND BRIEFLY COMMENTING 189 00:09:17,240 --> 00:09:19,040 ON A QUESTION I GET ASKED FROM 190 00:09:19,040 --> 00:09:21,640 TIME TO TIME THAT IS WHY IS 191 00:09:21,640 --> 00:09:24,640 PEDIATRIC ALL FIRST TARGET OF 192 00:09:24,640 --> 00:09:27,840 FDA APPROVAL AND STARTED OUT 193 00:09:27,840 --> 00:09:29,520 UNIVERSITY OF PENNSYLVANIA THREE 194 00:09:29,520 --> 00:09:31,240 PATIENTS TREATED WITH CLL 195 00:09:31,240 --> 00:09:33,280 IMPORTANT TO REMEMBER THAT AND 196 00:09:33,280 --> 00:09:35,480 WE OPENED ADULT AND PEDIATRIC 197 00:09:35,480 --> 00:09:37,880 ALL TRIALS THAT IS PEDIATRIC 198 00:09:37,880 --> 00:09:40,040 TRIAL THAT IS LITTLE ENGINE THAT 199 00:09:40,040 --> 00:09:42,440 COULD AND KEPT MOVING FORWARD 200 00:09:42,440 --> 00:09:44,920 AND KNOCK ON WOOD TERRIFIED TO 201 00:09:44,920 --> 00:09:47,080 SAY THIS KNOCK ON WOOD CLINICAL 202 00:09:47,080 --> 00:09:48,440 HOLD WENT FROM PHASE 1 STUDY 203 00:09:48,440 --> 00:09:51,360 THAT ENROLLED EVENTUALLY 72 204 00:09:51,360 --> 00:09:54,640 PATIENTS NOT REALLY A PHASE 1 205 00:09:54,640 --> 00:09:58,800 STUDY AND TO NO. VAR TIS TRIALS 206 00:09:58,800 --> 00:10:02,000 THAT LED TO FDA APPROVAL AND WE 207 00:10:02,000 --> 00:10:04,320 ARE DOING MANUFACTURING AND IND 208 00:10:04,320 --> 00:10:07,600 AT CHOC NOW AND EVERYBODY KNOWS 209 00:10:07,600 --> 00:10:11,240 ABOUT ELLI ANA TRIAL AND FIRST 210 00:10:11,240 --> 00:10:12,080 GLOBAL TRIAL AND MANY 211 00:10:12,080 --> 00:10:13,520 PARTICIPANTS IN THE AUDIENCE AND 212 00:10:13,520 --> 00:10:16,960 PURPOSE OF SHOWING THIS SLIDE IS 213 00:10:16,960 --> 00:10:19,880 SHOWING THIS SLIDE UPDATED DATA 214 00:10:19,880 --> 00:10:22,440 FROM ELIANA TRIAL GOING OUT AS 215 00:10:22,440 --> 00:10:25,400 FAR AS 60 MONTHS WITH 5 YEAR 216 00:10:25,400 --> 00:10:29,040 RELAPSE FREE SURVIVAL OF 44% AND 217 00:10:29,040 --> 00:10:31,800 MEDIAN RELAPSE RESURVIVAL OF 47 218 00:10:31,800 --> 00:10:35,440 MONTHS AND IS UPDATED DATA AND 219 00:10:35,440 --> 00:10:37,760 WHAT THINGS LIKE LIKE IN YOU 220 00:10:37,760 --> 00:10:40,280 FOLLOW PATIENTS LONGER AND SHOW 221 00:10:40,280 --> 00:10:42,600 ME 2 OR 3 YEAR DATA WHAT IT 222 00:10:42,600 --> 00:10:44,600 LOOKS LIKE AT YEAR 5 AND IS OUT 223 00:10:44,600 --> 00:10:46,960 NOW AND THANKS FOR A NUMBER OF 224 00:10:46,960 --> 00:10:49,480 PEOPLE WORKING ON THIS INCLUDING 225 00:10:49,480 --> 00:10:54,840 SHANNON AND TED ISSUE B CELL A- 226 00:10:54,840 --> 00:10:58,680 MRASHIA WITH CD19 CARS AND B 227 00:10:58,680 --> 00:11:01,200 CELL AMRASHIA IS IMPORTANT AND 6 228 00:11:01,200 --> 00:11:03,200 MONTHS RETROSPECTIVE STUDIES WE 229 00:11:03,200 --> 00:11:04,760 HAVE DONE AND MIKE WILL TALK TO 230 00:11:04,760 --> 00:11:06,760 YOU ABOUT THIS SO IMPORTANT THAT 231 00:11:06,760 --> 00:11:08,520 SHOWS THAT 6 MONTH MARK HAS 232 00:11:08,520 --> 00:11:10,800 VALIDITY IN ALL AND DOESN'T 233 00:11:10,800 --> 00:11:13,400 APPLY TO LYMPHOMA AND SHORTER 234 00:11:13,400 --> 00:11:17,680 INTENSE CARS AND CD28 CARS PRIOR 235 00:11:17,680 --> 00:11:20,720 TO LYMPHOMA HAVE GREAT EFFICACY 236 00:11:20,720 --> 00:11:23,360 AND PRESERVATION OF A GREAT CR 237 00:11:23,360 --> 00:11:25,880 THAT WE ARE LOOKING FOR AND 238 00:11:25,880 --> 00:11:28,680 ACHIEVING CR AND KEEPING 239 00:11:28,680 --> 00:11:30,560 PATIENTS THERE AND NECESSARY TO 240 00:11:30,560 --> 00:11:33,600 HAVE A 6 MONTH TIMEFRAME TO KEEP 241 00:11:33,600 --> 00:11:35,600 PATIENTS INTO REMISSION AND OWN 242 00:11:35,600 --> 00:11:37,000 EXPERIENCE AT CHOC SUPPORT STAFF 243 00:11:37,000 --> 00:11:39,360 AND IS ABSOLUTELY CELL TYPE 244 00:11:39,360 --> 00:11:41,160 DEPENDENT AND I WANT TO BE CLEAR 245 00:11:41,160 --> 00:11:44,640 ABOUT THAT AND HAPPENS TO BE FDA 246 00:11:44,640 --> 00:11:47,880 APPROVED THERAPY AVAILABLE TO US 247 00:11:47,880 --> 00:11:50,000 AND B MRASHIA FROM A RECENT 248 00:11:50,000 --> 00:11:52,880 TRIAL AND HALF PATIENTS REMAIN 249 00:11:52,880 --> 00:11:55,400 FROM B CELL AMRASHIA IF THERE AT 250 00:11:55,400 --> 00:11:59,360 A YEAR YOU ARE PROBABLY THERE AT 251 00:11:59,360 --> 00:12:00,600 YEAR 5 AND [INDISCERNIBLE] NO. 252 00:12:00,600 --> 00:12:03,560 I DON'T THINK SO. IT IS AN 253 00:12:03,560 --> 00:12:06,000 EITHER OR PROPOSITION FOR US AND 254 00:12:06,000 --> 00:12:10,000 WE ARE DEALING WITH LOTS OF 255 00:12:10,000 --> 00:12:11,600 PATIENTS WITH LONG TERM B CELL 256 00:12:11,600 --> 00:12:13,720 AMRASHIA THAT ARE GOOD NEWS IN 257 00:12:13,720 --> 00:12:14,400 REMISSION AND [INDISCERNIBLE] 258 00:12:14,400 --> 00:12:15,880 AND MIKE WILL TALK TO YOU ABOUT 259 00:12:15,880 --> 00:12:20,000 DATA. I WILL NOT. I WANT TO 260 00:12:20,000 --> 00:12:25,120 ACKNOWLEDGE TYPICAL FLOW MRD IS 261 00:12:25,120 --> 00:12:26,480 USEFUL AND DETERMINES WHETHER 262 00:12:26,480 --> 00:12:29,080 SUCCESS OR FAILURE AND WHETHER 263 00:12:29,080 --> 00:12:30,720 PRODUCT IS PAID FOR OR NEED TO 264 00:12:30,720 --> 00:12:33,240 PAY FOR PRODUCT STRONG OUTCOMES 265 00:12:33,240 --> 00:12:35,520 BASED AGREEMENT IN THE SHORT 266 00:12:35,520 --> 00:12:39,320 TERM AND NGSMRD ADDS INFORMATION 267 00:12:39,320 --> 00:12:42,360 IN TERMS OF PATIENTS IN FLOW AT 268 00:12:42,360 --> 00:12:44,760 MRD AND TELLS US GROUPS ARE 269 00:12:44,760 --> 00:12:46,960 DOING GREAT AND GROUPS THAT 270 00:12:46,960 --> 00:12:48,200 REALLY NEED FURTHER THERAPY AND 271 00:12:48,200 --> 00:12:50,280 ARGUMENT FROM A CURVE LIKE THIS 272 00:12:50,280 --> 00:12:53,320 IS NGS POSITIVE PATIENTS IN BLUE 273 00:12:53,320 --> 00:12:55,800 NEED TO GO TO TRANSPLANT AND AS 274 00:12:55,800 --> 00:12:57,520 I SAY GREEN CURVE HAS TO GO TO 275 00:12:57,520 --> 00:12:59,600 SCHOOL AND WILL BE DISAGREEMENT 276 00:12:59,600 --> 00:13:01,560 ABOUT THAT, THAT I RESPECT 277 00:13:01,560 --> 00:13:04,240 COMPLETELY. GETTING TO ISSUE OF 278 00:13:04,240 --> 00:13:05,320 TRANSPLANT, MOST PATIENTS STILL 279 00:13:05,320 --> 00:13:08,800 ARE NOT GOING TO TRANSPLANT 280 00:13:08,800 --> 00:13:12,680 AFTER CD19 AT CAR SHOP AND 281 00:13:12,680 --> 00:13:14,840 SELECTION BIAS IS THERE WE ARE 282 00:13:14,840 --> 00:13:16,440 BIASED AND HOW WE DO THINGS AND 283 00:13:16,440 --> 00:13:19,080 NO. 2 PEOPLE COME TO US TO AVOID 284 00:13:19,080 --> 00:13:20,760 TRANSPLANT I RUN THE TRANSPLANT 285 00:13:20,760 --> 00:13:22,640 PROGRAM AND THAT IS APPROACH WE 286 00:13:22,640 --> 00:13:24,080 HAVE TAKEN. WE HAD SUCCESS WITH 287 00:13:24,080 --> 00:13:26,880 THAT YOU KNOW HOW THIS WORKS WE 288 00:13:26,880 --> 00:13:37,360 MONITOR B CELL AMRASHIA AND 289 00:13:46,840 --> 00:13:49,520 USEFULNESS IN BONE MARROW. 290 00:13:49,520 --> 00:13:51,880 RELAPSE RATE IS QUITE LOW AND 291 00:13:51,880 --> 00:13:55,680 TOXICITY WE DEAL WITH CYTOKINE 292 00:13:55,680 --> 00:13:57,800 RELEASE SYNDROME AND WE MADE 293 00:13:57,800 --> 00:13:58,760 EARLY OBSERVATIONS ABOUT 294 00:13:58,760 --> 00:14:00,480 ELEVATED CYTOKINES AND THERE 295 00:14:00,480 --> 00:14:02,840 WERE MANY OF THEM. TWO THAT 296 00:14:02,840 --> 00:14:04,640 WERE STRIKINGLY ASSOCIATED WITH 297 00:14:04,640 --> 00:14:08,280 CHALLENGING OUTCOMES GOING TO 298 00:14:08,280 --> 00:14:11,320 INTENSIVE CARE UNIT AND 299 00:14:11,320 --> 00:14:16,320 INTERLEUKIN 6 STORY WAS 300 00:14:16,320 --> 00:14:19,120 INCREDIBLY IMPORTANT AND 301 00:14:19,120 --> 00:14:22,040 INTERFERON GAMA AND MEANS OF 302 00:14:22,040 --> 00:14:23,440 CONTROLLING CRS ON FLY ON 303 00:14:23,440 --> 00:14:25,040 WEDNESDAY AFTERNOON THROUGH 304 00:14:25,040 --> 00:14:27,000 ADVANCED TECH LOGICAL PROCESS 305 00:14:27,000 --> 00:14:29,640 NOTICING IL-6 IS HIGH AND ONLY 306 00:14:29,640 --> 00:14:31,640 CYTOKINE WE HAD A DRUG FOR AND 307 00:14:31,640 --> 00:14:33,320 WHY THAT HAPPENED AND EVERYTHING 308 00:14:33,320 --> 00:14:35,080 ELSE IS RETROSPECTIVELY 309 00:14:35,080 --> 00:14:37,480 UNDERSTOOD AND WE LEARNED WHY 310 00:14:37,480 --> 00:14:40,320 ABOUT MACROPHAGES AND DENDRITIC 311 00:14:40,320 --> 00:14:43,520 CELLS MATTER TO THIS AND 312 00:14:43,520 --> 00:14:44,920 INTERFERON GAMMA IS IMPORTANT 313 00:14:44,920 --> 00:14:46,880 BRINGING US TO ISSUE THAT 314 00:14:46,880 --> 00:14:50,320 PATIENTS WITH CRS HAS ACTIVATION 315 00:14:50,320 --> 00:14:51,560 CIN DROM AND DISCOVER THE IN 316 00:14:51,560 --> 00:14:54,560 LAST YEAR OR 2 AND KNOWN SINCE 317 00:14:54,560 --> 00:14:57,600 FIRST PATIENT AND IS TRUE AND 318 00:14:57,600 --> 00:15:00,760 WAY TO TREAT MS IS TREAT CRMS 319 00:15:00,760 --> 00:15:03,920 AND GREAT WORKING WITH LATER -- 320 00:15:03,920 --> 00:15:07,840 ASSOCIATED WITH CDC22 CARS TOESY 321 00:15:07,840 --> 00:15:09,520 REFRACTORY NOT ASSOCIATED WITH 322 00:15:09,520 --> 00:15:11,080 FEVER AND COMPLETE EDITING AND 323 00:15:11,080 --> 00:15:13,080 WE CAN LEARN A LOT FROM THE WORK 324 00:15:13,080 --> 00:15:16,560 AND MAS IS BASICALLY CRS OR CRS 325 00:15:16,560 --> 00:15:19,160 IS MAS AND WE NOW HAVE A TOOL 326 00:15:19,160 --> 00:15:21,520 THAT NEEDS LOTS OF STUDY THAT IS 327 00:15:21,520 --> 00:15:24,440 AVAILABLE TO US WITH PATIENTS 328 00:15:24,440 --> 00:15:27,280 WITH BAD TSOSIE REFRACTORY CMS 329 00:15:27,280 --> 00:15:28,800 AND LOTS TO LEARN ABOUT HOW WELL 330 00:15:28,800 --> 00:15:32,440 THIS WORKS AND TO KNOW THAT 331 00:15:32,440 --> 00:15:34,120 CYTOKINE IS ELEVATED MOST OF US 332 00:15:34,120 --> 00:15:36,400 ARE GETTING CYTOKINE PANELS AND 333 00:15:36,400 --> 00:15:37,880 THIS IS SOMETHING TO LEARN ABOUT 334 00:15:37,880 --> 00:15:41,360 AND SHANNON AND REGINA LOOK BACK 335 00:15:41,360 --> 00:15:44,440 AT TRENDS WE TREAT PATIENT 336 00:15:44,440 --> 00:15:45,680 OUTPATIENT WE ALWAYS HAVE. AND 337 00:15:45,680 --> 00:15:47,160 IF YOU LOOK AT TRENDS OVER TIME 338 00:15:47,160 --> 00:15:50,000 WHAT YOU ARE SEEING IS 80% OF 339 00:15:50,000 --> 00:15:51,800 PATIENTS BEING ADMITTED TO THE 340 00:15:51,800 --> 00:15:54,720 HOSPITAL AND 40% GOING TO ICU IN 341 00:15:54,720 --> 00:15:57,320 EARLY DAYS 2012 OR 2013 IS NOW 342 00:15:57,320 --> 00:15:59,560 DOWN TO HALF OF THE PATIENTS 343 00:15:59,560 --> 00:16:01,000 NEVER IN THE HOSPITAL FOR ONE 344 00:16:01,000 --> 00:16:02,880 MINUTE AND REASSURING PATIENTS 345 00:16:02,880 --> 00:16:06,080 IT IS OKAY TO NOT BE SICK AND 346 00:16:06,080 --> 00:16:10,040 DISEASE PATIENTS AND 12% GOING 347 00:16:10,040 --> 00:16:12,160 INTO ICU GREAT PROGRESS RELATED 348 00:16:12,160 --> 00:16:15,080 TO DISEASE BURDEN GETTING BETTER 349 00:16:15,080 --> 00:16:18,080 AT THIS 12% ARE REALLY SICK 350 00:16:18,080 --> 00:16:20,800 PATIENTS THAT WE WANT TO KNOW 351 00:16:20,800 --> 00:16:23,280 AND BRIEFLY ANDRÉ AND US WERE 352 00:16:23,280 --> 00:16:24,760 TALKING ABOUT EXCEPTIONAL 353 00:16:24,760 --> 00:16:27,920 RESPONDER PROJECT 475 PATIENTS 354 00:16:27,920 --> 00:16:30,240 HAVE BEEN TREATED AT CHOC AND 355 00:16:30,240 --> 00:16:32,800 INSTITUTION WE HAVE 60 PATIENTS 356 00:16:32,800 --> 00:16:37,600 5 OR MORE YEARS OUT WITHOUT 357 00:16:37,600 --> 00:16:38,880 THERAPY AND WE ARE TRYING TO 358 00:16:38,880 --> 00:16:42,080 UNDERSTAND AND REVERSE ENGINEER 359 00:16:42,080 --> 00:16:43,880 THAT AND PRODUCT CHARACTERISTICS 360 00:16:43,880 --> 00:16:46,440 THAT LEAD TO THAT AND LOOKING 361 00:16:46,440 --> 00:16:49,440 FORWARD I PICKED 2028 AND NEW 362 00:16:49,440 --> 00:16:51,160 PATIENT HOSPITAL TOWER IS BEING 363 00:16:51,160 --> 00:16:53,680 BUILT AT CHOC AND SEEMS A LONG 364 00:16:53,680 --> 00:16:55,360 DISTANCE AWAY AND KEEPS GETTING 365 00:16:55,360 --> 00:16:57,600 CLOSER AND CLOSER AND WORRY 366 00:16:57,600 --> 00:17:01,200 ABOUT AT PEDIATRIC ALL WILL IT 367 00:17:01,200 --> 00:17:04,280 BE ONLY OPTION AND WILL WE HAVE 368 00:17:04,280 --> 00:17:08,320 IT AND NOE VAR TIS IS COMPLETE 369 00:17:08,320 --> 00:17:09,680 STATEMENT AND IF YOU IMAGINE 370 00:17:09,680 --> 00:17:11,200 FUTURE MAKING THINGS DIFFERENTLY 371 00:17:11,200 --> 00:17:13,040 FOR OTHER INDICATIONS WILL THAT 372 00:17:13,040 --> 00:17:16,480 KEEP HUGE FACTORIES OPEN AND 373 00:17:16,480 --> 00:17:19,880 MORRIS PLANES AND STEIN TO TREAT 374 00:17:19,880 --> 00:17:22,000 PATIENTS? WHAT ARE OTHER 375 00:17:22,000 --> 00:17:23,400 CHOICES AND THERE ARE FOUR 376 00:17:23,400 --> 00:17:25,920 TRIALS ON HOLD NOW AND WILL SEE 377 00:17:25,920 --> 00:17:27,480 WHETHER THEY WILL PROCEED TO 378 00:17:27,480 --> 00:17:29,840 INDICATION IN PEDIATRICS AND BMS 379 00:17:29,840 --> 00:17:32,720 TRIAL HAS TAKEN A WHILE TO GET 380 00:17:32,720 --> 00:17:35,720 OFF GROUND IN A FULL WAY AND 381 00:17:35,720 --> 00:17:37,160 CAN'T PREDICT WHETHER THIS LICIS 382 00:17:37,160 --> 00:17:39,920 CELL WILL BE AN OPTION FOR US 383 00:17:39,920 --> 00:17:42,280 AND IS VERY EXCITING AND PEDS 384 00:17:42,280 --> 00:17:44,520 LYMPHOMA THAT IS 18 OR ABOVE AS 385 00:17:44,520 --> 00:17:46,960 FAR AS I CAN TELL AND WE DON'T 386 00:17:46,960 --> 00:17:48,800 HAVE THE PRODUCT YET AND WILL 387 00:17:48,800 --> 00:17:50,480 SOON AND THE CELL IS ADULT AND 388 00:17:50,480 --> 00:17:53,400 WILL TAKE PATIENTS MORE THAN 50 389 00:17:53,400 --> 00:17:55,080 KILOGRAMS THAT ARE ADULT SIZED 390 00:17:55,080 --> 00:17:58,560 AND MANUFACTURING I WILL COMMENT 391 00:17:58,560 --> 00:18:01,720 ON BRIEFLY AND NOE VAR TIS HAS 392 00:18:01,720 --> 00:18:03,920 TAKEN A STEP FORWARD IN 393 00:18:03,920 --> 00:18:05,120 MANUFACTURING USING T CHARGE 394 00:18:05,120 --> 00:18:07,800 PROCESS LOTS IS NOT KNOWN AND 395 00:18:07,800 --> 00:18:10,960 VAST MANUFACTURING COUPLE DAYS 396 00:18:10,960 --> 00:18:12,320 MANUFACTURING DOING RELEASE 397 00:18:12,320 --> 00:18:13,880 TAKES TIME NOT LIKE YOU GET 398 00:18:13,880 --> 00:18:15,800 CELLS BACK IN TWO DAYS THAT IS A 399 00:18:15,800 --> 00:18:17,600 STEP FORWARD AND YOU BELIEVE AS 400 00:18:17,600 --> 00:18:20,040 I DO LESS CELLS OUT OF THE BODY 401 00:18:20,040 --> 00:18:23,040 BETTER CELLS YOU GET AT END AND 402 00:18:23,040 --> 00:18:25,680 CHALLENGE IS LACK OF A POTENCY 403 00:18:25,680 --> 00:18:30,120 ASSAY THAT I MENTIONED AND 404 00:18:30,120 --> 00:18:34,720 NOTION IS MANUFACTURER STARTS IN 405 00:18:34,720 --> 00:18:41,440 LAB AND -- TECHNOLOGIES AND 406 00:18:41,440 --> 00:18:42,720 PRODIGY DEVICE IN SHOP AND USED 407 00:18:42,720 --> 00:18:45,560 IN VARIETY OF CLINICAL TRIALS 408 00:18:45,560 --> 00:18:48,040 AND DEVICE THAT I KNOW THAT 409 00:18:48,040 --> 00:18:50,200 HASN'T BEEN USED IN A PATIENT IS 410 00:18:50,200 --> 00:18:53,040 HEADING TOWARDS THAT AND THESE 411 00:18:53,040 --> 00:18:54,800 ALLOW POTENTIAL FOR POINT OF 412 00:18:54,800 --> 00:18:56,320 CARE THAT, AGAIN, MY PERSONAL 413 00:18:56,320 --> 00:19:00,280 OPINION WILL BE LIMITED TO BIG 414 00:19:00,280 --> 00:19:03,240 PLACES THAT HAVE STAFF AND 415 00:19:03,240 --> 00:19:04,640 PAPERWORK TO DO THIS TRIAL AND 416 00:19:04,640 --> 00:19:08,680 DON'T THINK HOSPITALS WILL USE 417 00:19:08,680 --> 00:19:10,080 PRODIGY ANYTIME SOON AND DON'T 418 00:19:10,080 --> 00:19:11,800 SEE THAT AND THAT IS MY PERSONAL 419 00:19:11,800 --> 00:19:13,960 LACK OF VISION AND LOVE THIS 420 00:19:13,960 --> 00:19:15,960 THOUGHT NONCANCER APPLICATIONS 421 00:19:15,960 --> 00:19:20,520 AND WE HAVE ZINTEGLO FROM 422 00:19:20,520 --> 00:19:22,640 BLUEBIRD AND SKY SEWNA FROM ALD 423 00:19:22,640 --> 00:19:25,280 AND FDA APPROVED AND WE WILL SEE 424 00:19:25,280 --> 00:19:28,640 SICKLE CELL PRODUCTS FROM 425 00:19:28,640 --> 00:19:30,000 [INDISCERNIBLE] AND BLUEBERG 426 00:19:30,000 --> 00:19:32,120 THIS YEAR AND IN FRONT OF THE 427 00:19:32,120 --> 00:19:33,680 FDA CAN'T JUDGE WHAT THEY WILL 428 00:19:33,680 --> 00:19:35,680 DO THAT WILL OPEN THAT TO ALL OF 429 00:19:35,680 --> 00:19:38,680 US AND THEY ARE GENE INSERTION 430 00:19:38,680 --> 00:19:41,720 THAT IS BLUEBERG PRODUCT USING 431 00:19:41,720 --> 00:19:43,560 VECTOR AND ACTUAL CRISPR GENE 432 00:19:43,560 --> 00:19:46,040 EDITING AND SURE THAT THE 433 00:19:46,040 --> 00:19:47,680 PRODUCT IS FIRST CRISPR CELL 434 00:19:47,680 --> 00:19:48,800 THERAPY PRODUCT THAT GETS ON TO 435 00:19:48,800 --> 00:19:50,960 THE MARKET AND WILL SEE IF THAT 436 00:19:50,960 --> 00:19:52,600 HAPPENS AND I WILL END WITH THIS 437 00:19:52,600 --> 00:19:54,960 THAT IS A DIAGRAM OF BILLIONS OF 438 00:19:54,960 --> 00:19:57,400 DOLLARS OF INVESTMENT GOING INTO 439 00:19:57,400 --> 00:19:59,480 CAR T DEVELOPMENT AND MESSAGE IS 440 00:19:59,480 --> 00:20:02,040 SIMPLE. WHERE ARE KIDS IN THIS? 441 00:20:02,040 --> 00:20:05,480 WE HAVE TO HOLD THESE 442 00:20:05,480 --> 00:20:07,000 ACCOUNTABLE HAVING PEDIATRIC 443 00:20:07,000 --> 00:20:08,040 PROGRAMS AND IS NOT ENOUGH TO 444 00:20:08,040 --> 00:20:10,160 HAVE A PIP THAT THEY HAVE NO 445 00:20:10,160 --> 00:20:12,160 INTENTION OF ACTUALLY COMPLETING 446 00:20:12,160 --> 00:20:16,200 TO KEEP EMA HAPPY AND PEDIATRIC 447 00:20:16,200 --> 00:20:18,000 QUESTIONS HAVE TO EFFECT WHAT WE 448 00:20:18,000 --> 00:20:19,880 DO FOR PATIENTS IN THE FUTURE 449 00:20:19,880 --> 00:20:21,120 AND INTERACTION IN THE COMPANIES 450 00:20:21,120 --> 00:20:22,920 TO PUSH THEM ON THIS AND WHAT 451 00:20:22,920 --> 00:20:24,280 YOU WILL DO FOR KIDS IN THE 452 00:20:24,280 --> 00:20:26,000 FUTURE AND WE GOT YOU THERE 453 00:20:26,000 --> 00:20:27,600 FIRST AND WHAT WE CAN DO FOR 454 00:20:27,600 --> 00:20:29,320 KIDS IN THE FUTURE AND WITH THAT 455 00:20:29,320 --> 00:20:32,640 I WILL THANK YOU VERY MUCH FOR 456 00:20:32,640 --> 00:20:39,040 YOUR TIME AND -- 457 00:20:39,040 --> 00:20:47,920 >> THANK YOU. I'M SHANNON FROM 458 00:20:47,920 --> 00:20:50,960 CHOC AND MY PLEASURE TO 459 00:20:50,960 --> 00:20:54,760 INTRODUCE NEXT SPEAKER PATRICK 460 00:20:54,760 --> 00:20:56,160 MCSWEENEY. I HAVE KNOWN SINCE 461 00:20:56,160 --> 00:20:59,120 HE WAS A TEENAGER. 9 YEARS AGO 462 00:20:59,120 --> 00:21:01,040 IS WHEN WE FIRST MET. PATRICK 463 00:21:01,040 --> 00:21:03,040 WILL TELL YOU HIS STORY THAT IS 464 00:21:03,040 --> 00:21:05,680 REALLY TRULY INSPIRATIONAL. 465 00:21:05,680 --> 00:21:09,640 WHAT I WANT TO TELL YOU IS IN 466 00:21:09,640 --> 00:21:11,640 INTRODUCING HIM IS I WON'T GO 467 00:21:11,640 --> 00:21:13,280 INTO HIS WHOLE STORY. THAT IS 468 00:21:13,280 --> 00:21:16,920 FOR HIM TO TELL. YOU WILL HEAR 469 00:21:16,920 --> 00:21:22,120 THAT HE HAS BEEN IS PARLT OF THE 470 00:21:22,120 --> 00:21:23,440 MEDICAL SYSTEM FOR MANY YEARS. 471 00:21:23,440 --> 00:21:25,800 WHEN HE WENT AWAY TO COLLEGE, HE 472 00:21:25,800 --> 00:21:27,800 DID NOT RUN FROM THAT. HE 473 00:21:27,800 --> 00:21:29,720 DIDN'T TRY TO GET AWAY. HE 474 00:21:29,720 --> 00:21:31,960 ACTUALLY WENT ALL IN TO GIVE 475 00:21:31,960 --> 00:21:34,160 BACK. AND TO BE PART OF THE 476 00:21:34,160 --> 00:21:36,840 IMPROVEMENT OF CARE OF KIDS WITH 477 00:21:36,840 --> 00:21:40,080 CANCER. WHEN HE STARTED COLLEGE 478 00:21:40,080 --> 00:21:42,760 HE BECAME INVOLVED IN A 479 00:21:42,760 --> 00:21:44,640 FUNDRAISING DANCE MARATHON THAT 480 00:21:44,640 --> 00:21:46,800 IS UL RAISE RED. HE WILL TALK 481 00:21:46,800 --> 00:21:48,720 ABOUT THAT A LITTLE BIT. HE 482 00:21:48,720 --> 00:21:52,840 WENT ON TO SERVE ON THE 483 00:21:52,840 --> 00:21:54,920 EXECUTIVE BOARD OF THAT AND 484 00:21:54,920 --> 00:21:58,080 BECAME A PATIENT CARE LIAISON 485 00:21:58,080 --> 00:22:00,440 COORDINATOR AND ACTIVITIES 486 00:22:00,440 --> 00:22:01,560 PUTTING ON FOR CHILDREN WITH 487 00:22:01,560 --> 00:22:03,240 CANCER AND FAMILIES AND HE 488 00:22:03,240 --> 00:22:05,600 GRADUATED FROM UNIVERSITY OF 489 00:22:05,600 --> 00:22:08,000 LOUISVILLE A FEW MONTHS AGO WITH 490 00:22:08,000 --> 00:22:10,080 BSN AND PASSED BOARDS AND WILL 491 00:22:10,080 --> 00:22:12,520 BE STARTING IN HIS NURSING 492 00:22:12,520 --> 00:22:14,560 CAREER VERY SOON GIVING BACK TO 493 00:22:14,560 --> 00:22:16,720 PATIENTS LIKE HIM. IT IS MY 494 00:22:16,720 --> 00:22:19,120 PLEASURE. I THINK THAT INSPIRED 495 00:22:19,120 --> 00:22:20,560 TITLE FOR THE CONFERENCE IS A 496 00:22:20,560 --> 00:22:23,520 GOOD ONE. I KNOW YOU WILL BE AS 497 00:22:23,520 --> 00:22:25,680 INSPIRED AS I HAVE BEEN BY HIM 498 00:22:25,680 --> 00:22:33,240 FOR NINE YEARS AND WELCOME, 499 00:22:33,240 --> 00:22:33,760 PATR 500 00:22:33,760 --> 00:22:34,000 PATRICK. 501 00:22:34,000 --> 00:22:34,440 >> [APPLAUSE]. 502 00:22:34,440 --> 00:22:44,800 >> JUST A MOMENT. 503 00:22:49,160 --> 00:22:50,920 >> ONLY THING MIGHT HAVE MISSED 504 00:22:50,920 --> 00:22:53,000 IS I INITIALLY TRIED TO RUN FROM 505 00:22:53,000 --> 00:22:55,560 EVERYTHING AND STARTED OFF 506 00:22:55,560 --> 00:22:58,000 COLLEGE AS A MECHANICAL 507 00:22:58,000 --> 00:22:59,480 ENGINEER. LOOK WHERE WE ARE NOW 508 00:22:59,480 --> 00:23:02,120 BECAUSE NOW I CAN SAY THAT I'M A 509 00:23:02,120 --> 00:23:06,040 REGISTERED NURSE. I HAVE 510 00:23:06,040 --> 00:23:06,960 PROFESSIONAL CREDIBILITY OF 511 00:23:06,960 --> 00:23:09,480 SPEAKING TODAY A LITTLE MORE 512 00:23:09,480 --> 00:23:13,920 THAN 18.5 YEARS BEING A 513 00:23:13,920 --> 00:23:15,200 PEDIATRIC ONCOLOGY PATIENT 514 00:23:15,200 --> 00:23:16,920 DIDN'T GIVE ME ENOUGH 515 00:23:16,920 --> 00:23:18,120 CREDIBILITY. BEFORE OFFICIALLY 516 00:23:18,120 --> 00:23:20,640 STARTING NO THE TO SOUND LIKE AN 517 00:23:20,640 --> 00:23:23,120 OSCAR SPEECH I HAVE TO THANK 518 00:23:23,120 --> 00:23:25,200 PEOPLE. DR. WONG FOR THE 519 00:23:25,200 --> 00:23:26,680 INVITATION AND DR. GRUPP AND 520 00:23:26,680 --> 00:23:28,280 ENTIRE TEAM THAT TOOK CARE OF ME 521 00:23:28,280 --> 00:23:31,000 AT CHOC AND NIH FOR ALLOWING ME 522 00:23:31,000 --> 00:23:34,320 TO SPEAK AND FINALLY MOST 523 00:23:34,320 --> 00:23:36,240 IMPORTANTLY MY MOTHER. 524 00:23:36,240 --> 00:23:39,040 SHE IS A NURSE HERSELF AND SHE 525 00:23:39,040 --> 00:23:40,960 UNDERSTANDS THE IMPORTANCE OF 526 00:23:40,960 --> 00:23:41,760 DOCUMENTATION AND KEEPING A 527 00:23:41,760 --> 00:23:46,040 RECORD OF EVENTS AND KEPT A 528 00:23:46,040 --> 00:23:46,600 2-DECADE LONG RECORD WHAT 529 00:23:46,600 --> 00:23:49,240 HAPPENED TO ME AND TALKING ABOUT 530 00:23:49,240 --> 00:23:51,120 CAR EXPERIENCES READING THAT IS 531 00:23:51,120 --> 00:23:55,440 HOW I GATHERED LOTS OF MY 532 00:23:55,440 --> 00:23:55,760 INFORMATION. 533 00:23:55,760 --> 00:23:58,880 IN FACT FAIR YEARS I RECEIVED 534 00:23:58,880 --> 00:24:04,360 CAR MADE FOR 123 PAGE WORD 535 00:24:04,360 --> 00:24:07,320 DOCUMENT HARD TO FIT INTO 15 536 00:24:07,320 --> 00:24:08,520 MINUTES WILL DO MY BEST AND 537 00:24:08,520 --> 00:24:11,320 APOLOGIZE IF I GO A LITTLE OVER. 538 00:24:11,320 --> 00:24:15,080 THANKS FOR SAVING ME TIME. MY 539 00:24:15,080 --> 00:24:20,440 STORY BEGAN IN APRIL 2004. I 540 00:24:20,440 --> 00:24:21,800 GOT STREP THROAT THREE TIMES AND 541 00:24:21,800 --> 00:24:26,120 MY MOM TOOK ME TO LOCAL 542 00:24:26,120 --> 00:24:28,200 PEDIATRICIANS OFFICE TO GET 543 00:24:28,200 --> 00:24:31,800 BLOOD DRAWN FROM THERE I WAS 544 00:24:31,800 --> 00:24:33,720 SENT TO CHILDREN'S HOSPITAL AND 545 00:24:33,720 --> 00:24:36,520 DIAGNOSED WITH ALL AT AGE OF 5. 546 00:24:36,520 --> 00:24:39,920 AFTER INITIAL DIAGNOSIS I BEGAN 547 00:24:39,920 --> 00:24:41,520 CHEMOTHERAPY RECEIVING 38 MONTHS 548 00:24:41,520 --> 00:24:45,960 OF IT AND COMPLETED 549 00:24:45,960 --> 00:24:48,960 CHEMOREJIMMEN IN 2007 NO THE 550 00:24:48,960 --> 00:24:54,080 BEFORE EXPERIENCING A CEREBRAL 551 00:24:54,080 --> 00:24:57,080 BLOOD CLOT AND PANCREATITIS AND 552 00:24:57,080 --> 00:24:59,840 AFTER BEING IN REMISSION FOR 4.5 553 00:24:59,840 --> 00:25:01,960 YEARS I RELAPSED FIRST TIME IN 554 00:25:01,960 --> 00:25:04,240 APRIL OF 2010 AND AFTER FIRST 555 00:25:04,240 --> 00:25:07,920 RELAPSE WE CONSULTED DOCTORS AT 556 00:25:07,920 --> 00:25:09,240 CINCINNATI CHILDREN'S TO GET 557 00:25:09,240 --> 00:25:11,080 OPINIONS ON IF I SHOULD RECEIVE 558 00:25:11,080 --> 00:25:13,320 A BONE MARROW TRANSPLANT OR 559 00:25:13,320 --> 00:25:15,520 RECEIVE MORE CHEMOTHERAPY. THEY 560 00:25:15,520 --> 00:25:18,080 RECOMMENDED I RECEIVE ADDITIONAL 561 00:25:18,080 --> 00:25:19,320 CHEMOTHERAPY DUE TO FACT IT WAS 562 00:25:19,320 --> 00:25:23,080 A LATE RELAPSE. I ENDURED 563 00:25:23,080 --> 00:25:27,200 ANOTHER 26 MONTHS OF 564 00:25:27,200 --> 00:25:33,840 CHEMOCOMPLETING SEC REJIMMEN IN 565 00:25:33,840 --> 00:25:34,200 2012. 566 00:25:34,200 --> 00:25:37,640 TIME SPENT IN SECOND REMISSION 567 00:25:37,640 --> 00:25:39,880 WAS SHORTER THAN THE FIRST AND 568 00:25:39,880 --> 00:25:42,080 RELAPSED A SECOND TIME AND 569 00:25:42,080 --> 00:25:47,720 KNOWING CHEMOTHERAPY WASN'T MY 570 00:25:47,720 --> 00:25:50,520 LONG-TERM SOLUTION WE WENT TO 571 00:25:50,520 --> 00:25:53,760 CINCINNATI FOR A BMT AND I WAS 572 00:25:53,760 --> 00:25:56,680 PREPPED WITH MORE CHEMOAND BODY 573 00:25:56,680 --> 00:25:58,000 RADIATION AND RECEIVED 574 00:25:58,000 --> 00:26:02,120 TRANSPLANT MAY 14TH, 2013 WITH 575 00:26:02,120 --> 00:26:04,600 MY OLDER BROTHER JOEY BEING A 576 00:26:04,600 --> 00:26:05,800 PERFECTLY MATCHED DONOR AND KEPT 577 00:26:05,800 --> 00:26:07,920 ME IN REMISSION FOR 8 MONTHS OR 578 00:26:07,920 --> 00:26:10,040 SO I RELAPSED FOR THE THIRD TIME 579 00:26:10,040 --> 00:26:12,280 IN MARCH OF 2014 AND FEELING AS 580 00:26:12,280 --> 00:26:16,400 THOUGH WE HAD RUN OUT OF OPTIONS 581 00:26:16,400 --> 00:26:18,080 CINCINNATI POINTED US IN 582 00:26:18,080 --> 00:26:20,000 DIRECTION OF CHOC AND 2019 583 00:26:20,000 --> 00:26:22,120 CLINICAL TRIAL GOING ON AND FEW 584 00:26:22,120 --> 00:26:23,720 WEEKS AFTER THIRD RELAPSE WE 585 00:26:23,720 --> 00:26:25,560 WERE OFFICIALLY ACCEPTED INTO 586 00:26:25,560 --> 00:26:30,600 THE CTL019 STUDY ON APRIL FIRST, 587 00:26:30,600 --> 00:26:32,600 2019 THAT WOULD HAVE SUCKED IF 588 00:26:32,600 --> 00:26:35,120 IT WAS AN APRIL FOOL'S JOKE AND 589 00:26:35,120 --> 00:26:39,960 IT WASN'T AND MOM AND DAD AND I 590 00:26:39,960 --> 00:26:42,440 FLEW TO PHILLY A FEW DAYS LATER 591 00:26:42,440 --> 00:26:44,720 AND HAD T-CELLS EXTRACTED APRIL 592 00:26:44,720 --> 00:26:47,600 EIGHTH AND RETURNED HOME ON 9TH 593 00:26:47,600 --> 00:26:49,480 T-CELL GROWTH WAS SEEN IN LAB BY 594 00:26:49,480 --> 00:26:53,000 MAY FIFTH AND ENTIRE FAMILY AND 595 00:26:53,000 --> 00:26:54,440 INCLUDING TWO BROTHERS FLEW 596 00:26:54,440 --> 00:26:58,120 BLACKING TO PHILLY JULY 27TH 597 00:26:58,120 --> 00:26:59,760 LATER THAT YEAR BETWEEN THESE 598 00:26:59,760 --> 00:27:01,760 DATES I WAS DIAGNOSED WITH TYPE 599 00:27:01,760 --> 00:27:04,080 1 DIABETES THAT WILL MAKE FOR 600 00:27:04,080 --> 00:27:05,720 COMPLICATIONS IN THE FUTURE 601 00:27:05,720 --> 00:27:08,320 COMING TO CYTOKINE STORM 602 00:27:08,320 --> 00:27:09,800 INFLAMMATION AND EFFECT IT'S 603 00:27:09,800 --> 00:27:13,640 CAUSED ON MY BLOOD TRIGGERS AND 604 00:27:13,640 --> 00:27:14,240 EFFECTS THAT [INDISCERNIBLE] 605 00:27:14,240 --> 00:27:14,920 WOULD CAUSE. 606 00:27:14,920 --> 00:27:17,760 I RECEIVED T-CELLS FIRST TIME 607 00:27:17,760 --> 00:27:23,760 AUGUST 25TH, 2014 AND I BECAME 608 00:27:23,760 --> 00:27:26,840 PATIENT NO. 34 AND WHAT I 609 00:27:26,840 --> 00:27:29,520 EXPERIENCED WASN'T TERRIBLE AND 610 00:27:29,520 --> 00:27:31,760 IN-PATIENT TWICE AND BOTH TIMES 611 00:27:31,760 --> 00:27:33,920 FOR TWO DAYS AND I WAS ALLOWED 612 00:27:33,920 --> 00:27:35,360 TO GO BACK TO SCHOOL IN PERSON 613 00:27:35,360 --> 00:27:39,520 AFTER A YEAR AND A HALF OF HOME 614 00:27:39,520 --> 00:27:43,080 SCHOOLING AND BEGAN MY SOPHOMORE 615 00:27:43,080 --> 00:27:44,480 YEAR AT HIGH SCHOOL IN 616 00:27:44,480 --> 00:27:46,640 SEPTEMBER. I HAD AN IPAD TO 617 00:27:46,640 --> 00:27:49,240 WORK ON AND INFORMATION WILL BE 618 00:27:49,240 --> 00:27:51,480 RELEVANT LATER IN THE SPEECH. 619 00:27:51,480 --> 00:27:54,120 NOVEMBER 4TH, 2014 NO T-CELLS 620 00:27:54,120 --> 00:27:57,200 WERE DETECTED AND B CELLS WITH 621 00:27:57,200 --> 00:27:59,200 CD19 WERE PRESENT AND THIS 622 00:27:59,200 --> 00:28:04,280 CHANGE REQUIRED MOM AND I FLY TO 623 00:28:04,280 --> 00:28:07,160 PHILLY NOVEMBER 9TH FOR A 624 00:28:07,160 --> 00:28:10,120 BOOSTER SHOT OF T-CELLS AND FLY 625 00:28:10,120 --> 00:28:13,120 HOME TO LOUISVILLE ON NOVEMBER 626 00:28:13,120 --> 00:28:17,880 21ST THIS BOOSTER HAD NO EFFECT. 627 00:28:17,880 --> 00:28:24,400 AFTER A FEW CONSULTS TOLD TO DO 628 00:28:24,400 --> 00:28:26,520 HUMANIZED CAR TRIAL. JANUARY 629 00:28:26,520 --> 00:28:30,840 26TH, 2015 BACK GETTING T-CELLS 630 00:28:30,840 --> 00:28:32,680 EXTRACTED FOR THE SECOND TIME WE 631 00:28:32,680 --> 00:28:36,400 WR BACK IN PHILLY MAY 17TH AND 632 00:28:36,400 --> 00:28:38,360 BY THAT THURSDAY 21ST, WE FOUND 633 00:28:38,360 --> 00:28:41,960 OUT I RELAPSED FOR THE 4TH TIME. 634 00:28:41,960 --> 00:28:43,400 FORTUNATELY WE WERE UP IN PHILLY 635 00:28:43,400 --> 00:28:46,920 AND I RECEIVED HUMANIZED CAR 636 00:28:46,920 --> 00:28:50,120 CELLS AS PLANNED MAY 26TH AND I 637 00:28:50,120 --> 00:28:53,400 BECAME PATIENT NO. 4 IN HUMANIZE 638 00:28:53,400 --> 00:28:56,360 THE CAR TRIAL AND I WAS 639 00:28:56,360 --> 00:28:59,280 IN-PATIENT FOR 4 DAYS AND BAF IN 640 00:28:59,280 --> 00:29:02,480 LOUISVILLE AFTER 31 DAYS ON JUNE 641 00:29:02,480 --> 00:29:04,200 16TH. I GOT DRIVER'S PERMIT AND 642 00:29:04,200 --> 00:29:08,320 WENT TO CAMP FOR A WEEK AND GOT 643 00:29:08,320 --> 00:29:11,760 5-WEEK T-CELLS DONE AT CAMP AND 644 00:29:11,760 --> 00:29:15,160 BROTHERS AND DAD AND I WENT TO 645 00:29:15,160 --> 00:29:18,680 SEE A SHOW -- A FRIEND OF MINE 646 00:29:18,680 --> 00:29:22,440 BATTLING ALL AND UNDERGOING CAR 647 00:29:22,440 --> 00:29:24,280 HIMSELF AND RECEIVED HIS 648 00:29:24,280 --> 00:29:26,720 TREATMENT IN CINCINNATI AND 649 00:29:26,720 --> 00:29:29,960 NEVER FULLY GOT HIM IN EMISSION. 650 00:29:29,960 --> 00:29:35,040 HE WAS BEN AND HE DIED AND WE 651 00:29:35,040 --> 00:29:41,360 WERE SAME AGE AND DIAGNOSIS AND 652 00:29:41,360 --> 00:29:46,200 HE DIDN'T MAKE IT. I DID. 653 00:29:46,200 --> 00:29:49,000 GETTING BACK TO CAR WE FLEW TO 654 00:29:49,000 --> 00:29:51,160 PHILLY SEPTEMBER 9TH I RECEIVED 655 00:29:51,160 --> 00:29:53,520 NOT ONLY FIRST BOOSTER DOSE OF 656 00:29:53,520 --> 00:29:55,720 HUMANIZED CELLS ON ELEVENTH AND 657 00:29:55,720 --> 00:30:00,240 FIRST BOOSTER DOSE OF HUMANIZED 658 00:30:00,240 --> 00:30:02,960 CELLS EVER GIVEN NO BLASTS WERE 659 00:30:02,960 --> 00:30:06,640 EVER EVIDENT IN MY BODY AS OF 660 00:30:06,640 --> 00:30:09,120 SEPTEMBER 7TH. CHEMOHAD NO 661 00:30:09,120 --> 00:30:10,760 EFFECT ON MY B CELLS AND WAS 662 00:30:10,760 --> 00:30:12,600 DECIDED MOVING FORWARD WHEN I 663 00:30:12,600 --> 00:30:15,120 GOT BOOSTER DOSES CONDITIONING 664 00:30:15,120 --> 00:30:16,520 CHEMONEED TODAY BE GIVEN. THAT 665 00:30:16,520 --> 00:30:19,320 IS WHAT HAPPENED. WHEN WE FLEW 666 00:30:19,320 --> 00:30:22,080 BACK TO PHILLY NOVEMBER 15TH AND 667 00:30:22,080 --> 00:30:24,160 CONDITIONING CHEMOSTARTED 16TH 668 00:30:24,160 --> 00:30:29,320 AND FINISHED 19TH AND SECOND 669 00:30:29,320 --> 00:30:33,440 HUMANIZED BOOSTER DOSE WAS 670 00:30:33,440 --> 00:30:37,640 ADMINISTERED NOVEMBER 9TH, 2015. 671 00:30:37,640 --> 00:30:41,200 WE SPENT THANKSGIVING AS A 672 00:30:41,200 --> 00:30:42,200 FAMILY BECAME A MEMORABLE 673 00:30:42,200 --> 00:30:44,000 EXPERIENCE FOR ALL OF US WE WERE 674 00:30:44,000 --> 00:30:47,000 SPENDING THANKSGIVING IN 675 00:30:47,000 --> 00:30:49,920 PHILADELPHIA AND WENT TO HARD 676 00:30:49,920 --> 00:30:52,320 ROCK CAFE FOR THE BIG MEAL. I 677 00:30:52,320 --> 00:30:54,040 HAD A CHEESEBURGER AND FRIES AND 678 00:30:54,040 --> 00:30:57,680 TWO DAYS LATER I TRIED FIRST 679 00:30:57,680 --> 00:30:59,640 PHILLY CHOOEZ STEAK. ALWAYS 680 00:30:59,640 --> 00:31:04,800 BEEN A PICKY EATER TOOK ME A 681 00:31:04,800 --> 00:31:07,560 WHILE B CELLS WERE ABSENT AS OF 682 00:31:07,560 --> 00:31:09,560 DECEMBER 21ST, GOOD NEWS MOM 683 00:31:09,560 --> 00:31:12,840 CAME TO ROOM MONTH LATER JANUARY 684 00:31:12,840 --> 00:31:15,080 23RD AND BEGAN TO SPEAK TO ME 685 00:31:15,080 --> 00:31:17,480 STARTING WITH THIS NEVER GETS 686 00:31:17,480 --> 00:31:21,480 ANY EASIER I CUT HER OFF AND I 687 00:31:21,480 --> 00:31:24,480 RELAPSED B CELLS ARE GOING SHE 688 00:31:24,480 --> 00:31:26,600 WAS CAUGHT OFF GUARD WHICH 689 00:31:26,600 --> 00:31:28,560 WASN'T THE CASE MY FRIEND MEGAN 690 00:31:28,560 --> 00:31:30,960 DIED THAT DAY I JUMPED TO 691 00:31:30,960 --> 00:31:33,600 CONCLUSION I RELAPSED BASED OFF 692 00:31:33,600 --> 00:31:36,120 FIRST 5 WORDS OUT OF HER MOUTH 693 00:31:36,120 --> 00:31:37,240 WILL TELL YOU SOMETHING NEXT 694 00:31:37,240 --> 00:31:40,440 VISIT TO PHILLY EARLY MARCH 695 00:31:40,440 --> 00:31:42,080 SEEING B CELL INDEED RETURNED 696 00:31:42,080 --> 00:31:44,720 AND DURING VISIT WITH DR. MAUDE 697 00:31:44,720 --> 00:31:47,240 ON 7TH I ASKED HER WHAT IF 698 00:31:47,240 --> 00:31:49,680 TREATMENT DIDN'T WORK? SHE 699 00:31:49,680 --> 00:31:51,440 COULDN'T GIVE DEFINITIVE ANSWER 700 00:31:51,440 --> 00:31:54,720 AND MOM BROUGHT UP PD1 TARGETING 701 00:31:54,720 --> 00:31:56,880 DRUGS AND DR. MAUDE SMILED AND 702 00:31:56,880 --> 00:31:59,760 EVENTUALLY HAD A TRIAL ON 703 00:31:59,760 --> 00:32:02,120 EFFECTIVENESS ON INHIBITORS TO 704 00:32:02,120 --> 00:32:05,760 COMBAT WITH T-CELLS TO COMBAT 705 00:32:05,760 --> 00:32:07,960 LUKEMIA AND CONVERSATION MARCH 706 00:32:07,960 --> 00:32:10,720 16TH 2016 I RECEIVED A BOOSTER 707 00:32:10,720 --> 00:32:12,800 T-CELL INFUSION GOING BACK TO 708 00:32:12,800 --> 00:32:14,840 SPEECH TO BRING UP A POINT THAT 709 00:32:14,840 --> 00:32:17,520 MY SCHOOL USED IPADS I WAS 710 00:32:17,520 --> 00:32:18,840 FACETIMING IN U.S. HISTORY CLASS 711 00:32:18,840 --> 00:32:23,720 AS I RECEIVED 6TH TOTAL T-CELL 712 00:32:23,720 --> 00:32:25,800 INFUSION. DR. GRUPP AS HE 713 00:32:25,800 --> 00:32:27,400 PUSHED CELL IN MADE QUICK REMARK 714 00:32:27,400 --> 00:32:30,640 HE IS LEARNING HISTORY AND 715 00:32:30,640 --> 00:32:32,280 MAKING HISTORY. 716 00:32:32,280 --> 00:32:34,160 FAST FORWARD 6 MONTHS TO 717 00:32:34,160 --> 00:32:36,720 SEPTEMBER 2016 AND I RECEIVED A 718 00:32:36,720 --> 00:32:39,920 BONE MARROW BIOPSY IN LP AND 719 00:32:39,920 --> 00:32:41,960 RESULTS CAME BACK AND FOUND OUT 720 00:32:41,960 --> 00:32:44,800 I RELAPSED FOR FIFTH TIME AND 721 00:32:44,800 --> 00:32:48,160 COMMENT WAS I'M DISAPPOINTED BUT 722 00:32:48,160 --> 00:32:52,160 NOT SURPRISED. 723 00:32:52,160 --> 00:32:53,880 I SHOULDN'T BE EXPECTED TO 724 00:32:53,880 --> 00:32:56,960 RELAPSE WITH CANS ERR WHEN I'M 725 00:32:56,960 --> 00:32:58,600 17 AND SHOULDN'T BE EXPECTING 726 00:32:58,600 --> 00:32:59,880 TREATMENTS TO FAIL AND WHEN 727 00:32:59,880 --> 00:33:01,600 COMES TO CANCER BEING SO 728 00:33:01,600 --> 00:33:03,440 CONDITIONED TO RELAPSING ALL I 729 00:33:03,440 --> 00:33:07,480 CAN SAY IS I'M SDPOIBTED IS 730 00:33:07,480 --> 00:33:12,720 REMARKABLY HORRIBLE. 731 00:33:12,720 --> 00:33:14,680 MY T-CELLS WERE COLLECTED FOR 732 00:33:14,680 --> 00:33:17,200 THIRD TIME I WAS BACK TO SCHOOL 733 00:33:17,200 --> 00:33:20,000 PLAYING BASKETBALL SPENDING TIME 734 00:33:20,000 --> 00:33:22,120 WITH FRIENDS AND SOMETHING A 17 735 00:33:22,120 --> 00:33:24,240 YEAR OLD SHOULD BE DOING AND 736 00:33:24,240 --> 00:33:26,800 BACK IN PHILLY BY 6TH AND 737 00:33:26,800 --> 00:33:29,600 CONDITIONING STARTED ON 7TH AND 738 00:33:29,600 --> 00:33:33,080 -- I WAS ADMITTED TO 3 NORTH 739 00:33:33,080 --> 00:33:36,080 WITH FEVER ON 18TH EXPERIENCING 740 00:33:36,080 --> 00:33:38,160 WORST CYTOKINE STORM IN 7 DOSES 741 00:33:38,160 --> 00:33:40,800 OF T-CELLS I RECEIVED UP TO THIS 742 00:33:40,800 --> 00:33:43,720 POINT AND EXPERIENCED NAUSHIA 743 00:33:43,720 --> 00:33:49,120 DRIVE HEAVING 103° FEVERS 744 00:33:49,120 --> 00:33:50,360 VIGOROUS SHAKING AND CHILLING 745 00:33:50,360 --> 00:33:53,800 AND TYPE 1 DIABETIC EXPERIENCED 746 00:33:53,800 --> 00:33:56,920 SEVERAL BLOOD SUGAR ISSUES TOUGH 747 00:33:56,920 --> 00:33:58,200 TO FIND BALANCE CONSIDER 748 00:33:58,200 --> 00:33:59,440 INFLAMMATION WOULD RAISE SUGARS 749 00:33:59,440 --> 00:34:02,120 WITH LACK OF FOOD INTAKE 750 00:34:02,120 --> 00:34:04,800 DECREASE MY INSULIN. OUT OF THE 751 00:34:04,800 --> 00:34:07,320 HOSPITAL ON 23RD AND MOM AND I 752 00:34:07,320 --> 00:34:10,000 EXPERIENCED SECOND THANKSGIVING 753 00:34:10,000 --> 00:34:14,400 IN A ROW FOR THE THIRD TIME. 754 00:34:14,400 --> 00:34:16,920 THIS TIME DAD AND BROTHERS 755 00:34:16,920 --> 00:34:19,280 WEREN'T ABLE TO JOIN US. I WANT 756 00:34:19,280 --> 00:34:22,120 TO BE HOME FOR CHRISTMAS. 757 00:34:22,120 --> 00:34:23,760 THANKFULLY MY MOM AND I WERE 758 00:34:23,760 --> 00:34:25,440 ABLE TO HAVE SOME FUN THE 759 00:34:25,440 --> 00:34:27,080 FOLLOWING DAY ON 28TH AND I WAS 760 00:34:27,080 --> 00:34:30,400 ABLE TO GO TO PACKERS EAGLES 761 00:34:30,400 --> 00:34:32,360 MONDAY NIGHT FOOTBALL GAME. FOR 762 00:34:32,360 --> 00:34:34,200 EAGLES FANS, I WAS ROOTING FOR 763 00:34:34,200 --> 00:34:37,080 THE PACKERS THEY ARE KIND OF MY 764 00:34:37,080 --> 00:34:40,160 TEAM IRONIC PART WE GOT TICKETS 765 00:34:40,160 --> 00:34:41,800 FROM EAGLES ORGANIZATION. 766 00:34:41,800 --> 00:34:44,120 SO, I COULDN'T BE WEARING 767 00:34:44,120 --> 00:34:47,000 PACKERS GEAR WHEN YOU ARE GOING 768 00:34:47,000 --> 00:34:49,320 ON THE SIDE LINE BEFORE THE GAME 769 00:34:49,320 --> 00:34:51,440 MEETING THE EAGLES PRESIDENT AND 770 00:34:51,440 --> 00:34:54,800 GETTING PHOTOS I WORE A GREEN 771 00:34:54,800 --> 00:34:57,800 PACKERS HOODIE THREW A GREEN 772 00:34:57,800 --> 00:35:00,520 EAGLES SHIRT OVER IT GOT PREGAME 773 00:35:00,520 --> 00:35:01,720 SIDELINE EXPERIENCE AND 774 00:35:01,720 --> 00:35:04,760 PROCEEDED TO TAKE EAGLES SHIRT 775 00:35:04,760 --> 00:35:06,960 OFF GETTING TO SEATS FIRST ROW 776 00:35:06,960 --> 00:35:09,360 50 YARD LINE AND FANS BEHIND US 777 00:35:09,360 --> 00:35:11,400 WERE NOT HAPPY WITH ME AND 778 00:35:11,400 --> 00:35:14,440 PACKERS WON SO I HAD A GOOD 779 00:35:14,440 --> 00:35:14,640 TIME. 780 00:35:14,640 --> 00:35:17,040 VERY NEXT DAY ON 28TH I RECEIVED 781 00:35:17,040 --> 00:35:19,360 KEY TRUTH TO THE FIRST TIME P. 782 00:35:19,360 --> 00:35:21,680 D1 INHIBITOR DR. MAUDE TALKED 783 00:35:21,680 --> 00:35:24,400 ABOUT A LITTLE OVER 8 MONTHS 784 00:35:24,400 --> 00:35:25,960 PRIOR. DR. MAUDE SPECIFIED IT 785 00:35:25,960 --> 00:35:28,640 IS SUCCESSFUL IN TREATING LUNG 786 00:35:28,640 --> 00:35:31,680 CANCER AND MELANOMA BUT WANT 787 00:35:31,680 --> 00:35:33,880 CONCRETE DATA WITH LEUKEMIA 788 00:35:33,880 --> 00:35:35,440 REGARDING EFFECTIVENESS AND 789 00:35:35,440 --> 00:35:38,080 EXPERIENCED NO SIDE-EFFECTS FROM 790 00:35:38,080 --> 00:35:40,360 INFUSION DOWN 12 POUNDS FROM 791 00:35:40,360 --> 00:35:42,480 INITIAL CYTOKINE STORM AS OF 792 00:35:42,480 --> 00:35:45,560 NOVEMBER 30TH ISSUE FOR ME FOR 793 00:35:45,560 --> 00:35:47,080 THAT WAS WEIGHT LOSS RESET 794 00:35:47,080 --> 00:35:49,200 PHYSICAL STRENGTH AND STAMINA 795 00:35:49,200 --> 00:35:52,160 MAKING BASKETBALL THAT WINTER 796 00:35:52,160 --> 00:35:54,120 DIFFICULT DIDN'T SEEM LIKE A 797 00:35:54,120 --> 00:35:56,560 MINOR ISSUE FOR ME BUT IT WAS 798 00:35:56,560 --> 00:35:58,000 BIG AND SPORT AND SOCIAL 799 00:35:58,000 --> 00:36:00,520 INTERACTION WITH FRIENDS MADE ME 800 00:36:00,520 --> 00:36:03,360 FEEL NORMAL AND SUPPORTED WISH 801 00:36:03,360 --> 00:36:07,320 TO BE HOME BEFORE CHRISTMAS CAME 802 00:36:07,320 --> 00:36:11,800 TRUE HOME BY 20TH AND BACK IN 803 00:36:11,800 --> 00:36:16,480 PHILLY STARTING CHEMO-6TH 804 00:36:16,480 --> 00:36:18,480 RECEIVED 4TH BOOSTER AND MY 805 00:36:18,480 --> 00:36:21,240 FIFTH BOOSTER TOTAL AND BY THIS 806 00:36:21,240 --> 00:36:24,720 POINT THERE WAS SMALL AMOUNT OF 807 00:36:24,720 --> 00:36:27,080 T-CELLS EVEN BEFORE BOOSTER DR. 808 00:36:27,080 --> 00:36:29,360 MAUDE EXPLAINING TO US IT WAS 809 00:36:29,360 --> 00:36:31,440 MOST PROBABLE CAUSE OF T-CELL 810 00:36:31,440 --> 00:36:34,360 PERSISTENCE WITH THAT IN MIND I 811 00:36:34,360 --> 00:36:37,040 RECEIVED ANOTHER DOSE TWO WEEKS 812 00:36:37,040 --> 00:36:40,400 LATER AND WAS BACK HOME ON 28TH 813 00:36:40,400 --> 00:36:43,840 I WAS RECEIVING EVERY 4 WEEKS 814 00:36:43,840 --> 00:36:45,600 AFTER THIS TOLD EACH APPOINTMENT 815 00:36:45,600 --> 00:36:47,880 IN JULY THAT EACH DOSE INCREASES 816 00:36:47,880 --> 00:36:49,240 COMPLICATIONS IT WAS DOING WELL 817 00:36:49,240 --> 00:36:50,640 FOR ME I CONTINUE TODAY RECEIVE 818 00:36:50,640 --> 00:36:53,680 IT EVERY 4 WEEKS AND RECEIVED 819 00:36:53,680 --> 00:36:55,680 13TH DOSE OF IT OCTOBER 13TH. 820 00:36:55,680 --> 00:36:59,120 AFTER THAT, I BEGAN TO 821 00:36:59,120 --> 00:37:00,560 EXPERIENCE AUTO IMMUNE 822 00:37:00,560 --> 00:37:02,720 COMPLICATIONS WE HAD BEEN WARNED 823 00:37:02,720 --> 00:37:05,600 ABOUT IN JULY AND OCTOBER 21ST I 824 00:37:05,600 --> 00:37:09,360 EXPERIENCED SEVERE GI ISSUES 825 00:37:09,360 --> 00:37:11,200 VOMITING EVERY DAY NAUSEOUS AND 826 00:37:11,200 --> 00:37:13,720 QUICKLY FILLING UP WAKING UP TO 827 00:37:13,720 --> 00:37:16,280 VOMIT HAVING DIARRHEA AND NO 828 00:37:16,280 --> 00:37:17,800 APPETITE AND KEEP IN MIND PRIOR 829 00:37:17,800 --> 00:37:21,920 TO EFFECTS I WAS 65 KILOS AND I 830 00:37:21,920 --> 00:37:23,520 GOT SCOPED ON NOVEMBER 21ST WITH 831 00:37:23,520 --> 00:37:26,080 A SCOPE DETECTING EARLY STAGES 832 00:37:26,080 --> 00:37:31,600 OF COLITIS IN INTESTINES COLITIS 833 00:37:31,600 --> 00:37:32,520 IS SIDE EFFECT OF 834 00:37:32,520 --> 00:37:33,840 [INDISCERNIBLE] AND DUE TO 835 00:37:33,840 --> 00:37:35,200 VOMITING THAT HAPPENED OVER 836 00:37:35,200 --> 00:37:37,320 COURSE OF PREVIOUS MONTH AND BY 837 00:37:37,320 --> 00:37:40,280 DECEMBER 1ST, 6 WEEKS LATER I 838 00:37:40,280 --> 00:37:43,680 WAS DOWN 9 KILOS, 56.1 AND GOOD 839 00:37:43,680 --> 00:37:46,200 NEWS I DIDN'T HAVE TO GET MORE 840 00:37:46,200 --> 00:37:49,840 KEY TRIDA DR. MAUDE PLANNED TO 841 00:37:49,840 --> 00:37:51,600 STOP IT AT END OF DECEMBER 842 00:37:51,600 --> 00:37:53,120 ANYWAY. IT WAS DISCONTINUED A 843 00:37:53,120 --> 00:37:55,360 FEW WEEKS EARLIER THAN EXPECTED. 844 00:37:55,360 --> 00:37:57,480 NOW, THREE WEEKS AFTER THE SCOPE 845 00:37:57,480 --> 00:38:01,560 ON DECEMBER 13TH, BONE MARROW LP 846 00:38:01,560 --> 00:38:03,360 AND VERY IMPORTANT MILESTONE IN 847 00:38:03,360 --> 00:38:06,560 CAR PROGRAM MOVED INTO LONG-TERM 848 00:38:06,560 --> 00:38:08,800 PROTOCOL IN THREE YEARS I HAD 849 00:38:08,800 --> 00:38:11,800 BEEN RECEIVING CAR. HUGE 850 00:38:11,800 --> 00:38:14,440 MILESTONE REACHED FEW DAYS LATER 851 00:38:14,440 --> 00:38:17,280 HIT WITH NEWS THAT MRD RESULTS 852 00:38:17,280 --> 00:38:19,600 WERE INCONCLUSIVE ASKED TO FLY 853 00:38:19,600 --> 00:38:23,080 TO PHILLY JANUARY 23RD 2018 854 00:38:23,080 --> 00:38:26,640 REPEAT BONE MARROW ON 4TH AND 855 00:38:26,640 --> 00:38:28,720 STARTED ENGINEERING CLASSES NEXT 856 00:38:28,720 --> 00:38:31,040 WEEK STARTING 2 EIGHTH. I KNEW 857 00:38:31,040 --> 00:38:32,480 HOW LONG IT TOOK FOR RESULTS TO 858 00:38:32,480 --> 00:38:35,960 GET BACK AND LIVED BY MYSELF FOR 859 00:38:35,960 --> 00:38:37,720 MY FRESHMAN YEAR THIS IS 860 00:38:37,720 --> 00:38:40,280 IMPORTANT MY MOM SHOULD HAVE 861 00:38:40,280 --> 00:38:42,240 CALLED ME SOMETIME THAT WEEK 862 00:38:42,240 --> 00:38:44,560 TELLING ME I WAS IN REMISSION 863 00:38:44,560 --> 00:38:46,600 SHE WOULD NEVER CALL ME WITH BAD 864 00:38:46,600 --> 00:38:47,960 NEWS KNOWING I WAS BY MYSELF AND 865 00:38:47,960 --> 00:38:50,200 SHE DIDN'T CALL. I HAD MY 866 00:38:50,200 --> 00:38:52,800 ANSWER WITH HER RESULTS BONE 867 00:38:52,800 --> 00:38:54,840 MARROW BEFORE SHE EVEN TOLD ME 868 00:38:54,840 --> 00:38:56,920 AND I WENT HOME FRIDAY AFTER 869 00:38:56,920 --> 00:38:58,440 CLASS FIRST QUESTION OUT OF MY 870 00:38:58,440 --> 00:39:01,000 MOUTH WAS I'M GUESSING I 871 00:39:01,000 --> 00:39:05,000 RELAPSED SHE NODDED AND SHOOK 872 00:39:05,000 --> 00:39:07,720 HEAD YES AND I MADE LEMONADE OUT 873 00:39:07,720 --> 00:39:10,080 OF LEMONS WITH INFORMATION AND 874 00:39:10,080 --> 00:39:13,960 MADE VIDEO ANNOUNCING RELAPSE IN 875 00:39:13,960 --> 00:39:16,160 EARLY FEBRUARY FOR A DANCE 876 00:39:16,160 --> 00:39:18,600 MARATHON RAISE RED THAT RAISES 877 00:39:18,600 --> 00:39:20,720 MONEY FOR PEDIATRIC CANCER AND 878 00:39:20,720 --> 00:39:25,480 USED VIDEO TO FUNDRAISE FOR 879 00:39:25,480 --> 00:39:28,440 ORGANIZATION SETTING IT TO EARN 880 00:39:28,440 --> 00:39:31,240 $5,000 AND ACHIEVED GOAL IN LESS 881 00:39:31,240 --> 00:39:35,640 THAN 24 HOURS AND MADE SECOND 882 00:39:35,640 --> 00:39:38,000 VIDEO LETTING PEOPLE KNOW I WAS 883 00:39:38,000 --> 00:39:40,840 INCREASING IT TO $25,000. WENT 884 00:39:40,840 --> 00:39:41,840 FROM NIGHT OF 23RD TO NOON ON 885 00:39:41,840 --> 00:39:43,840 24TH AND ASPECT OF HOW THIS IS 886 00:39:43,840 --> 00:39:45,120 IMPORTANT IS I WAS SUPPOSED TO 887 00:39:45,120 --> 00:39:47,800 BE BACK UP IN PHILLY ON 18TH 888 00:39:47,800 --> 00:39:50,080 AFTER WHAT I ACCOMPLISHED I WAS 889 00:39:50,080 --> 00:39:52,720 NOT MISSING 18 HOUR DANCE 890 00:39:52,720 --> 00:39:54,240 MARATHON. I ASKED DR. MAUDE IF 891 00:39:54,240 --> 00:39:56,160 I COULD PUSH ARRIVING TO PHILLY 892 00:39:56,160 --> 00:39:58,440 BACK A WEEK. SHE AGREED. 893 00:39:58,440 --> 00:40:00,680 WHEN I LEFT FOR PHILLY ON 2 894 00:40:00,680 --> 00:40:03,040 FIFTH I LEFT ALL SMILES I 895 00:40:03,040 --> 00:40:04,560 EXPERIENCED THE DANCE MARATHON 896 00:40:04,560 --> 00:40:07,920 FOR FIRST TIME AND RAISED OVER 897 00:40:07,920 --> 00:40:11,200 $32,000 FOR PEDIATRIC CANCER AND 898 00:40:11,200 --> 00:40:12,040 BLOOD DISEASES AND COMBINATION 899 00:40:12,040 --> 00:40:16,240 OF HUMANIZED CELLS AND KEY 900 00:40:16,240 --> 00:40:18,160 TREEDA KEEPING ME IN REMISSION I 901 00:40:18,160 --> 00:40:20,040 RECEIVED CELLS ONE MORE TIME AND 902 00:40:20,040 --> 00:40:22,760 USED TREATMENT AS BRIDGE TO 903 00:40:22,760 --> 00:40:25,040 SECOND [INDISCERNIBLE] BACK IN 904 00:40:25,040 --> 00:40:26,320 CINCINNATI RECEIVED 9TH AND 905 00:40:26,320 --> 00:40:29,200 FINAL DOSE OF CAR ON MARCH FIFTH 906 00:40:29,200 --> 00:40:33,720 2019 NEED FOR THIS BECAME MORE 907 00:40:33,720 --> 00:40:37,000 EVIDENT WHEN DAY 28 BONE MARROW 908 00:40:37,000 --> 00:40:39,160 STILL REVEALED B CELLS EVEN 909 00:40:39,160 --> 00:40:40,920 AFTER CHEMOAND FIRST TIME IT 910 00:40:40,920 --> 00:40:44,200 HAPPENED BY DAY 28 WHEN 911 00:40:44,200 --> 00:40:45,600 RECEIVING CONDITIONING 912 00:40:45,600 --> 00:40:48,720 CHEMOPRIOR TO T-CELL INFUSION 913 00:40:48,720 --> 00:40:51,160 AFTER T-CELLS I RECEIVED SECOND 914 00:40:51,160 --> 00:40:54,120 BMT MAY 15TH 2018 AND BEEN IN 915 00:40:54,120 --> 00:40:56,440 REMISSION EVER SINCE AND 916 00:40:56,440 --> 00:40:58,080 APPROACHING 5 YEAR MARK THIS MAY 917 00:40:58,080 --> 00:41:00,840 AND MARK I NEVER HIT SINCE FIRST 918 00:41:00,840 --> 00:41:03,560 DIAGNOSED IN 2004 AND TO SAY I'M 919 00:41:03,560 --> 00:41:05,080 ECSTATIC IS AN UNDERSTATEMENT. 920 00:41:05,080 --> 00:41:07,760 WHILE THAT CONCLUDES MY HISTORY 921 00:41:07,760 --> 00:41:09,200 OF TREATMENT AND OF CAR NOW IS 922 00:41:09,200 --> 00:41:12,120 WHERE I EXPAND UPON WHAT CAN BE 923 00:41:12,120 --> 00:41:13,400 DONE TO IMPROVE CLINICAL TRIALS 924 00:41:13,400 --> 00:41:15,960 IN THE FUTURE. BEST WAY FOR US 925 00:41:15,960 --> 00:41:17,880 AS DOCTORS AND CAREGIVERS TO DO 926 00:41:17,880 --> 00:41:21,040 THIS IS BY HEAVILY FOCUSING ON 927 00:41:21,040 --> 00:41:22,760 PSYCHOSOCIAL ASPECT OF CARE 928 00:41:22,760 --> 00:41:26,880 ESPECIALLY IN CLINICAL TRIALS. 929 00:41:26,880 --> 00:41:28,720 [INDISCERNIBLE] IS STUDYING 930 00:41:28,720 --> 00:41:31,000 LIMITED INFORMATION AVAILABLE 931 00:41:31,000 --> 00:41:31,960 ABOUT PSYCHOSOCIAL ASPECT OF 932 00:41:31,960 --> 00:41:33,720 CARE AND FELT SHE WAS A GOOD 933 00:41:33,720 --> 00:41:35,480 RESOURCE TO UTILIZE WHEN 934 00:41:35,480 --> 00:41:36,720 ADDRESSING THIS THEME TODAY. 935 00:41:36,720 --> 00:41:39,760 SHE PROVIDED ME WITH TWO 936 00:41:39,760 --> 00:41:41,760 ARTICLES TO HELP SPUR FOLLOWING 937 00:41:41,760 --> 00:41:43,240 TRAINS OF THOUGHT. THE WHOLE 938 00:41:43,240 --> 00:41:45,000 REASON I WAS ABLE TO GET THROUGH 939 00:41:45,000 --> 00:41:47,200 CAR TREATMENT FOR FOUR YEARS BY 940 00:41:47,200 --> 00:41:49,520 FOUR RELAPSES DURING THOSE YEARS 941 00:41:49,520 --> 00:41:51,800 IS BECAUSE OF HOW WELL SUPPORTED 942 00:41:51,800 --> 00:41:53,760 I WAS THROUGH TREATMENT AND 943 00:41:53,760 --> 00:41:56,800 POSITIVE EXPERIENCES THAT I 944 00:41:56,800 --> 00:41:58,760 RECEIVED THROUGH TREATMENT. 945 00:41:58,760 --> 00:42:01,360 SURE. I WAS OVER 650 MILES AWAY 946 00:42:01,360 --> 00:42:05,960 FROM HOME IN LOUISVILLE BUT HAD 947 00:42:05,960 --> 00:42:08,920 FAMILY WILLING TO DRIVE TO 948 00:42:08,920 --> 00:42:10,720 PHILLY TO SPEND THANKSGIVING 949 00:42:10,720 --> 00:42:12,600 WITH ME AND MY MOM AND 950 00:42:12,600 --> 00:42:14,800 THROUGHOUT TREATMENT EVEN IF NOT 951 00:42:14,800 --> 00:42:16,760 GOING THROUGH SAME TREATMENT AND 952 00:42:16,760 --> 00:42:18,360 FRIENDS LIKE BEN AND MEGAN AND I 953 00:42:18,360 --> 00:42:21,000 HAD FRIENDS IN SCHOOL THAT WOULD 954 00:42:21,000 --> 00:42:23,240 FACETIME ME DURING CLASS KEEPING 955 00:42:23,240 --> 00:42:24,400 ME UP TO DATE WITH MATERIAL WE 956 00:42:24,400 --> 00:42:26,640 WERE COVERING SO I WOULDN'T FALL 957 00:42:26,640 --> 00:42:28,480 TOO FAR BEHIND AND IN PHILLY I 958 00:42:28,480 --> 00:42:30,360 HAD SEVERAL POSITIVE EXPERIENCES 959 00:42:30,360 --> 00:42:32,240 ALLOWED TO GO TO EAGLES GAMES 960 00:42:32,240 --> 00:42:34,880 AND MOVIES AND THINGS CONSIDERED 961 00:42:34,880 --> 00:42:38,840 NORMAL. I TOURED THE CITY 962 00:42:38,840 --> 00:42:41,520 SEEING RING TERMINAL 963 00:42:41,520 --> 00:42:44,720 INDEPENDENCE HALL AND LIBERTY 964 00:42:44,720 --> 00:42:52,080 BELL AND ROCKY AND MY ONCE 965 00:42:52,080 --> 00:42:54,280 OPINIONS AND INPUT WERE ALL 966 00:42:54,280 --> 00:42:56,720 VALUED THROUGH THIS PROCESS AND 967 00:42:56,720 --> 00:42:59,080 EFFECTED MY CARE. I HAD SOME 968 00:42:59,080 --> 00:42:59,560 CONTROL. 969 00:42:59,560 --> 00:43:02,320 MY AUTONOMY WAS RESPECTED AND 970 00:43:02,320 --> 00:43:04,080 VOICE WAS HEARD. EVEN WHILE I 971 00:43:04,080 --> 00:43:07,480 WAS JUST A TEENAGER. BY GETTING 972 00:43:07,480 --> 00:43:09,680 CAR OUTPATIENT I WAS ABLE TO 973 00:43:09,680 --> 00:43:11,480 ALMOST MAKE A VACATION OUT OF 974 00:43:11,480 --> 00:43:13,440 EACH TIME I CAME UP HERE. 975 00:43:13,440 --> 00:43:17,720 FRIENDS OF MINE RECEIVED CAR IN 976 00:43:17,720 --> 00:43:19,040 CINCINNATI AFTER THEY GOT A 977 00:43:19,040 --> 00:43:21,400 TRIAL OF THEIR OWN AND SPENT ALL 978 00:43:21,400 --> 00:43:26,680 6 WEEKS OF IN CAR PATIENT WHY? 979 00:43:26,680 --> 00:43:29,000 SAFETY HAS BEEN ESTABLISHED AND 980 00:43:29,000 --> 00:43:31,320 FOR A TREATMENT IN AN OUTPATIENT 981 00:43:31,320 --> 00:43:34,840 SETTING CLINICAL TRIAL OR NOT 982 00:43:34,840 --> 00:43:39,640 WHY KEEP ADOLESCENT IN-PATIENT 983 00:43:39,640 --> 00:43:43,960 SO LONG AND ISOLATE THEM SO LONG 984 00:43:43,960 --> 00:43:47,080 AS NECESSARY. I CAN'T IMAGINE 985 00:43:47,080 --> 00:43:48,360 HOW HORRIBLE MY EXPERIENCE WOULD 986 00:43:48,360 --> 00:43:50,960 HAVE BEEN IF I WAS 650 MILES 987 00:43:50,960 --> 00:43:53,320 AWAY FROM HOME IN IN-PATIENT 988 00:43:53,320 --> 00:43:55,960 EACH OF THE NINE TIMES I 989 00:43:55,960 --> 00:43:58,160 RECEIVED CAR. SOME FAMILIES AND 990 00:43:58,160 --> 00:43:59,920 PATIENTS DON'T HAVE LUXURY 991 00:43:59,920 --> 00:44:01,520 ENJOYING TIME IN THE KRILTY THEY 992 00:44:01,520 --> 00:44:03,080 RECEIVED TREATMENT LIKE I DID. 993 00:44:03,080 --> 00:44:04,520 THEY DON'T HAVE SUPPORT OR 994 00:44:04,520 --> 00:44:09,200 ACCESS TO RESOURCES TO HELP 995 00:44:09,200 --> 00:44:12,840 NEEDED TO MAINTAIN GOOD 996 00:44:12,840 --> 00:44:13,480 PSYCHOSOCIAL INTEGRITY AND CAN'T 997 00:44:13,480 --> 00:44:15,680 BE EXPECTED PATIENTS FAMILIES 998 00:44:15,680 --> 00:44:18,400 SOMEHOW HEAR ABOUT RESOURCE 999 00:44:18,400 --> 00:44:19,960 BUSINESS CHANCE AND UPON 1000 00:44:19,960 --> 00:44:21,880 ENTERING TRIAL ACING CRESS TO 1001 00:44:21,880 --> 00:44:23,080 CERTAIN KNOWLEDGE AND RESOURCES 1002 00:44:23,080 --> 00:44:25,520 BE GIVEN TO THEM TO LOWER 1003 00:44:25,520 --> 00:44:26,960 EMOTIONAL AND MENTAL BURDEN 1004 00:44:26,960 --> 00:44:29,040 COMING WITH NOT ONLY A DIAGNOSIS 1005 00:44:29,040 --> 00:44:30,960 BUT BEING IN A CLINICAL TRIAL 1006 00:44:30,960 --> 00:44:33,040 CANCER ITSELF IS SCARY ENOUGH 1007 00:44:33,040 --> 00:44:34,480 ADD IN A TREATMENT STILL YET TO 1008 00:44:34,480 --> 00:44:36,600 BE USE THE WIDELY IN PRACTICE 1009 00:44:36,600 --> 00:44:38,720 AND IS STILL BEING STUDIED AND 1010 00:44:38,720 --> 00:44:41,040 WHOLE NEW LAYER OF FEAR IS ADDED 1011 00:44:41,040 --> 00:44:43,040 TO THE DISEASE AND TO QUOTE 1012 00:44:43,040 --> 00:44:44,920 ARTICLE RESEARCHING EXPERIENCES 1013 00:44:44,920 --> 00:44:46,360 WITH CHILDREN WITH CANCER 1014 00:44:46,360 --> 00:44:47,480 CONSIDERATIONS FOR PRACTICE AND 1015 00:44:47,480 --> 00:44:49,680 FEAR OF CANCER PAIRED WITH 1016 00:44:49,680 --> 00:44:51,760 ADDITIONAL FEAR OF RECEIVING A 1017 00:44:51,760 --> 00:44:55,520 NEW TREATMENT MAKES CHILDREN 1018 00:44:55,520 --> 00:44:57,920 ADOLESCENCE DOUBLEBLY VULNERABLE 1019 00:44:57,920 --> 00:45:00,960 AND MONSTER UNDER THE BED 1020 00:45:00,960 --> 00:45:03,880 DOESN'T SUDDENLY SEEM IMAGINARY 1021 00:45:03,880 --> 00:45:05,480 ANYMORE NAUSEOUS UNDER THE BED 1022 00:45:05,480 --> 00:45:06,680 FEAR IS TANGIBLE EVERYWHERE IN 1023 00:45:06,680 --> 00:45:08,960 THE ROOM TERRIFYING THE CHILD, 1024 00:45:08,960 --> 00:45:10,920 PARENT AND ENTIRE FAMILY AS THEY 1025 00:45:10,920 --> 00:45:13,600 ENTER TREATMENTS WITH UNKNOWN 1026 00:45:13,600 --> 00:45:13,840 RESULTS. 1027 00:45:13,840 --> 00:45:16,720 AS DOCTORS AND CARETAKERS WE ARE 1028 00:45:16,720 --> 00:45:19,560 THERE TO TELL THEM POTENTIAL 1029 00:45:19,560 --> 00:45:20,280 SIDE-EFFECTS TO EXPECT FROM THE 1030 00:45:20,280 --> 00:45:21,840 TREATMENT AND WHAT THE TREATMENT 1031 00:45:21,840 --> 00:45:23,400 IS SUPPOSED TO ACCOMPLISH. ARE 1032 00:45:23,400 --> 00:45:26,600 WE GIVING THEM RESOURCES TO 1033 00:45:26,600 --> 00:45:28,000 MENTALLY HANDLE TREATMENTS AND 1034 00:45:28,000 --> 00:45:29,600 SIDE-EFFECTS? ARE THEY 1035 00:45:29,600 --> 00:45:33,040 SUPPORTED? CAN THEY HANDLE 1036 00:45:33,040 --> 00:45:34,960 MENTAL BURDEN? DO THEY 1037 00:45:34,960 --> 00:45:37,560 UNDERSTAND WHAT THEY ARE BEING 1038 00:45:37,560 --> 00:45:38,560 TOLD SOMETIMES TOO MUCH 1039 00:45:38,560 --> 00:45:40,800 INFORMATION TO BE PROCESSED AT 1040 00:45:40,800 --> 00:45:42,600 ONCE IF A DECISION DOESN'T HAVE 1041 00:45:42,600 --> 00:45:45,600 TO BE RUSHED DON'T RUSH IT 1042 00:45:45,600 --> 00:45:47,240 EXPLAIN TO PARENT AND PATIENT 1043 00:45:47,240 --> 00:45:50,440 WHAT FUTURE HOLDS AND MAKE SURE 1044 00:45:50,440 --> 00:45:52,800 IT IS UNDERSTOOD NOT EXPECTED 1045 00:45:52,800 --> 00:45:53,840 PARENT COULD EXPLAIN TO CHILD 1046 00:45:53,840 --> 00:45:55,480 WHAT IS GOING ON MY MOM COULD 1047 00:45:55,480 --> 00:45:57,960 BUT THAT IS NOT PARENTS JOB 1048 00:45:57,960 --> 00:45:59,480 BRING RIGHT PEOPLE INTO 1049 00:45:59,480 --> 00:46:00,920 CONVERSATION WHETHER A 1050 00:46:00,920 --> 00:46:04,920 PSYCHIATRIST OR SOCIAL WORKER OR 1051 00:46:04,920 --> 00:46:05,480 CHILD LIKE SPECIALIST OR 1052 00:46:05,480 --> 00:46:06,920 CHAPLAIN BRING THEM IN THE ROOM 1053 00:46:06,920 --> 00:46:09,320 TO MAKE CONVERSATION BETTER AND 1054 00:46:09,320 --> 00:46:10,480 TREATMENT IS UNDERSTOOD AND 1055 00:46:10,480 --> 00:46:12,360 PATIENTS ONCE INPUT IS TAKEN 1056 00:46:12,360 --> 00:46:14,200 INTO ACCOUNT AND SEEMS NEEDED 1057 00:46:14,200 --> 00:46:16,200 HAVE PARENTS STEP OUT SO PATIENT 1058 00:46:16,200 --> 00:46:19,320 COULD GIVE INPUT AND EXPERIENCE 1059 00:46:19,320 --> 00:46:20,640 WITHOUT PARENTAL PRESSURE AND 1060 00:46:20,640 --> 00:46:21,680 PATIENT CONVERSATION WAS 1061 00:46:21,680 --> 00:46:23,440 DIRECTED TO ME AND I WAS 1062 00:46:23,440 --> 00:46:26,600 LISTENED TO ENCOURAGED ME TO 1063 00:46:26,600 --> 00:46:28,800 MOVE FORWARD ATTEMPTING NEW 1064 00:46:28,800 --> 00:46:32,280 TREATMENT AND SAME SHOULD BE 1065 00:46:32,280 --> 00:46:33,840 DONE FOREVERY CHILD. IT IS 1066 00:46:33,840 --> 00:46:37,000 IMPORTANT TO PRIORITIZE THESE 1067 00:46:37,000 --> 00:46:38,320 ALONGSIDE THE TREATMENT ITSELF 1068 00:46:38,320 --> 00:46:40,880 AND NOT JUST EVALUATE SUCCESS OF 1069 00:46:40,880 --> 00:46:42,720 TREATMENT BASED ON HOW EFFECTIVE 1070 00:46:42,720 --> 00:46:44,280 IT IS AGAINST THE DISEASE. 1071 00:46:44,280 --> 00:46:47,960 WHILE I'M AWARE OF LIMITATIONS 1072 00:46:47,960 --> 00:46:50,280 OF HIPAA BEST SUPPORT COMES FROM 1073 00:46:50,280 --> 00:46:51,720 OTHERS EXPERIENCING SAME 1074 00:46:51,720 --> 00:46:53,480 TREATMENT AS PATIENT AND THERE 1075 00:46:53,480 --> 00:46:55,200 IS A WAY TO CONNECT PATIENTS IN 1076 00:46:55,200 --> 00:46:57,240 THE TRIAL WHERE THEY CAN CONSENT 1077 00:46:57,240 --> 00:46:58,880 TO SPEAK TO OTHER FAMILIES GOING 1078 00:46:58,880 --> 00:47:00,920 THROUGH THE TRIAL OR WHO HAVE 1079 00:47:00,920 --> 00:47:02,360 GONE THROUGH IT AND GET 1080 00:47:02,360 --> 00:47:03,680 CONNECTED THROUGH THE HOSPITAL 1081 00:47:03,680 --> 00:47:05,440 AND KNOW THIS PUTS MANY CHILDREN 1082 00:47:05,440 --> 00:47:07,520 AND PARENTS AT EASE AND SPEAKING 1083 00:47:07,520 --> 00:47:09,760 TO THEM RELATING TO EXPERIENCES 1084 00:47:09,760 --> 00:47:12,320 TO AND WHEN EXPERIENCE IS A NEW 1085 00:47:12,320 --> 00:47:13,960 AND FRIGHTENING ONE AT THAT. 1086 00:47:13,960 --> 00:47:15,800 THAT IS ONE OF THE BEST THINGS 1087 00:47:15,800 --> 00:47:18,560 FOR CHILD AND FAMILY WHO HAS 1088 00:47:18,560 --> 00:47:19,920 CANCER TO NOT FEEL ISOLATED AND 1089 00:47:19,920 --> 00:47:22,200 TO BE ABLE TO ELATE TO SOMEONE 1090 00:47:22,200 --> 00:47:24,040 ELSE IN SIMILAR SHOES BECAUSE 1091 00:47:24,040 --> 00:47:26,320 ONLY PEOPLE WHO UNDERSTAND THE 1092 00:47:26,320 --> 00:47:31,160 PATH ARE PEOPLE WHO HAVE WALKED 1093 00:47:31,440 --> 00:47:31,560 IT. 1094 00:47:31,560 --> 00:47:33,680 I MIGHT BE YOUNG AND NAÏVE 1095 00:47:33,680 --> 00:47:35,600 COMING TO OTHER SIDE. I HAVE 1096 00:47:35,600 --> 00:47:38,040 ONLY BEEN A NURSE TWO MONTHS BUT 1097 00:47:38,040 --> 00:47:39,440 THESE ARE MY PERSPECTIVES AND 1098 00:47:39,440 --> 00:47:42,800 WHAT TO FOCUS ON TO IMPROVE 1099 00:47:42,800 --> 00:47:44,480 CLINICAL TRIALS AND BEGINNING TO 1100 00:47:44,480 --> 00:47:47,960 WRAP THIS UP FOLLOWING FAMILY 1101 00:47:47,960 --> 00:47:48,600 PERSPECTIVE COMES FROM MY 1102 00:47:48,600 --> 00:47:50,760 BROTHER ALEX. I INCLUDED IT 1103 00:47:50,760 --> 00:47:52,800 BECAUSE TREATMENT IN THE PATIENT 1104 00:47:52,800 --> 00:47:54,640 EFFECTS THE PATIENTS FAMILY AND 1105 00:47:54,640 --> 00:47:56,640 THEIR PERSPECTIVE SHOULDN'T BE 1106 00:47:56,640 --> 00:47:59,240 LEFT OUT. ALEX GOES ON TO SAY I 1107 00:47:59,240 --> 00:48:01,200 THINK ABOUT PATRICK AND HAVING 1108 00:48:01,200 --> 00:48:04,040 NO ONE REMOTELY CLOSE TO HIM TO 1109 00:48:04,040 --> 00:48:05,680 KEEP HIM COMPANY AND FROM GOING 1110 00:48:05,680 --> 00:48:08,080 STIR CRAZY. TRAPPED IN A 1111 00:48:08,080 --> 00:48:09,800 HOSPITAL ROOM IN AN UNFAMILIAR 1112 00:48:09,800 --> 00:48:11,920 CITY AT ANL WHERE ANGER SURELY 1113 00:48:11,920 --> 00:48:14,720 WAS AT FOREFRONT OF HIS EMOTIONS 1114 00:48:14,720 --> 00:48:16,840 WHILE HE COULDN'T LIVE A NORMAL 1115 00:48:16,840 --> 00:48:18,320 LIFE BUT AT LEAST WHY HE 1116 00:48:18,320 --> 00:48:20,480 COULDN'T BE CLOSER TO HOME WHERE 1117 00:48:20,480 --> 00:48:22,600 HE COULD WELCOME VISITORS, 1118 00:48:22,600 --> 00:48:25,040 FRIENDS, FAMILY, ET CETERA. I 1119 00:48:25,040 --> 00:48:26,800 THINK ABOUT MOM, FINDING NEW 1120 00:48:26,800 --> 00:48:29,800 PATHS AND AREAS TO WALK AND 1121 00:48:29,800 --> 00:48:31,680 WITHOUT ANYONE ABLE TO GO ON 1122 00:48:31,680 --> 00:48:35,160 WITH HER AND BE THAT SHOULDER TO 1123 00:48:35,160 --> 00:48:37,800 LEAN ON AND WHAT PARENT NEEDS TO 1124 00:48:37,800 --> 00:48:40,560 LISTEN TO, TO GET HER THROUGH 1125 00:48:40,560 --> 00:48:43,200 TOUGH TIME AND MUCH LESS TAKING 1126 00:48:43,200 --> 00:48:49,040 CARE OF YOUNGEST SON IN 1127 00:48:49,040 --> 00:48:51,320 UNFAMILIAR TERRITORY AND 1128 00:48:51,320 --> 00:48:53,200 UNFAMILIAR MEDICINE. BY SAME 1129 00:48:53,200 --> 00:48:55,000 TOKEN THAT IS THE LIFE I HAVE 1130 00:48:55,000 --> 00:48:57,600 KNOWN FORGREAT MAJORITY OF MY 1131 00:48:57,600 --> 00:49:00,000 CHILDHOOD AND ADOLESCENCE. IT 1132 00:49:00,000 --> 00:49:02,000 WAS NOT EASY BUT WAS NORM AND 1133 00:49:02,000 --> 00:49:05,440 WHAT MADE IT WORTH IT IS BLIND 1134 00:49:05,440 --> 00:49:07,040 FANL AND HOPE THIS NEW CUTTING 1135 00:49:07,040 --> 00:49:11,840 TREATMENT WOULD BE KEY TO ALLOW 1136 00:49:11,840 --> 00:49:13,280 PATRICK NORMALCY LIVING OUT 1137 00:49:13,280 --> 00:49:15,040 INCREDIBLE STORY. LOOK AT HIM 1138 00:49:15,040 --> 00:49:16,960 LEAVING THE CITY AGAIN TO 1139 00:49:16,960 --> 00:49:18,800 EDUCATE AND INFORM AND INSPIRE 1140 00:49:18,800 --> 00:49:21,680 SO MANY OTHERS THAT WHEN IN DARK 1141 00:49:21,680 --> 00:49:24,840 AND STORMY SUNSHINE IS CLOSER 1142 00:49:24,840 --> 00:49:26,760 THAN ONE MAY THINK. 1143 00:49:26,760 --> 00:49:30,320 FOR ALL FUTURE PATIENTS, I HOPE 1144 00:49:30,320 --> 00:49:32,080 THAT SUNSHINE IS INCREDIBLY 1145 00:49:32,080 --> 00:49:33,720 CLOSE. AS CAREGIVERS, WE ARE 1146 00:49:33,720 --> 00:49:35,600 THE ONES WHO CAN BRING THAT 1147 00:49:35,600 --> 00:49:37,800 SUNSHINE TO THEM. WE HAVE TO 1148 00:49:37,800 --> 00:49:41,400 THINK LIKE A KID IN ORDER TO 1149 00:49:41,400 --> 00:49:43,840 TREAT A KID. 1150 00:49:43,840 --> 00:49:46,480 INNOVATION AND KNOWING VALUE OF 1151 00:49:46,480 --> 00:49:48,280 GREAT CARE AND WHY SWITCH FROM 1152 00:49:48,280 --> 00:49:49,520 ENGINEERING TO NURSING STARTING 1153 00:49:49,520 --> 00:49:54,320 IN 12 DAYS I WILL WORK AT 1154 00:49:54,320 --> 00:49:56,680 CINCINNATI CHILDREN'S ON BONE 1155 00:49:56,680 --> 00:49:59,160 MARROW TRANSPLANT AND EVERYONE 1156 00:49:59,160 --> 00:50:01,000 TREATED ME HAS BEEN THAT 1157 00:50:01,000 --> 00:50:01,920 SUNSHINE FOR ME AND I KNOW 1158 00:50:01,920 --> 00:50:03,760 EVERYONE IF IN THE ROOM HAS BEEN 1159 00:50:03,760 --> 00:50:07,400 THAT SUNSHINE FOR SOME PATIENT 1160 00:50:07,400 --> 00:50:10,040 AT SOME POINT. 1161 00:50:10,040 --> 00:50:11,920 IT IS IMPORTANT TO REALIZE THERE 1162 00:50:11,920 --> 00:50:14,760 IS ALWAYS ROOM IMPROVEMENT. 1163 00:50:14,760 --> 00:50:16,440 NEXT DAY CAN ALWAYS BE BETTER 1164 00:50:16,440 --> 00:50:18,280 AND MORE WE CAN IMPROVE THE 1165 00:50:18,280 --> 00:50:20,720 FUTURE OF CLINICAL TRIALS THE 1166 00:50:20,720 --> 00:50:27,320 BRIGHTER THE FUTURE WILL BE. 1167 00:50:27,320 --> 00:50:30,000 THANK YOU FOR ALLOWING ME TO 1168 00:50:30,000 --> 00:50:40,400 GIVE MY PERSPECTIVE. 1169 00:50:59,200 --> 00:51:01,880 >> WE ARE HERE FOR PATRICK AND 1170 00:51:01,880 --> 00:51:04,240 EVERY PATIENT WHO FOLLOWED AFTER 1171 00:51:04,240 --> 00:51:05,800 HIM I CAN'T BEGIN TO THANK YOU 1172 00:51:05,800 --> 00:51:09,360 FOR STARTING THE CONFERENCE OFF 1173 00:51:09,360 --> 00:51:11,360 THIS WAY. 1174 00:51:11,360 --> 00:51:13,800 WITH THAT WE WILL TRANSITION TO 1175 00:51:13,800 --> 00:51:15,960 SESSION 1 AND YOU ARE OUR FIRST 1176 00:51:15,960 --> 00:51:17,960 SPEAKER AND IF PANELISTS AND 1177 00:51:17,960 --> 00:51:19,640 CHAIRS COULD COME UP TO THE 1178 00:51:19,640 --> 00:51:30,200 STAGE, THAT WOULD BE WONDERFUL. 1179 00:51:34,280 --> 00:51:37,040 >> FIRST OF ALL, IF WE ARE 1180 00:51:37,040 --> 00:51:38,880 COMING TO BE INSPIRED GOALS HAVE 1181 00:51:38,880 --> 00:51:42,520 BEEN ACHIEVED AND WE CAN GO HOME 1182 00:51:42,520 --> 00:51:44,080 NOW. THANKS FOR THOSE POWERFUL 1183 00:51:44,080 --> 00:51:46,400 WORDS. AS WE TRANSITION, I WANT 1184 00:51:46,400 --> 00:51:50,320 TO TAKE A MOMENT TO RECOGNIZE 1185 00:51:50,320 --> 00:51:52,240 NIRALI FOR HER HER KUL AN AN 1186 00:51:52,240 --> 00:51:55,440 EFFORTS IF IN ENGINEERING THIS 1187 00:51:55,440 --> 00:51:56,640 BRILLIANT CONFERENCE AND 1188 00:51:56,640 --> 00:51:58,120 EVERYBODY APPRECIATES HOW SHE 1189 00:51:58,120 --> 00:52:00,320 APPROACHED EVERY DETAIL WITH 1190 00:52:00,320 --> 00:52:01,640 UTMOST THOUGHT AND PRECISION AND 1191 00:52:01,640 --> 00:52:04,040 THINK CONFERENCES LIKE THIS ARE 1192 00:52:04,040 --> 00:52:07,080 USUALLY ORGANIZED BY ABOUT A 1193 00:52:07,080 --> 00:52:11,840 TEAM OF 50. 1194 00:52:11,840 --> 00:52:13,600 THIS WAS ORGANIZED BY A TEAM OF 1195 00:52:13,600 --> 00:52:16,160 1 AND I LOOK AROUND AND 1196 00:52:16,160 --> 00:52:18,480 CONGRATULATE YOU ON BRINGING 1197 00:52:18,480 --> 00:52:21,280 THIS COMMUNITY TOGETHER IN 1198 00:52:21,280 --> 00:52:21,640 PERSON. 1199 00:52:21,640 --> 00:52:29,640 >> [APPLAUSE]. 1200 00:52:29,640 --> 00:52:31,440 >> I'MLY ORA. 1201 00:52:31,440 --> 00:52:34,880 WE KNOW ACROSS CLINICAL TRIALS 1202 00:52:34,880 --> 00:52:36,680 AND COMMERCIAL EXPERIENCE EVENT 1203 00:52:36,680 --> 00:52:38,960 FREE SURVIVAL HAS REALLY EMERGED 1204 00:52:38,960 --> 00:52:41,480 TO BE RELIABLY ABOUT 50%. 1205 00:52:41,480 --> 00:52:44,360 WE HAVE SEEN FROM 3 AND 5 YEAR 1206 00:52:44,360 --> 00:52:46,920 FOLLOW UP DATA AND THAT STEVE 1207 00:52:46,920 --> 00:52:50,480 PRESENTED THAT CURVES REALLY 1208 00:52:50,480 --> 00:52:52,160 PLATEAU. 1209 00:52:52,160 --> 00:52:53,400 THIS LEAVES STILL A SURVIVAL GAP 1210 00:52:53,400 --> 00:52:55,840 THAT NEEDS TO BE CLOSED. MOVING 1211 00:52:55,840 --> 00:52:57,720 TOWARDS ENGINEERING TOWARDS NEXT 1212 00:52:57,720 --> 00:53:00,040 GENERATION CARS WE WILL HEAR 1213 00:53:00,040 --> 00:53:02,320 OVER THE DAY ABOUT PATH 1214 00:53:02,320 --> 00:53:04,600 INCLUDING IDENTIFYING NOVEL 1215 00:53:04,600 --> 00:53:07,000 TARGETS GENERATING CARS WITH 1216 00:53:07,000 --> 00:53:08,520 MULTISPECIFICITY AND ENGINEERING 1217 00:53:08,520 --> 00:53:10,880 CARS TO BE OPTIMIZED FOR 1218 00:53:10,880 --> 00:53:12,600 PERSISTENCE. THEY ARE CRITICAL 1219 00:53:12,600 --> 00:53:14,280 PATHS AND ARE ECONOMICALLY 1220 00:53:14,280 --> 00:53:16,480 TAXING AND REQUIRE TIME AND 1221 00:53:16,480 --> 00:53:17,960 RESOURCE HEAVY FOR DEVELOPMENT 1222 00:53:17,960 --> 00:53:19,800 AND SCALABILITY. WHAT IF WE 1223 00:53:19,800 --> 00:53:22,880 COULD COLLECT OR USE EXISTENT 1224 00:53:22,880 --> 00:53:27,280 DATA TO OPTIMIZE AVAILABLE CAR 1225 00:53:27,280 --> 00:53:29,080 PRODUCTS INCREMENTALLY IMPROVING 1226 00:53:29,080 --> 00:53:31,280 CLINICAL OUTCOME AND CHALLENGE 1227 00:53:31,280 --> 00:53:33,640 IS SINCE COMMERCIALIZATION AND 1228 00:53:33,640 --> 00:53:34,360 SIGNIFICANT PATIENT EXPERIENCE 1229 00:53:34,360 --> 00:53:37,520 HAS AMASSED AND DATA HASN'T 1230 00:53:37,520 --> 00:53:38,880 SYSTEMATICALLY BEEN COLLECTED OR 1231 00:53:38,880 --> 00:53:41,520 EFFECTIVELY MINED AND LED TO 1232 00:53:41,520 --> 00:53:43,000 EMERGENCE OF MULTIPLE 1233 00:53:43,000 --> 00:53:44,200 COLLABORATIVE EFFORTS WITH GOAL 1234 00:53:44,200 --> 00:53:46,920 TO LEVERAGE UNTAPPED CLINICAL 1235 00:53:46,920 --> 00:53:48,600 DATA WE WILL HEAR FROM LOTS OF 1236 00:53:48,600 --> 00:53:50,520 GROUPS DURING THE DAY AND PART 1237 00:53:50,520 --> 00:53:52,000 OF IMPACT HAS BEEN IDENTIFYING 1238 00:53:52,000 --> 00:53:55,760 CLINICAL VARIABLES THAT IMPACT 1239 00:53:55,760 --> 00:53:56,880 OUTCOMES THAT HAVE BEEN BROUGHT 1240 00:53:56,880 --> 00:53:58,760 BACK TO THE PATIENT. I WILL 1241 00:53:58,760 --> 00:54:01,560 DISCUSS SOME OVER IN THE NEXT 1242 00:54:01,560 --> 00:54:03,880 COUPLE OF MINUTES. 1243 00:54:03,880 --> 00:54:05,520 PEDIATRIC REAL WORLD CAR 1244 00:54:05,520 --> 00:54:07,480 CONSORTIUM IS A FORUM FOR DATA 1245 00:54:07,480 --> 00:54:10,680 AND SAMPLE SHARING ACROSS 1246 00:54:10,680 --> 00:54:11,040 INSTITUTIONS. 1247 00:54:11,040 --> 00:54:13,880 WE HAVE A MULTIINSTITUTIONAL 1248 00:54:13,880 --> 00:54:16,080 RETROSPECTIVE STUDY IDENTIFYING 1249 00:54:16,080 --> 00:54:18,880 CO-VARIATES OF OUTCOMES ACROSS 1250 00:54:18,880 --> 00:54:21,520 COHORT OF 185 PATIENTS AND 1251 00:54:21,520 --> 00:54:23,800 MULTIVARIED ANALYSIS IDENTIFIED 1252 00:54:23,800 --> 00:54:26,000 DISEASE BURDEN TO EMERGE AND 1253 00:54:26,000 --> 00:54:27,160 ASSOCIATE WITH DECREASED 1254 00:54:27,160 --> 00:54:29,240 SURVIVAL THAT YOU CAN SEE FROM 1255 00:54:29,240 --> 00:54:32,320 KAPLAN MEYERS HOW DIVERGIENT 1256 00:54:32,320 --> 00:54:34,040 OUTCOMES ARE WITH ONE YEAR 1257 00:54:34,040 --> 00:54:37,040 EVENTS PRESURVIVAL OF ONLY 34% 1258 00:54:37,040 --> 00:54:38,440 OF HIGH DISEASE BURDEN GROUP 1259 00:54:38,440 --> 00:54:43,640 OPPOSED TO 70 P RS IN REMAINING 1260 00:54:43,640 --> 00:54:43,920 PATIENTS. 1261 00:54:43,920 --> 00:54:47,240 IN PARALLEL CAR MA STUDY 1262 00:54:47,240 --> 00:54:50,000 IDENTIFIED THAT BURDEN -- ACROSS 1263 00:54:50,000 --> 00:54:53,600 COHORT OF 420 PATIENTS AND THIS 1264 00:54:53,600 --> 00:54:58,680 DATA WAS CORROBORATED BY 1265 00:54:58,680 --> 00:55:01,560 MULTI-SITE REPORTING BY ST. 1266 00:55:01,560 --> 00:55:05,360 JUDES AND HOPKINS AND BURDEN IS 1267 00:55:05,360 --> 00:55:07,640 CERTIFIGATE OF POOR BIOLOGY AND 1268 00:55:07,640 --> 00:55:10,000 PRIOR TO CAR INFUSION MIGHT 1269 00:55:10,000 --> 00:55:11,400 IMPROVE OUTCOMES AND FURTHER 1270 00:55:11,400 --> 00:55:14,080 STUDY IS WARRANTED AND WANT TO 1271 00:55:14,080 --> 00:55:16,480 HIGHLIGHT REAL-WORLD COHORT WAS 1272 00:55:16,480 --> 00:55:21,040 SKEWED TOWARDS LOWER DISEASE 1273 00:55:21,040 --> 00:55:24,760 BURDEN AND LYMPHOMA BLAST COUNT 1274 00:55:24,760 --> 00:55:29,760 WAS 74% -- 55% OF THE REAL WORLD 1275 00:55:29,760 --> 00:55:31,800 COHORT HAD A BLAST COUNT OF LESS 1276 00:55:31,800 --> 00:55:32,920 THAN 5%. 1277 00:55:32,920 --> 00:55:36,960 WITH EMERGING DATA THAT DISEASE 1278 00:55:36,960 --> 00:55:37,960 BURDEN MATTERS CONSIDERING 1279 00:55:37,960 --> 00:55:40,680 SKEWING TOWARDS LOWER DISEASE 1280 00:55:40,680 --> 00:55:42,280 BURDENED COHORT AND EXPECT 1281 00:55:42,280 --> 00:55:44,400 MATCHED FOR BURDEN THAT OVERALL 1282 00:55:44,400 --> 00:55:46,880 REAL WORLD OUTCOMES WOULD BE 1283 00:55:46,880 --> 00:55:49,760 IMPROVED COMPARED TO ELLI ANA 1284 00:55:49,760 --> 00:55:52,360 AND NUANCED DIFFERENCES TO 1285 00:55:52,360 --> 00:55:53,480 OUTCOMES COMPARED TO PREVIOUS 1286 00:55:53,480 --> 00:55:55,680 CLINICAL TRIALS AND WE LOOKED AT 1287 00:55:55,680 --> 00:55:57,400 VARIABLES IMPACTING OUTCOMES 1288 00:55:57,400 --> 00:56:00,640 THAT I WILL HIGHLIGHT A FEW 1289 00:56:00,640 --> 00:56:03,040 EFFORTS AND LOOKED AT CAR DOSE 1290 00:56:03,040 --> 00:56:05,160 IMPACT AND LED BY 1291 00:56:05,160 --> 00:56:08,240 [INDISCERNIBLE] AND DIVIDING OUR 1292 00:56:08,240 --> 00:56:09,520 DOSES INTO QUARTILES WE SAW 1293 00:56:09,520 --> 00:56:11,280 THERE WAS NO EFFECT FROM DOSE ON 1294 00:56:11,280 --> 00:56:13,200 RESPONSE OR TOXICITY AND WHEN 1295 00:56:13,200 --> 00:56:15,920 LOOKING AT SURVIVAL, PATIENTS 1296 00:56:15,920 --> 00:56:19,080 WITH HIGHEST DISEASE DOSE COHORT 1297 00:56:19,080 --> 00:56:22,040 OR HIGHEST DOSE COHORT HAD 1298 00:56:22,040 --> 00:56:23,640 IMPROVED OVERALL AND EVENT FREE 1299 00:56:23,640 --> 00:56:26,120 SURVIVAL THAT IS CLINICALLY 1300 00:56:26,120 --> 00:56:29,040 MEANINGFUL AND NAVARTIS DOSE 1301 00:56:29,040 --> 00:56:32,920 RANGE IS BROAD WITH MULTIPLE 1302 00:56:32,920 --> 00:56:35,800 DOSES FALLING IN IMPROVED DOSE 1303 00:56:35,800 --> 00:56:38,440 RANGE AND FARMICO KINETICS 1304 00:56:38,440 --> 00:56:41,560 EFFORT LED BY VANESSA AND KEVIN 1305 00:56:41,560 --> 00:56:44,440 AND IDENTIFIED USING CALCULATED 1306 00:56:44,440 --> 00:56:47,560 PK MODEL INFLECTION POINT WITH 1307 00:56:47,560 --> 00:56:50,080 AFC13.8 BELOW WHICH RELAPSE 1308 00:56:50,080 --> 00:56:51,600 LEVEL WAS HIGHER AND WILL HEAR 1309 00:56:51,600 --> 00:56:53,680 MORE ABOUT THIS OVER THE DAY AND 1310 00:56:53,680 --> 00:56:57,000 WILL HEAR FROM FRIZZO IN 1311 00:56:57,000 --> 00:56:59,080 PARALLEL AND EFFORT DONE USING 1312 00:56:59,080 --> 00:57:02,080 MEASURED PK THROUGH ANALYSIS AND 1313 00:57:02,080 --> 00:57:05,280 THEY IDENTIFIED FLU DER AVEEN AC 1314 00:57:05,280 --> 00:57:07,800 LEVEL OF 14 AND WANT TO 1315 00:57:07,800 --> 00:57:09,720 HIGHLIGHT THIS SET 1316 00:57:09,720 --> 00:57:11,520 GEOGRAPHICALLY AND MEK 1317 00:57:11,520 --> 00:57:13,000 ANNISTICALLY THEY WERE DISTINCT 1318 00:57:13,000 --> 00:57:15,120 EFFORTS AND SERVED ACROSS 1319 00:57:15,120 --> 00:57:16,760 VALIDATING EACH OTHER AND 1320 00:57:16,760 --> 00:57:19,440 CLINICAL RELEVANCE HERE IS 1321 00:57:19,440 --> 00:57:21,400 OPTIMIZING THROUGH DER AVEEN 1322 00:57:21,400 --> 00:57:23,840 DOSING AND IT IS AN EASILY 1323 00:57:23,840 --> 00:57:25,000 MODIFIABLE VARIABLE AND IN 1324 00:57:25,000 --> 00:57:27,240 ADDITION TO LOOKING AT CLINICAL 1325 00:57:27,240 --> 00:57:30,280 VARIABLES, NOT IMPACTED OR SORRY 1326 00:57:30,280 --> 00:57:32,840 YES. IMPACT OUTCOMES IT IS 1327 00:57:32,840 --> 00:57:34,280 RECALLY IMPORTANT TO LOOK AT 1328 00:57:34,280 --> 00:57:36,240 VARIABLES NOT IMPACTING OUTCOMES 1329 00:57:36,240 --> 00:57:38,720 AND MULTIINSTITUTIONAL EFFORTS 1330 00:57:38,720 --> 00:57:41,520 PERMIT STUDY OF RARE PATIENT 1331 00:57:41,520 --> 00:57:42,920 SUBSETS SINGLE INSTITUTIONS ARE 1332 00:57:42,920 --> 00:57:45,000 NOT POWERED TO ACHIEVE 1333 00:57:45,000 --> 00:57:47,000 SUFFICIENT SAMPLE SIZES. I WILL 1334 00:57:47,000 --> 00:57:50,120 GO OVER SOME EFFORTS. 1335 00:57:50,120 --> 00:57:51,120 GENERAL [INDISCERNIBLE] LED A 1336 00:57:51,120 --> 00:57:53,160 STUDY LOOKING AT OUTCOMES OF 1337 00:57:53,160 --> 00:57:55,240 PATIENTS TREATED WITH OUT OF 1338 00:57:55,240 --> 00:57:56,800 SPECIFICATION PRODUCTS AND 1339 00:57:56,800 --> 00:57:59,160 IDENTIFIED THAT OUTCOMES AND 1340 00:57:59,160 --> 00:58:01,160 SURVIVAL WERE NOT DIFFERENT. IF 1341 00:58:01,160 --> 00:58:04,040 IN THE SORT OF MOST PROMINENT 1342 00:58:04,040 --> 00:58:05,360 REASON FOR NOT MEETING 1343 00:58:05,360 --> 00:58:09,040 SPECIFICATION DECREASED BY DID 1344 00:58:09,040 --> 00:58:10,240 VIABILITY SUGGESTING THAT 1345 00:58:10,240 --> 00:58:12,880 VIABILITY THRESHOLDS MIGHT HAVE 1346 00:58:12,880 --> 00:58:14,600 BEEN TOO STRINGENT AND RACE 1347 00:58:14,600 --> 00:58:16,880 OUTCOMES AND HISPANIC POPULATION 1348 00:58:16,880 --> 00:58:19,600 AND POPULATION WE KNOW PATIENTS 1349 00:58:19,600 --> 00:58:21,640 ARE HISTORICALLY RESISTANT TO 1350 00:58:21,640 --> 00:58:23,560 CHEMOTHERAPY AND HAVE INFERIOR 1351 00:58:23,560 --> 00:58:25,880 OUTCOMES WITH UP FRONT ALL AND 1352 00:58:25,880 --> 00:58:27,800 GIVEN CAR AND OUTCOMES AND 1353 00:58:27,800 --> 00:58:31,440 CURVES ESSENTIALLY SUPERIMPOSE 1354 00:58:31,440 --> 00:58:33,040 WITH NON-HISPANIC WHITES THAT IS 1355 00:58:33,040 --> 00:58:35,600 A SIGNIFICANT COHORT MAKING UP 1356 00:58:35,600 --> 00:58:37,840 38% OF COHORT. 1357 00:58:37,840 --> 00:58:44,480 WE WILL HEAR FROM ALLIE LEAHY 1358 00:58:44,480 --> 00:58:46,000 ABOUT CYTOGENETICS AND IS 1359 00:58:46,000 --> 00:58:47,600 IMPORTANT WE ARE LEARNING THAT 1360 00:58:47,600 --> 00:58:51,120 RISK STRATIFICATION SYSTEMS WE 1361 00:58:51,120 --> 00:58:52,320 USE FORCHEMOTHERAPY DON'T 1362 00:58:52,320 --> 00:58:53,560 NECESSARILY APPLY TO CAR. WE 1363 00:58:53,560 --> 00:58:57,160 WILL PROBABLY HAVE TO LEARN A 1364 00:58:57,160 --> 00:59:01,040 NEW RISK STRATIFICATION PATTERNS 1365 00:59:01,040 --> 00:59:04,680 FOR CAR T-CELL PATIENTS AND WILL 1366 00:59:04,680 --> 00:59:07,240 HEAR LATER FROM SARAH ABOUT 1367 00:59:07,240 --> 00:59:09,160 [INDISCERNIBLE] AND I LIKE THIS. 1368 00:59:09,160 --> 00:59:11,320 INTERNATIONAL STUDY LOOKED AT 1369 00:59:11,320 --> 00:59:13,040 PATIENTS LESS THAN THREE YEARS 1370 00:59:13,040 --> 00:59:15,800 OF AGE THAT WAS A COHORT 1371 00:59:15,800 --> 00:59:18,440 EXCLUDED FROM ELLI ANA AND THEY 1372 00:59:18,440 --> 00:59:19,800 IDENTIFIED GOOD SURVIVAL THAT 1373 00:59:19,800 --> 00:59:22,920 WAS PRETTY EQUIVALENT TO 1374 00:59:22,920 --> 00:59:32,080 PATIENTS MEETING FDA INDICATION. 1375 00:59:32,080 --> 00:59:33,360 THEY IDENTIFIED COMPARABLE 1376 00:59:33,360 --> 00:59:36,000 SURVIVAL AND IN INFANT PATIENTS 1377 00:59:36,000 --> 00:59:38,360 AND SERVES TO SHOW AND HIGHLIGHT 1378 00:59:38,360 --> 00:59:40,000 BENEFITS OF CROSS-VALIDATION 1379 00:59:40,000 --> 00:59:43,440 ACROSS EFFORTS AND VANESSA LED 1380 00:59:43,440 --> 00:59:45,040 EFFORT LOOKING AT EXTRA 1381 00:59:45,040 --> 00:59:46,760 MEDULLARY DISEASE IDENTIFYING 1382 00:59:46,760 --> 00:59:49,960 PATIENTS WITH CNS AND NON-CNS 1383 00:59:49,960 --> 00:59:51,840 MENTAL DISEASE HAD SURVIVAL 1384 00:59:51,840 --> 00:59:53,200 OUTCOMES OVERLAPPING WITH 1385 00:59:53,200 --> 00:59:54,840 PATIENTS WITHOUT EXTRA MEDULLARY 1386 00:59:54,840 --> 00:59:57,000 DISEASE AND SIGNAL THAT 1387 00:59:57,000 --> 00:59:59,640 PAISHIENTS WITH NON-CNS EXTRA 1388 00:59:59,640 --> 01:00:02,160 MEDULLARY DISEASE MIGHT HAVE 1389 01:00:02,160 --> 01:00:04,640 DECREASED SURVIVAL AND 1390 01:00:04,640 --> 01:00:06,800 INTERNATIONAL GROUPS LOOKS AT 1391 01:00:06,800 --> 01:00:09,640 PATIENTS WITH CNS DISEASE AND 1392 01:00:09,640 --> 01:00:11,520 IDENTIFIED PATIENTS WITH 1393 01:00:11,520 --> 01:00:15,680 ISOLATED CNS RELAPSE HAVE 1394 01:00:15,680 --> 01:00:18,640 INCREASED RISK OF POST CNS 1395 01:00:18,640 --> 01:00:20,720 RELAPSE AND POPULATIONS 1396 01:00:20,720 --> 01:00:21,880 IDENTIFYING DIFFERENT INSIGHTS 1397 01:00:21,880 --> 01:00:23,600 LOOKING AT PATIENTS USING 1398 01:00:23,600 --> 01:00:25,520 DIFFERENT COHORT AND THROUGH A 1399 01:00:25,520 --> 01:00:28,280 DIFFERENT LENS AND WE WILL HEAR 1400 01:00:28,280 --> 01:00:30,400 FROM SARAH AT SESSION 4A ABOUT 1401 01:00:30,400 --> 01:00:32,640 OUTCOMES WITH PATIENTS WITH DOWN 1402 01:00:32,640 --> 01:00:34,680 SYNDROME AND HIGH RISK COHORTS 1403 01:00:34,680 --> 01:00:36,680 OF RISK TOXICITIES AND WILL HEAR 1404 01:00:36,680 --> 01:00:38,240 ABOUT WORK FROM TED AND HOLLY 1405 01:00:38,240 --> 01:00:42,240 AND WANT TO CONCLUDE THAT CAR 1406 01:00:42,240 --> 01:00:45,320 T-CELL OUTCOME ANALYSIS YIELD 1407 01:00:45,320 --> 01:00:47,560 FINDINGS WITH POSSIBLE CLINICAL 1408 01:00:47,560 --> 01:00:48,160 APPLICATIONS LEARNING HIGH 1409 01:00:48,160 --> 01:00:50,480 DISEASE BURDEN ASSOCIATES WITH 1410 01:00:50,480 --> 01:00:51,400 DECREASED SURVIVAL WITH 1411 01:00:51,400 --> 01:00:53,840 OPPORTUNITY TO DEBULK OR IMPROVE 1412 01:00:53,840 --> 01:00:55,880 OUTCOMES AND CONSOLIDATE 1413 01:00:55,880 --> 01:00:57,640 EMISSIONS IN HIGH RISK GROUP AND 1414 01:00:57,640 --> 01:01:01,040 LEARNED INCREASED CAR T-CELL 1415 01:01:01,040 --> 01:01:02,840 DOSE ASSOCIATED WITH SURVIVAL 1416 01:01:02,840 --> 01:01:05,600 AND OPTIMIZE WITH CAR DOSES WHEN 1417 01:01:05,600 --> 01:01:07,760 AVAILABLE AND OPTIMIZED -- AND 1418 01:01:07,760 --> 01:01:13,000 FARMICO KINETICS ASSOCIATES WITH 1419 01:01:13,000 --> 01:01:14,200 DECREASED RELAPSE AND IDENTIFIED 1420 01:01:14,200 --> 01:01:16,600 HIGH RISK POPULATIONS SUCH AS 1421 01:01:16,600 --> 01:01:18,720 PATIENTS WITH HIGH DISEASE 1422 01:01:18,720 --> 01:01:22,240 BURDEN NON-CNS EXTRA MEDULLARY 1423 01:01:22,240 --> 01:01:24,920 WE CAN CONSIDER CONSOLIDATIVE 1424 01:01:24,920 --> 01:01:27,000 THERAPY AND TOXICITY MITIGATION 1425 01:01:27,000 --> 01:01:28,920 STRATEGIES AND WE IDENTIFIED 1426 01:01:28,920 --> 01:01:31,120 CARS VALUED OPTIONS FOR PATIENT 1427 01:01:31,120 --> 01:01:34,160 SUBSETS THAT ARE HISTORICALLY 1428 01:01:34,160 --> 01:01:36,200 CHEMOTHERAPY RESISTANT AND 1429 01:01:36,200 --> 01:01:38,960 INFANTS WITH HISPANIC RACE AND 1430 01:01:38,960 --> 01:01:40,280 PATIENTS WITH DOWN SYNDROME AND 1431 01:01:40,280 --> 01:01:44,240 TAKEAWAY POINT IS ONGOING 1432 01:01:44,240 --> 01:01:45,440 MULTISIGHT COLLABORATIONS ARE 1433 01:01:45,440 --> 01:01:46,920 REQUIRED TO ADDRESS FOR 1434 01:01:46,920 --> 01:01:47,640 OUTSTANDING QUESTIONS IN THE 1435 01:01:47,640 --> 01:01:49,000 FIELD AND WITH THAT I WILL THANK 1436 01:01:49,000 --> 01:01:52,680 YOU AND MOVE TO THE NEXT SPEAK 1437 01:01:57,120 --> 01:01:57,240 ER. 1438 01:01:57,240 --> 01:01:58,000 >> [APPLAUSE]. 1439 01:01:58,000 --> 01:02:00,240 >> THANK YOU. NEXT SPEAKER IS 1440 01:02:00,240 --> 01:02:03,000 REGINA MEYERS WHO WILL DISCUSS 1441 01:02:03,000 --> 01:02:04,680 IMPACT OF PRIOR THERAPY AND CAR 1442 01:02:04,680 --> 01:02:07,760 TIMING AND WILL DO QUESTIONS FOR 1443 01:02:07,760 --> 01:02:11,040 SPEAKERS AT THE END. 1444 01:02:11,040 --> 01:02:15,640 >> GOOD MORNING, EVERYONE. 1445 01:02:15,640 --> 01:02:17,000 TALKING ABOUT PRIOR THERAPY ON 1446 01:02:17,000 --> 01:02:18,600 CAR T-CELL OUTCOMES. 1447 01:02:18,600 --> 01:02:20,840 AS WE KNOW CAR T-CELL THERAPY 1448 01:02:20,840 --> 01:02:23,520 CAN BE GIVEN TO PATIENTS AT 1449 01:02:23,520 --> 01:02:25,400 VARIOUS POINTS AND 1450 01:02:25,400 --> 01:02:26,000 [INDISCERNIBLE] MIGHT HAVE 1451 01:02:26,000 --> 01:02:27,120 DIFFERENT PRIOR THERAPY 1452 01:02:27,120 --> 01:02:28,960 EXPOSURES TO IMPACT CAR OUTCOMES 1453 01:02:28,960 --> 01:02:31,480 AND ARE A FEW SPECIFIC THERAPIES 1454 01:02:31,480 --> 01:02:33,600 THAT HAVE BEEN OF GREAT INTEREST 1455 01:02:33,600 --> 01:02:40,840 AND ANTI-CD19 AND CD3 BITE -- 1456 01:02:40,840 --> 01:02:43,760 FOR THIS REASON PATIENTS WITH 1457 01:02:43,760 --> 01:02:52,280 EXPOSURE WERE SCOMPLUDED FROM 1458 01:02:52,280 --> 01:02:54,240 INITIALLE -- MAKING THIS A 1459 01:02:54,240 --> 01:02:57,800 CRITICAL QUESTION TO ADDRESS AND 1460 01:02:57,800 --> 01:02:59,520 NEXT OF CONSIDER IS -- SEVERAL 1461 01:02:59,520 --> 01:03:01,560 CONCERNS HAVE BEEN RAISED HERE 1462 01:03:01,560 --> 01:03:06,240 ABOUT POTENTIAL EFFECTS OF INO 1463 01:03:06,240 --> 01:03:10,280 T-CELL CORRECTION AND SIMILARLY 1464 01:03:10,280 --> 01:03:12,800 -- USED FREAK WENTLY IN RELAPSE 1465 01:03:12,800 --> 01:03:17,200 SETTING AND TESTED IN THE 1466 01:03:17,200 --> 01:03:19,240 TREATMENT SETTING AND RAISING 1467 01:03:19,240 --> 01:03:21,200 AND MAIN QUESTION HERE AROUND 1468 01:03:21,200 --> 01:03:23,720 PRODUCT MANUFACTURER FROM DONOR 1469 01:03:23,720 --> 01:03:25,000 T-CELLS LEADING TO DIFFERENT 1470 01:03:25,000 --> 01:03:26,680 OUTCOMES AND STARTING WITH 1471 01:03:26,680 --> 01:03:28,000 [INDISCERNIBLE] AND FIRST STUDY 1472 01:03:28,000 --> 01:03:30,160 LOOKING AT ASSOCIATION WITH 1473 01:03:30,160 --> 01:03:32,840 RESPONSE TO CAR 19 WAS 1474 01:03:32,840 --> 01:03:34,920 RETROSPECTIVE STUDY OUT OF CHUCK 1475 01:03:34,920 --> 01:03:38,080 INCLUDING 166 PATIENTS TREATED 1476 01:03:38,080 --> 01:03:41,680 BETWEEN 2012 AND 2016 AND 1477 01:03:41,680 --> 01:03:43,760 EXPOSED PATIENTS WITH R LIKELY 1478 01:03:43,760 --> 01:03:47,800 TO BE CD19 DIM PROFUSION AND IN 1479 01:03:47,800 --> 01:03:49,320 VIDEO YOU SEE HERE THEY WERE 1480 01:03:49,320 --> 01:03:51,640 MORE LIKELY TO HAVE COMPOSITE 1481 01:03:51,640 --> 01:03:54,920 POOR OUTCOME OF NO RESPONSE OR 1482 01:03:54,920 --> 01:03:58,880 CD19 RELAPSE COMPARED TO BLOOD 1483 01:03:58,880 --> 01:04:01,960 OF NAÏVE PATIENTS BUILDING ON 1484 01:04:01,960 --> 01:04:04,640 THIS MULTI-SITE STUDY IN FRANCE 1485 01:04:04,640 --> 01:04:07,000 LOOKING AT RISK FACTORS 1486 01:04:07,000 --> 01:04:09,720 ASSOCIATED WITH OUTCOMES AND 1487 01:04:09,720 --> 01:04:12,080 PATIENTS BETWEEN 2016 AND 2019 1488 01:04:12,080 --> 01:04:17,760 AND 51 PATIENTS IN ANALYSIS AND 1489 01:04:17,760 --> 01:04:26,840 7 TAENWHOM RECEIVED PRIO BLENA. 1490 01:04:26,840 --> 01:04:30,480 BY MULTIVARIABLE MODELING IT 1491 01:04:30,480 --> 01:04:34,640 REMAINED INDEPENDENTLY 1492 01:04:34,640 --> 01:04:35,880 ASSOCIATED. BUILDING ON THIS 1493 01:04:35,880 --> 01:04:39,280 CAR MULTICENTER ANALYSIS WAS 1494 01:04:39,280 --> 01:04:41,360 CONDUCTED COLLABORATIVE EFFORT 1495 01:04:41,360 --> 01:04:44,360 AMONG 7 CENTERS CAME TOGETHER TO 1496 01:04:44,360 --> 01:04:46,720 ADDRESS IMPACT OF EXPOSURE ON 1497 01:04:46,720 --> 01:04:49,800 CD19 CAR OUTCOMES ANALYSIS 1498 01:04:49,800 --> 01:04:53,160 INCLUDED 420 PATIENTS. CENTERS 1499 01:04:53,160 --> 01:04:54,600 REPRESENTED BELOW AND BREAKDOWN 1500 01:04:54,600 --> 01:04:58,680 OF PATIENTS BY SITE AND VARIETY 1501 01:04:58,680 --> 01:05:02,440 OF CAR CONSTRUCTS AND -- CD19 1502 01:05:02,440 --> 01:05:06,040 AND CD28 CONSTRUCT AND 1503 01:05:06,040 --> 01:05:06,840 [INDISCERNIBLE]. 1504 01:05:06,840 --> 01:05:11,960 SO, INITIALLY WE FOUND WHAT WAS 1505 01:05:11,960 --> 01:05:13,440 HYPOTHESIZED IN SMALLER STUDIES 1506 01:05:13,440 --> 01:05:17,520 AND PATIENTS RECEIVING 420 HAD 1507 01:05:17,520 --> 01:05:21,080 WORSE EFS AND BECAME INTERESTING 1508 01:05:21,080 --> 01:05:23,640 BREAKING IT DOWN FURTHER AND 1509 01:05:23,640 --> 01:05:26,720 BROKE PATIENTS DOWN TO RESPONSE 1510 01:05:26,720 --> 01:05:29,600 TO THIS AND WE COMPARE EFS AMONG 1511 01:05:29,600 --> 01:05:32,760 THREE GROUPS YOU SEE IN THE 1512 01:05:32,760 --> 01:05:34,680 FIGURE HERE THAT BLINA 1513 01:05:34,680 --> 01:05:36,640 RESPONDERS AND PATIENTS HAD 1514 01:05:36,640 --> 01:05:40,840 IDENTICAL EFS AND PATIENTS WERE 1515 01:05:40,840 --> 01:05:43,280 REFRACTORY TO BLINA WITH 1516 01:05:43,280 --> 01:05:45,520 [INDISCERNIBLE] NOW, STUDY CAN 1517 01:05:45,520 --> 01:05:47,000 ADDRESS MECHANISM OF ASSOCIATION 1518 01:05:47,000 --> 01:05:49,880 AND HYPOTHESES HERE IS 1519 01:05:49,880 --> 01:05:52,360 NONRESPONSE IS NEARLY SURROGATE 1520 01:05:52,360 --> 01:05:54,200 FROM REFRACTORY DISEASE. WE 1521 01:05:54,200 --> 01:05:58,360 LOOKED AT THIS NEXT AND 1522 01:05:58,360 --> 01:06:04,840 PREINFUSION DISEASE BURDEN IS -- 1523 01:06:04,840 --> 01:06:06,800 HIGH DISEASE BURDEN PATIENTS 1524 01:06:06,800 --> 01:06:08,960 HAVE HIGH MERCURY CFS AND 1525 01:06:08,960 --> 01:06:10,600 COMBINE THAT WITH RESPONSE DATA 1526 01:06:10,600 --> 01:06:13,480 AND IN THE BLINA THIS IS IN 1527 01:06:13,480 --> 01:06:17,520 BLINA EXPOSED PATIENTS FOR EASE 1528 01:06:17,520 --> 01:06:19,960 OF SHOWING YOU ON GRAPH HERE AND 1529 01:06:19,960 --> 01:06:22,320 STEPWISE DECREASE WITH PATIENTS 1530 01:06:22,320 --> 01:06:24,240 WITH LOW DISEASE BURDEN HAVING 1531 01:06:24,240 --> 01:06:27,120 BEST EFS AND THOSE COMING INTO 1532 01:06:27,120 --> 01:06:31,000 CAR AFTER BEING BLINA REFRACTRY 1533 01:06:31,000 --> 01:06:32,920 AND HIGH DISEASE BURDEN THAT IS 1534 01:06:32,920 --> 01:06:36,640 DISMAL WITH EFS AND NO LONG-TERM 1535 01:06:36,640 --> 01:06:38,520 SURVIVORS THERE AND CONCERN OF 1536 01:06:38,520 --> 01:06:40,040 IMPACTS WITH MODULATION WE 1537 01:06:40,040 --> 01:06:44,760 WANTED TO LOOK ALSO AT CD19 DIM 1538 01:06:44,760 --> 01:06:46,280 EXPRESSION PREPAR AND THIS LOOKS 1539 01:06:46,280 --> 01:06:51,520 AT PATIENTS RECEIVING THIS AND 1540 01:06:51,520 --> 01:06:53,360 -- BLINA NAÏVE PATIENTS WERE 1541 01:06:53,360 --> 01:06:55,240 [INDISCERNIBLE] AND VIRTUALLY 1542 01:06:55,240 --> 01:06:58,720 SAME OUTCOMES PATIENTS UNIFORM 1543 01:06:58,720 --> 01:07:04,800 LY [INDISCERNIBLE] BECAME CD19 1544 01:07:04,800 --> 01:07:08,400 DIM FOLLOWING BLINA WITH DISMAL 1545 01:07:08,400 --> 01:07:11,400 OUTCOMES RELAPSING WITH CD19 1546 01:07:11,400 --> 01:07:15,800 NEGATIVE DISEASE AND LOOKING AT 1547 01:07:15,800 --> 01:07:17,360 PATIENTS WITH NORMAL EXPRESSION 1548 01:07:17,360 --> 01:07:20,880 AND RELANCE IMMUNOPHENOTYPE DID 1549 01:07:20,880 --> 01:07:24,080 NOT DIFFER BY BLINA EXPOSURE AND 1550 01:07:24,080 --> 01:07:28,160 RATES WERE SIMILAR SHOWING CD19 1551 01:07:28,160 --> 01:07:31,360 ANTIGEN ESCAPE IS NOT PRIMARY 1552 01:07:31,360 --> 01:07:33,440 DRIVER EXPOSING DIFFERENCE IF IN 1553 01:07:33,440 --> 01:07:35,240 PATIENTS AND TAKING DATA 1554 01:07:35,240 --> 01:07:37,360 TOGETHER WE CAN DRAW A FEW 1555 01:07:37,360 --> 01:07:39,960 CONCLUSIONS ASKING MORE 1556 01:07:39,960 --> 01:07:41,720 QUESTIONS AND PRIOR BLINA 1557 01:07:41,720 --> 01:07:42,400 EXPOSURE DOESN'T PROVE RESPONSE 1558 01:07:42,400 --> 01:07:45,240 TO CAR BUT IS ASSOCIATED WITH 1559 01:07:45,240 --> 01:07:48,040 WORSE OUTCOMES AND SPECIFICALLY 1560 01:07:48,040 --> 01:07:51,440 NONRESPONSE TO PRIOR BLINA AND 1561 01:07:51,440 --> 01:07:51,920 EXPLANATIONS HOO ERR IS 1562 01:07:51,920 --> 01:07:56,440 REFLECTIVE T-CELL -- ADVERSE 1563 01:07:56,440 --> 01:07:58,680 IMPACT OF EXTENSIVE PRIOR 1564 01:07:58,680 --> 01:08:03,040 THERAPY THE RESPONSE IS 1565 01:08:03,040 --> 01:08:06,960 SURROGATE NONREFRACTORY DISEASE 1566 01:08:06,960 --> 01:08:10,680 REFLANCE OF BLINA TIMING IS 1567 01:08:10,680 --> 01:08:19,880 STILL NOT KNOWN. 1568 01:08:19,880 --> 01:08:22,120 OKAY. SO, THE FIRST DATA 1569 01:08:22,120 --> 01:08:24,400 PUBLISHED BY THIS IS RELATIVELY 1570 01:08:24,400 --> 01:08:26,480 SMALL RETROSPECTIVE SERIES 1571 01:08:26,480 --> 01:08:28,800 SHOWING CONSISTENTLY WORSE 1572 01:08:28,800 --> 01:08:33,680 OUTCOMES AND THIS MULTICENTER UK 1573 01:08:33,680 --> 01:08:37,480 SERIES EXPOSED -- THREE RECEIVED 1574 01:08:37,480 --> 01:08:40,000 THIS AND TWO HAD SUCCESSFUL 1575 01:08:40,000 --> 01:08:43,560 MANUFACTURER AND CURVES HERE INO 1576 01:08:43,560 --> 01:08:45,400 EXPOSED PATIENTS HAD WORSE THAN 1577 01:08:45,400 --> 01:08:47,200 OS AND [INDISCERNIBLE] PATIENTS 1578 01:08:47,200 --> 01:08:50,240 AND SAME MULTICENTERED FAMILY 1579 01:08:50,240 --> 01:08:54,160 FROM FRANCE AND STUDY LOOKED AT 1580 01:08:54,160 --> 01:08:55,600 11INO EXPOSED PATIENTS IN 1581 01:08:55,600 --> 01:08:58,440 ANALYSIS AND EFS WAS WORSE THAN 1582 01:08:58,440 --> 01:09:00,320 PATIENTS AND OS WAS WORSE THAN 1583 01:09:00,320 --> 01:09:02,720 THAT AMONG INO EXPOSED AND 1584 01:09:02,720 --> 01:09:04,520 RECENTLY THERE WAS INTERNATIONAL 1585 01:09:04,520 --> 01:09:07,400 10 CORRECTOR RETROSPECTIVE 1586 01:09:07,400 --> 01:09:10,600 ANALYSIS PUBLISHED THAT INCLUDED 1587 01:09:10,600 --> 01:09:13,400 39INO PATIENTS AND 27 IS 1588 01:09:13,400 --> 01:09:15,200 BRIDGING THERAPY AND NOTABLY 1589 01:09:15,200 --> 01:09:16,960 THIS WAS HEAVILY PRETREATED 1590 01:09:16,960 --> 01:09:19,200 SAMPLE AND MAJORITY OF PATIENTS 1591 01:09:19,200 --> 01:09:23,640 HAD LOW DISEASE BURDEN PRECAR 19 1592 01:09:23,640 --> 01:09:25,360 AND SUCCESSFUL MANUFACTURER AND 1593 01:09:25,360 --> 01:09:28,960 FIGURE SHOWS EFS AND ONS AND 12 1594 01:09:28,960 --> 01:09:31,880 MONTH ESTIMATES ARE SIMILAR TO 1595 01:09:31,880 --> 01:09:33,400 GENERAL PUBLISH THE CAR OUTCOME 1596 01:09:33,400 --> 01:09:36,320 DATA AND LOOKING AT PERSISTENCE 1597 01:09:36,320 --> 01:09:40,200 34 OUT OF 39 PATIENTS RECEIVED B 1598 01:09:40,200 --> 01:09:47,440 CELL AMRASHIA AND 1/3 LOSS 1599 01:09:47,440 --> 01:09:50,760 PROPORTION DIDN'T DIFFER BY 1600 01:09:50,760 --> 01:09:54,320 PATIENTS RECEIVING -- FOLLOWING 1601 01:09:54,320 --> 01:09:57,000 RELAPSE OF THOSE WITH 1602 01:09:57,000 --> 01:09:59,000 NONRESPONSE OR RELAPSE WAS HALF 1603 01:09:59,000 --> 01:10:01,240 CD19 POSITIVE AND HALF CD19 1604 01:10:01,240 --> 01:10:02,960 NEGATIVE AND PUTTING DATA 1605 01:10:02,960 --> 01:10:06,920 TOGETHER SIMILARLY DATA BEFORE 1606 01:10:06,920 --> 01:10:08,880 CONCLUSIONS AND QUESTIONS AND 1607 01:10:08,880 --> 01:10:14,440 T-CELLS COLLECTED AND 1608 01:10:14,440 --> 01:10:15,760 SUCCESSFULLY USED TO MANUFACTURE 1609 01:10:15,760 --> 01:10:18,160 CAR AND THERE IS CONFLICTING 1610 01:10:18,160 --> 01:10:21,440 DATA REPORT AND LARGEST ANALYSIS 1611 01:10:21,440 --> 01:10:24,440 SHOWS SIMILAR RATES TO EXPOSE 1612 01:10:24,440 --> 01:10:27,280 THE PATIENTS AND UNKNOWN HOW 1613 01:10:27,280 --> 01:10:30,440 TIMING IMPACTS INO EXPOSURE ON 1614 01:10:30,440 --> 01:10:31,720 OUTCOMES AND CUMULATIVE DOSING 1615 01:10:31,720 --> 01:10:34,240 AND WANT TO NOTE THERE IS 1616 01:10:34,240 --> 01:10:35,320 PRACTICE VARIATION WHEN TO 1617 01:10:35,320 --> 01:10:40,000 INFUSE CAR IN PATIENTS ACHIEVING 1618 01:10:40,000 --> 01:10:42,680 -- FOR INSTANCE IN CENTER WE 1619 01:10:42,680 --> 01:10:47,040 WAIT FOR PATIENTS TO DEMONSTRATE 1620 01:10:47,040 --> 01:10:51,120 RECOVERY AND CAR AND CENTERS GO 1621 01:10:51,120 --> 01:10:51,840 DIRECTLY AND FURTHER 1622 01:10:51,840 --> 01:10:54,800 UNDERSTANDING IMPACT OF INO 1623 01:10:54,800 --> 01:10:56,760 PERSISTENCE AND ENCOURAGING DATA 1624 01:10:56,760 --> 01:10:59,520 ABOUT INO AND IMPACT OF HIGH 1625 01:10:59,520 --> 01:11:00,480 DISEASE AND INTERESTING QUESTION 1626 01:11:00,480 --> 01:11:03,440 COMING UP IS INO A POTENTIALLY 1627 01:11:03,440 --> 01:11:05,680 EFFECTIVE BRIDGING STRATEGY FOR 1628 01:11:05,680 --> 01:11:11,040 REDUCING BURDEN IN PATIENTS WITH 1629 01:11:11,040 --> 01:11:21,480 CHEMOREFRACTORY DISEASE. 1630 01:11:24,040 --> 01:11:25,920 SO, FIRST WAS THEY SHOWED NICELY 1631 01:11:25,920 --> 01:11:27,720 THAT INCREASED NUMBERS OF LINES 1632 01:11:27,720 --> 01:11:30,240 OF PRIOR THERAPY WAS ADVERSELY 1633 01:11:30,240 --> 01:11:37,360 IMPACTED WITH SURVIVAL AFTER CAR 1634 01:11:37,360 --> 01:11:38,880 PRIOR TRANSPLANT WASN'T 1635 01:11:38,880 --> 01:11:40,840 ASSOCIATED WITH OUTCOMES AND 1636 01:11:40,840 --> 01:11:44,440 LOOKS LIKE PROTECTIVE EFFECTIVE 1637 01:11:44,440 --> 01:11:45,400 PRIOR TRANSPLANT. 1638 01:11:45,400 --> 01:11:46,960 I THINK I QUESTION HOW MUCH OF 1639 01:11:46,960 --> 01:11:49,520 THIS IS CONFOUNDED BY DISEASE 1640 01:11:49,520 --> 01:11:51,920 REFRACTORY ENOUGH AND HAVE WE 1641 01:11:51,920 --> 01:11:54,480 NOT QUITE DISENTANGLED THIS 1642 01:11:54,480 --> 01:11:56,720 ENOUGH YET? BRINGING TOGETHER 1643 01:11:56,720 --> 01:12:00,120 IN CONCLUSION I THINK FOR BLINA 1644 01:12:00,120 --> 01:12:02,160 DATA WE HAVE SHOWN AGAIN IT 1645 01:12:02,160 --> 01:12:03,520 DOESN'T HAVE A RESPONSE TO CAR 1646 01:12:03,520 --> 01:12:06,400 BUT IS ASSOCIATED WITH INFERIOR 1647 01:12:06,400 --> 01:12:09,640 CAR OUTCOMES AND PATIENTS WITH 1648 01:12:09,640 --> 01:12:12,400 RESPONSE TO IT AND WE NEED MORE 1649 01:12:12,400 --> 01:12:15,000 WORK TO UNDERSTAND CONFLICTING 1650 01:12:15,000 --> 01:12:17,840 REPORTS AND EXPOSURES ASSOCIATED 1651 01:12:17,840 --> 01:12:21,480 WITH OUTCOMES AND MAYBE IT HAD 1652 01:12:21,480 --> 01:12:23,680 IS NOT YET BEEN DISENTANGLED 1653 01:12:23,680 --> 01:12:25,680 ENOUGH AND IMPACK OF TIMING OF 1654 01:12:25,680 --> 01:12:28,440 THERAPIES RELATION TO CAR HAS TO 1655 01:12:28,440 --> 01:12:31,560 BE BETTER ILLUS DATED ESPECIALLY 1656 01:12:31,560 --> 01:12:34,720 WITH THERAPIES IN OVERALL 1657 01:12:34,720 --> 01:12:37,880 SETTING AND BEST INFORMING 1658 01:12:37,880 --> 01:12:41,280 OPTIMAL CAR TIMING AND BRIDGING 1659 01:12:41,280 --> 01:12:41,600 STRATEGIES. 1660 01:12:41,600 --> 01:12:44,280 WITH THAT, I WOULD LIKE TO BE 1661 01:12:44,280 --> 01:12:45,600 HAPPY TO TAKE QUESTIONS I KNOW 1662 01:12:45,600 --> 01:12:50,120 AT END OF THIS AND HOPING THAT 1663 01:12:50,120 --> 01:12:50,800 DATA CAN SPARK DISCUSSION 1664 01:12:50,800 --> 01:12:55,520 AMONGST THIS GROUP. THANK YOU. 1665 01:12:55,520 --> 01:12:57,880 >> THANK YOU REGINA AND NEXT IS 1666 01:12:57,880 --> 01:13:02,160 MAR CELLA TALKING ABOUT CDIR AND 1667 01:13:02,160 --> 01:13:05,040 CAR SPECIFIC DATA CAPTURE. 1668 01:13:05,040 --> 01:13:06,560 >> THANK YOU VERY MUCH. THANK 1669 01:13:06,560 --> 01:13:08,920 YOU FOR INVITATION TO 1670 01:13:08,920 --> 01:13:10,080 PARTICIPATE HERE AND FOR 1671 01:13:10,080 --> 01:13:18,240 INCLUDING ME. SO, I WILL TALK 1672 01:13:18,240 --> 01:13:22,640 ABOUT RESOURCE AND DISCLOSURES 1673 01:13:22,640 --> 01:13:24,920 RELATED TO THIS AND PATIENT 1674 01:13:24,920 --> 01:13:28,160 OUTCOME REGISTRIES NOW WITH CAR 1675 01:13:28,160 --> 01:13:31,760 T-CELL AND WITH TRYING TO USED 1676 01:13:31,760 --> 01:13:34,920 THIS FOR MULTIPLE GROUPS AND 1677 01:13:34,920 --> 01:13:39,280 UTILIZING THIS FOR DIFFERENT 1678 01:13:39,280 --> 01:13:40,440 SOURCES INCLUDING REGULATORY 1679 01:13:40,440 --> 01:13:42,680 THAT IS NOT FREQUENTLY USED 1680 01:13:42,680 --> 01:13:44,280 BEFORE AND I'M PERSONALLY HAVING 1681 01:13:44,280 --> 01:13:47,000 THE SAME VIEW AS THIS IS NOT OR 1682 01:13:47,000 --> 01:13:48,280 SHOULD NOT BE ANSWER FOR 1683 01:13:48,280 --> 01:13:50,560 EVERYTHING BUT SHOULD BE PART OF 1684 01:13:50,560 --> 01:13:52,840 ECOSYSTEM OF DATA BASES THAT ARE 1685 01:13:52,840 --> 01:13:54,920 AVAILABLE AND SHOULD INTEGRATE 1686 01:13:54,920 --> 01:13:56,840 THIS WITH DIFFERENT DATA BASES 1687 01:13:56,840 --> 01:14:00,280 BEING ALREADY COLLECTED AND WE 1688 01:14:00,280 --> 01:14:02,880 DON'T MAKE THIS REALLY 1689 01:14:02,880 --> 01:14:06,440 REPETITIVE WORK FOR PEOPLE 1690 01:14:06,440 --> 01:14:07,840 PARTICIPATING WITH DATA 1691 01:14:07,840 --> 01:14:09,720 COLLECTION AND REAL WORLD DATA 1692 01:14:09,720 --> 01:14:11,320 IS COOL AND NEW TERM THAT PEOPLE 1693 01:14:11,320 --> 01:14:13,600 USE ALL THE TIME AND WE WANT TO 1694 01:14:13,600 --> 01:14:15,400 REALLY HAVE SORT OF INTEGRATED 1695 01:14:15,400 --> 01:14:18,800 WAY OF USING THIS REAL WORLD 1696 01:14:18,800 --> 01:14:21,320 DATA THAT CAN HAVE CERTAIN 1697 01:14:21,320 --> 01:14:22,800 CRITERIA THAT WE ESTABLISH BY 1698 01:14:22,800 --> 01:14:26,120 FDA AND OTHER GROUPS TO TRY TO 1699 01:14:26,120 --> 01:14:29,280 USE THIS AS REGULATORY. 1700 01:14:29,280 --> 01:14:33,200 GOING TO NEXT STAGE TO 1701 01:14:33,200 --> 01:14:35,120 UNDERSTAND USE OF THIS TO 1702 01:14:35,120 --> 01:14:38,720 MAXIMIZE THIS FOR RESEARCH OR 1703 01:14:38,720 --> 01:14:40,600 REGULATORY USES. 1704 01:14:40,600 --> 01:14:44,960 CAR T-CELL IS NOT SAME REALLY 1705 01:14:44,960 --> 01:14:48,920 PROCESS THAT WE ARE TRYING TO 1706 01:14:48,920 --> 01:14:50,960 APPLY IT AND TIMELINE OF 1707 01:14:50,960 --> 01:14:52,440 DEVELOPMENT ARE ENLTRY AND LOTS 1708 01:14:52,440 --> 01:14:55,960 HELPED DEVELOP AND THIS IS A 1709 01:14:55,960 --> 01:14:58,880 RESOURCE FOR COMMUNITY BUILT BY 1710 01:14:58,880 --> 01:15:00,440 COMMUNITY AND SHOULD BE PART OF 1711 01:15:00,440 --> 01:15:04,200 ALL EFFORTS GOING FORWARD THAT 1712 01:15:04,200 --> 01:15:08,520 SHOWED AN EXPOSURE IN FIELD 1713 01:15:08,520 --> 01:15:10,560 CONTINUING PRESENTATION WE HEARD 1714 01:15:10,560 --> 01:15:14,640 FROM DR. GRUPP EARLIER. WE ARE 1715 01:15:14,640 --> 01:15:17,320 TRYING TO USE DATA AS SINGLE WAY 1716 01:15:17,320 --> 01:15:19,840 OF CAPTURING ALL EXPERIENCE FROM 1717 01:15:19,840 --> 01:15:22,360 PATIENTS FOR REGULATORY PURPOSES 1718 01:15:22,360 --> 01:15:27,240 AND WE HAVE ALL THESE PROJECTS 1719 01:15:27,240 --> 01:15:28,400 CALLED POST AUTHORIZATION 1720 01:15:28,400 --> 01:15:31,520 PROTOCOLS CAPTURING DATA NOT 1721 01:15:31,520 --> 01:15:33,640 HAVING INDUSTRY CREATING 1722 01:15:33,640 --> 01:15:34,560 SEPARATE REGISTRIES TOGETHER AND 1723 01:15:34,560 --> 01:15:36,440 USING STANDARDIZED APPROACH TO 1724 01:15:36,440 --> 01:15:38,280 CLEK ALL THIS AND SUCCESSFULLY 1725 01:15:38,280 --> 01:15:40,480 HAVE BEEN DOING THIS THAT HAVE 1726 01:15:40,480 --> 01:15:42,640 ALL COMMERCIAL PRODUCTS BEING 1727 01:15:42,640 --> 01:15:45,720 COLLECTED AND OF INTEREST FOR 1728 01:15:45,720 --> 01:15:51,080 THIS AUDIENCE WE ARE ONGO GOING 1729 01:15:51,080 --> 01:15:52,960 CAPTURING PEDIATRIC DATA AND 1730 01:15:52,960 --> 01:15:55,160 CLOSE TO PATIENTS ON ACCRUAL AND 1731 01:15:55,160 --> 01:15:56,920 HOW DOES THIS LOOK NOW? 1732 01:15:56,920 --> 01:16:00,000 WE ARE REACHING ALMOST 10,000 1733 01:16:00,000 --> 01:16:03,200 PATIENT MARKING WITH MORE 1734 01:16:03,200 --> 01:16:05,240 INFUSIONS AND LOTS OF DOUBLE 1735 01:16:05,240 --> 01:16:06,960 INFUSIONS ARE IN PEDIATRIC A 1736 01:16:06,960 --> 01:16:09,720 WILL. L AND DISTRIBUTION 80% IS 1737 01:16:09,720 --> 01:16:12,160 COMMERCIAL AND DISTRIBUTION OF 1738 01:16:12,160 --> 01:16:15,760 PRODUCTS WE HAVE AND 30% ARE 1739 01:16:15,760 --> 01:16:16,880 [INDISCERNIBLE] AND PROPORTION 1740 01:16:16,880 --> 01:16:23,880 ARE PEDIATRIC A WILL. L. 1741 01:16:23,880 --> 01:16:24,520 LOOKING MOVING FORWARD EXPANSION 1742 01:16:24,520 --> 01:16:26,800 OF PRODUCTS AND INDICATIONS WE 1743 01:16:26,800 --> 01:16:29,880 SEE MORE OR LESS OF BREAKDOWN OF 1744 01:16:29,880 --> 01:16:33,600 240 REPORTED A YEAR FOR ALL AND 1745 01:16:33,600 --> 01:16:37,000 MOST ARE PEDIATRIC ALL. IS THIS 1746 01:16:37,000 --> 01:16:38,320 QUESTION TOTALITY HOW 1747 01:16:38,320 --> 01:16:40,440 REPRESENTATIVE IT IS FOR ACTUAL 1748 01:16:40,440 --> 01:16:44,440 NUMBER OF PATIENTS ELJEBL TO 1749 01:16:44,440 --> 01:16:49,640 RECEIVE IF IN RECEIVING PRODUCTS 1750 01:16:49,640 --> 01:16:55,600 AND NOVARTIS A YEAR AGO WE HAVE 1751 01:16:55,600 --> 01:17:00,800 70% REPRESENTATIVE OF CHEMOIA IN 1752 01:17:00,800 --> 01:17:01,840 UNITED STATES AND NEED 1753 01:17:01,840 --> 01:17:04,440 EVALUATION ONGOING TO SEE HOW 1754 01:17:04,440 --> 01:17:05,520 REPRESENTATIVE THESE REPORTS ARE 1755 01:17:05,520 --> 01:17:08,920 AND WITH DATA WE SEE CLEAR 1756 01:17:08,920 --> 01:17:12,200 INITIALLE PATTERNS YOU HEARD 1757 01:17:12,200 --> 01:17:14,440 FROM PREVIOUS SPEAKER REGINA 1758 01:17:14,440 --> 01:17:15,760 TALKED ABOUT PRIOR TRANSPLANT. 1759 01:17:15,760 --> 01:17:18,440 YOU SEE IT IS REALLY SHIFTING 1760 01:17:18,440 --> 01:17:20,440 AND PATIENTS COME TO CAR WITH 1761 01:17:20,440 --> 01:17:22,680 LESS PROPORTION OF PATIENTS 1762 01:17:22,680 --> 01:17:24,400 HAVING PRIOR [INDISCERNIBLE] AND 1763 01:17:24,400 --> 01:17:26,360 SEE IMPACT ON TRANSPLANTS THAT 1764 01:17:26,360 --> 01:17:30,160 ARE BEING DONE AND YOU SEE LAST 1765 01:17:30,160 --> 01:17:35,360 NUMBERS OF LYMPHOMA AND LOOK AT 1766 01:17:35,360 --> 01:17:40,400 SPECIFIC AND PEDIATRIC ALL AND 1767 01:17:40,400 --> 01:17:43,880 NUMBERS PEEKED IN 2019 AND 1768 01:17:43,880 --> 01:17:46,640 PATIENTS ARE COMING INTO CAR 1769 01:17:46,640 --> 01:17:49,680 MORE OFTEN WITH NEXT IMPACT AND 1770 01:17:49,680 --> 01:17:51,520 HOW IS USE OF RENLTRY LOOKING AT 1771 01:17:51,520 --> 01:17:54,400 FIRST SLIDE I SHOWED YOU AND 1772 01:17:54,400 --> 01:17:56,000 POTENTIAL USES WE ARE DOING THIS 1773 01:17:56,000 --> 01:17:58,520 AND DOING THIS POST 1774 01:17:58,520 --> 01:18:00,040 AUTHORIZATION AND WITH 1775 01:18:00,040 --> 01:18:00,800 COLLABORATING WITH MULTIPLE 1776 01:18:00,800 --> 01:18:02,800 CENTERS OUTSIDE OF THE US AS 1777 01:18:02,800 --> 01:18:04,720 WELL TO USE AS RESOURCE FOR 1778 01:18:04,720 --> 01:18:07,360 REGULATORY DATA COLLECTION AND 1779 01:18:07,360 --> 01:18:08,840 CREATED A PATTERN BECAUSE 1780 01:18:08,840 --> 01:18:10,640 PRODUCTS HAVE OFTEN TIMES 1781 01:18:10,640 --> 01:18:11,840 NON-CONFORMING AND WE HAVE A 1782 01:18:11,840 --> 01:18:14,120 PROCESS TO CAPTURE THIS WITHIN 1783 01:18:14,120 --> 01:18:16,040 DATABASE WITHOUT CREATING A 15 1784 01:18:16,040 --> 01:18:18,480 YEAR CLINICAL TRIAL FOR 1785 01:18:18,480 --> 01:18:20,640 NONCOMMERCIAL PRODUCTS THAT MEET 1786 01:18:20,640 --> 01:18:23,000 SPECIFICATIONS AND BUILD PATIENT 1787 01:18:23,000 --> 01:18:24,480 REPORTED OUTCOMES AND INTEGRATE 1788 01:18:24,480 --> 01:18:28,440 SAMPLE COLLECTIONS FOR PATIENTS 1789 01:18:28,440 --> 01:18:30,160 DEVELOPING SUBSEQUENT NEUROPLASM 1790 01:18:30,160 --> 01:18:32,440 IMPORTANT IN ADULT CASES AND IS 1791 01:18:32,440 --> 01:18:35,320 FOR ALL CAR T-CELLS AND USE DATA 1792 01:18:35,320 --> 01:18:37,520 FOR INTEGRATING AND TRYING TO 1793 01:18:37,520 --> 01:18:39,360 UNDERSTAND NEW PRODUCTS USING 1794 01:18:39,360 --> 01:18:45,600 THIS AS A CONTROL FOR THESE NEW 1795 01:18:45,600 --> 01:18:46,800 PRODUCTS COMING THROUGH USING 1796 01:18:46,800 --> 01:18:48,520 DATA AND REGISTRY FOR THAT. I 1797 01:18:48,520 --> 01:18:52,440 THINK WHAT WE WANTED TO PROMOTE 1798 01:18:52,440 --> 01:18:55,920 IS TRYING TO BUILD DATA AS A 1799 01:18:55,920 --> 01:18:58,680 RESOURCE OF GROUPS COMING 1800 01:18:58,680 --> 01:19:01,120 TOGETHER THAT IS SUPPORT AND WE 1801 01:19:01,120 --> 01:19:05,600 ARE INVESTED IN THIS IDEA 1802 01:19:05,600 --> 01:19:06,480 DECENTRALIZING DATA AND 1803 01:19:06,480 --> 01:19:07,880 [INDISCERNIBLE] DATA THAT SHARED 1804 01:19:07,880 --> 01:19:09,720 WITH US WITH COMMUNITY TO HELP 1805 01:19:09,720 --> 01:19:13,560 COLLECT IT AND WORKING COMMITTEE 1806 01:19:13,560 --> 01:19:15,480 STUDIES THAT IS CURRENTLY BEING 1807 01:19:15,480 --> 01:19:21,840 LED BY AMY MOSKOP IN OUR GROUP 1808 01:19:21,840 --> 01:19:23,520 JUST HOW THAT IS COMPARABLE THIS 1809 01:19:23,520 --> 01:19:27,520 IS LYMPHOMA AND LOOKING AT DATA 1810 01:19:27,520 --> 01:19:31,000 AND PIVOTAL TRIAL AS PD SIMILAR 1811 01:19:31,000 --> 01:19:33,680 OUTCOMES THAT IS PAPER WE 1812 01:19:33,680 --> 01:19:36,440 PUBLISH WITH YOU PRESENT ON IT 1813 01:19:36,440 --> 01:19:37,440 DEMONSTRATING COMPARABLE 1814 01:19:37,440 --> 01:19:39,880 EFFICACY ENDPOINTS AS WELL WITH 1815 01:19:39,880 --> 01:19:42,160 DATA THAT IS GOOD AND LOOKING AT 1816 01:19:42,160 --> 01:19:45,320 PATTERNS WE ARE LOOKING AT 1817 01:19:45,320 --> 01:19:47,560 LYMPHOMA AND DECREASE OF 1818 01:19:47,560 --> 01:19:52,400 PROPORTIONS OF PISHIENTS WITH 1819 01:19:52,400 --> 01:19:56,920 GREAT 3C ARE. S AS WELL AND WE 1820 01:19:56,920 --> 01:20:01,480 DON'T SEE WITH PEDIATRIC ALL 1821 01:20:01,480 --> 01:20:03,800 STEADY PROPORTION OF GRADE 3CRS 1822 01:20:03,800 --> 01:20:05,120 THAT IS RELATED TO THE DISEASE 1823 01:20:05,120 --> 01:20:08,040 AND SEEING A SHIFT FROM 2018 TO 1824 01:20:08,040 --> 01:20:10,680 2020 MEETING AGE OF PATIENTS HAS 1825 01:20:10,680 --> 01:20:12,560 BEEN INCREASING AND IS TO 1826 01:20:12,560 --> 01:20:13,960 ILLUSTRATE WITHIN THE DISEASE 1827 01:20:13,960 --> 01:20:15,320 AND PRODUCTS THERE IS 1828 01:20:15,320 --> 01:20:17,680 DISTRIBUTION OF DIFFERENT 1829 01:20:17,680 --> 01:20:21,240 OUTCOMES IN TERMS OF CRS AND 1830 01:20:21,240 --> 01:20:22,920 NEUROTOXICITY AND THIS MIGHT 1831 01:20:22,920 --> 01:20:26,000 ALSO BE RELEVANT HERE TRYING TO 1832 01:20:26,000 --> 01:20:26,800 BUILD COMORBIDITY COURSE TO 1833 01:20:26,800 --> 01:20:28,920 ASSESS IMPACT OF THIS IN OUTCOME 1834 01:20:28,920 --> 01:20:31,760 THAT IS ADULT LYMPHOMA AND THINK 1835 01:20:31,760 --> 01:20:35,160 SIMILAR EFFORTS IN ALL WILL BE 1836 01:20:35,160 --> 01:20:36,320 INTERESTING TO SELECT PATIENTS 1837 01:20:36,320 --> 01:20:39,880 MATTER THAT IS A EXAMPLE AND 1838 01:20:39,880 --> 01:20:41,000 NON-CONFORMING PRODUCTS USING 1839 01:20:41,000 --> 01:20:43,640 SAME PLATFORM AND PATIENTS 1840 01:20:43,640 --> 01:20:45,240 ENROLL AND EXPAND ACCESS 1841 01:20:45,240 --> 01:20:47,920 PROTOCOL TO TRY TO ENROLL THEM 1842 01:20:47,920 --> 01:20:49,160 GETTING INITIAL INFORMATION INTO 1843 01:20:49,160 --> 01:20:51,560 THEM AND EVENTUALLY ZERO HUNDRED 1844 01:20:51,560 --> 01:20:54,360 OR 30 DAYS THERE WILL BE A SHIFT 1845 01:20:54,360 --> 01:20:58,520 INTO THE LONG-TERM FOLLOW UP 1846 01:20:58,520 --> 01:21:02,960 PROTOCOL USING CMRT DATA 1847 01:21:02,960 --> 01:21:04,000 STRUCTURE AND MY SLIDE AND TO 1848 01:21:04,000 --> 01:21:06,440 WORK ON IT AND MORE THINGS WE 1849 01:21:06,440 --> 01:21:06,960 CAN DO. 1850 01:21:06,960 --> 01:21:09,440 I THINK USING PLATFORM FOR 1851 01:21:09,440 --> 01:21:11,840 REGULATORY APPROVAL OF NEWER 1852 01:21:11,840 --> 01:21:13,200 MODIFICATIONS OF PRODUCT MIGHT 1853 01:21:13,200 --> 01:21:15,520 BE GOAL FOR US NO THE TO GO BACK 1854 01:21:15,520 --> 01:21:18,080 ONLINE CREATING NEW CLINICAL 1855 01:21:18,080 --> 01:21:20,440 TRIALS AND WE WANT TO LEVERAGE 1856 01:21:20,440 --> 01:21:21,840 REGISTRY TO LOOK AT BIMARKER 1857 01:21:21,840 --> 01:21:24,520 DISCOVERY FINDING WAYS TO 1858 01:21:24,520 --> 01:21:26,680 INTEGRATE THIS WITH PATIENT 1859 01:21:26,680 --> 01:21:28,040 REPORTED OUTCOME AND FIELD 1860 01:21:28,040 --> 01:21:30,160 CONTINUING TO EVOLVE WE NEED TO 1861 01:21:30,160 --> 01:21:31,760 BE FLEXIBLE AND HAD TO CHANGE 1862 01:21:31,760 --> 01:21:36,440 SINCE TIME WE STARTED REGISTRY 1863 01:21:36,440 --> 01:21:38,280 DATA COLLECTION FORMS WERE 1864 01:21:38,280 --> 01:21:40,640 REVISED 10 TIMES AND TO 1865 01:21:40,640 --> 01:21:42,960 TESTAMENT TO HOW FAST A FIELD IS 1866 01:21:42,960 --> 01:21:44,440 MOVING AND HAVE TO BE FLEXIBLE 1867 01:21:44,440 --> 01:21:46,680 TO ALLOW THIS TO HAPPEN AND I'M 1868 01:21:46,680 --> 01:21:48,400 GLAD TO BE HERE SHARING 1869 01:21:48,400 --> 01:21:50,160 INFORMATION AND THIS IS ON 1870 01:21:50,160 --> 01:21:51,480 BEHALF OF LOTS OF PEOPLE AND 1871 01:21:51,480 --> 01:21:53,080 HAVE TO THANK THEM TO 1872 01:21:53,080 --> 01:21:54,480 PARTICIPATE AND THANK YOU FOR 1873 01:21:54,480 --> 01:21:58,480 LISTENING AND COLLABORATING WITH 1874 01:21:58,480 --> 01:22:05,400 REGISTRY. THANK YOU. 1875 01:22:05,400 --> 01:22:15,840 >> THANK YOU, MARCELO. 1876 01:22:19,400 --> 01:22:23,640 >> DO I NEED TO CLICK ANYTHING? 1877 01:22:23,640 --> 01:22:26,120 JACOBY AND I HAVE AN IMPOSSIBLE 1878 01:22:26,120 --> 01:22:28,120 TASK TO TALK ABOUT THE GLOBAL 1879 01:22:28,120 --> 01:22:30,160 EXPERIENCE OF CAR T-CELLS 1880 01:22:30,160 --> 01:22:31,520 WORLDWIDE. 1881 01:22:31,520 --> 01:22:34,280 SO, I'M JUST GOING TO SHARE WITH 1882 01:22:34,280 --> 01:22:36,000 YOU GLIMPSE AND THOUGHTS. IT IS 1883 01:22:36,000 --> 01:22:39,760 IMPOSSIBLE TO DO IT IN TIMEFRAME 1884 01:22:39,760 --> 01:22:42,280 THAT IS HERE. 1885 01:22:42,280 --> 01:22:44,640 SO, GLOBALLY LOOKING, THIS IS 1886 01:22:44,640 --> 01:22:47,840 LAST MONTH FROM CLINICAL 1887 01:22:47,840 --> 01:22:50,440 TRIALS.GOV AND NARROWING CAR 1888 01:22:50,440 --> 01:22:52,520 T-CELLS FOR ALL THERE IS 1889 01:22:52,520 --> 01:22:57,360 ACTIVITY THAT IS A LOT WORLDWIDE 1890 01:22:57,360 --> 01:23:00,440 OUT OF THE US WHETHER IN CHINA 1891 01:23:00,440 --> 01:23:04,280 OR EUROPE OR OTHER PLACES AND 1892 01:23:04,280 --> 01:23:07,720 WILL DIVIDE TALK INTO TWO PARTS 1893 01:23:07,720 --> 01:23:10,360 REAL-WORLD DATA COMING FROM 1894 01:23:10,360 --> 01:23:12,440 INTERNATIONAL TRIALS AND SECOND 1895 01:23:12,440 --> 01:23:14,200 LOOKING AT NOVEL CARS AND 1896 01:23:14,200 --> 01:23:17,680 DISCUSSES THAT A LITTLE BIT AND 1897 01:23:17,680 --> 01:23:20,240 T-CELLS WERE ONLY APPROVED CARS 1898 01:23:20,240 --> 01:23:23,400 FOR CHILDREN AND APPROVED IN 1899 01:23:23,400 --> 01:23:26,680 2018 IN EUROPE AND RECRUITMENT 1900 01:23:26,680 --> 01:23:28,400 FROM AUSTRALIA AND JAPAN AND 1901 01:23:28,400 --> 01:23:31,680 EUROPEAN COUNTRIES AND MAINLY 1902 01:23:31,680 --> 01:23:32,440 BECAUSE OF LOGISTICAL CHALLENGE 1903 01:23:32,440 --> 01:23:35,800 TO TRANSFER CELLS ACROSS OCEANS 1904 01:23:35,800 --> 01:23:36,560 MANUFACTURING SITES HAVE CHANGED 1905 01:23:36,560 --> 01:23:40,760 NOT JUST IN THE US. 1906 01:23:40,760 --> 01:23:41,560 MINOR BUT SIGNIFICANT 1907 01:23:41,560 --> 01:23:42,920 PARTICIPATION IN TRIAL OUTSIDE 1908 01:23:42,920 --> 01:23:47,600 OF THE US AND LOOKING AT SOME 1909 01:23:47,600 --> 01:23:48,960 REPORTS OF REAL WORLD DATA 1910 01:23:48,960 --> 01:23:50,840 COMING I WANT TO HIGHLIGHT TWO 1911 01:23:50,840 --> 01:23:52,440 THINGS I READ IN THESE PAPERS 1912 01:23:52,440 --> 01:23:54,520 FIRST COMING FROM US AND BOTTOM 1913 01:23:54,520 --> 01:23:58,200 COMING FROM OUTSIDE OF THE US 1914 01:23:58,200 --> 01:24:00,400 AND POPULATION IS SLIGHTLY 1915 01:24:00,400 --> 01:24:03,560 DIFFERENT AND LYMPHOMA ADULT 1916 01:24:03,560 --> 01:24:06,520 COLLEAGUES OBSERVED AS WELL 1917 01:24:06,520 --> 01:24:09,160 PATIENTS COMING FROM EUROPE MORE 1918 01:24:09,160 --> 01:24:11,680 HEAVILY TREATED AND EFFECTING 1919 01:24:11,680 --> 01:24:16,440 OUTCOMES AS WELL COMPARED TO 1920 01:24:16,440 --> 01:24:20,440 CONSORTIA OUTSIDE OF THE US AND 1921 01:24:20,440 --> 01:24:22,680 MRD MEASURED SIGNIFICANTLY 1922 01:24:22,680 --> 01:24:24,520 DIFFERENT FLOW CITOMETRY AND 1923 01:24:24,520 --> 01:24:29,640 MOST EUROPEAN COUNTRY PCR-BASED 1924 01:24:29,640 --> 01:24:32,040 MOVING TO NGS THAT MIGHT ALSO 1925 01:24:32,040 --> 01:24:34,280 IMPACT HOW WE LOOK AT RESULTS 1926 01:24:34,280 --> 01:24:38,800 AND WHAT IS TRUE MRD NEGATIVE 1927 01:24:38,800 --> 01:24:41,680 ACTIVITY POST CAR T-CELLS AND 1928 01:24:41,680 --> 01:24:43,160 PAPERS COMING FROM EUROPEAN 1929 01:24:43,160 --> 01:24:44,440 GROUPS THAT IS FIRST THAT 1930 01:24:44,440 --> 01:24:48,400 SHOWING YOU EARLIER COMING FROM 1931 01:24:48,400 --> 01:24:50,760 PARRIS GROUP AND LOOKING AT 1932 01:24:50,760 --> 01:24:53,400 PHENOTYPE OF RELAPSE AFTER CAR 1933 01:24:53,400 --> 01:24:54,920 T-CELLS AND YOU KNOW GENERAL 1934 01:24:54,920 --> 01:24:57,640 OBSERVATION THAT HIGH DISEASE 1935 01:24:57,640 --> 01:25:00,480 BURDEN LEADS TO POOR OUTCOME HAS 1936 01:25:00,480 --> 01:25:03,440 BEEN SEEN HERE. 1937 01:25:03,440 --> 01:25:05,880 INTERESTING THING IS CD19 1938 01:25:05,880 --> 01:25:08,440 POSITIVE RELAPSE WAS PATIENTS 1939 01:25:08,440 --> 01:25:10,440 THAT LOST B CELL APLASIA NOT 1940 01:25:10,440 --> 01:25:11,880 SURPRISING AND PATIENTS COMING 1941 01:25:11,880 --> 01:25:16,120 IN WITH LOWER DISEASE BURDEN 1942 01:25:16,120 --> 01:25:20,400 PATIENTS AND THAT IMPACTING CD19 1943 01:25:20,400 --> 01:25:22,200 POSITIVE RELAPSE SUGGESTING YOU 1944 01:25:22,200 --> 01:25:23,800 NEED SOME SORT OF DISEASE BURDEN 1945 01:25:23,800 --> 01:25:27,880 TO PROVIDE PERSISTENCE OF CELLS. 1946 01:25:27,880 --> 01:25:29,960 SECOND REPORT CAME OUT ECREPTLY 1947 01:25:29,960 --> 01:25:33,600 FROM GERMAN CONSORTIUM LED BY 1948 01:25:33,600 --> 01:25:33,840 PETER. 1949 01:25:33,840 --> 01:25:36,880 THEY LOOKED AT PROBLEM THAT MOST 1950 01:25:36,880 --> 01:25:38,320 PATIENTS THERE CAME AFTER 1951 01:25:38,320 --> 01:25:42,480 TRANSPLANT AND 80% OF PATIENTS 1952 01:25:42,480 --> 01:25:46,320 RECEIVING CAR T-CELLS IN 1953 01:25:46,320 --> 01:25:46,880 GERMANY. 1954 01:25:46,880 --> 01:25:49,440 THERE WAS NO SIGNIFICANT 1955 01:25:49,440 --> 01:25:51,760 DIFFERENCE WITH PATIENTS WITH 1956 01:25:51,760 --> 01:25:54,120 PRIOR TRANSPLANT AND LOOKING AT 1957 01:25:54,120 --> 01:25:55,640 TIMING OF RELAPSE POST 1958 01:25:55,640 --> 01:25:59,920 TRANSPLANT PATIENTS RELAPSED 6 1959 01:25:59,920 --> 01:26:01,640 MONTHS -- DID SIGNIFICANTLY 1960 01:26:01,640 --> 01:26:03,600 WORSE THAN PATIENTS HAVING LATER 1961 01:26:03,600 --> 01:26:05,400 RELAPSE MIGHT BE DUE TO 1962 01:26:05,400 --> 01:26:08,080 SELECTION BIAS OF VERY 1963 01:26:08,080 --> 01:26:10,440 AGGRESSIVE DISEASE OR POOR 1964 01:26:10,440 --> 01:26:12,440 T-CELL FUNCTIONALITY COLLECTING 1965 01:26:12,440 --> 01:26:14,160 T-CELLS IN FIRST 6 MONTHS AFTER 1966 01:26:14,160 --> 01:26:17,640 TRANSPLANT IS SOMETHING TO BE 1967 01:26:17,640 --> 01:26:20,040 DISCUSSED IN FURTHER RESEARCH. 1968 01:26:20,040 --> 01:26:21,800 THERE IS COLLABORATIVE EFFORTS 1969 01:26:21,800 --> 01:26:23,120 GOING TO BE DISCUSSED LATER IN 1970 01:26:23,120 --> 01:26:25,680 THE MEETING. I WILL HIGHLIGHT 1971 01:26:25,680 --> 01:26:28,920 THERE HAVE BEEN PKS LED BY 1972 01:26:28,920 --> 01:26:32,000 PRINCESS MAX MA GROUP AND CNS 1973 01:26:32,000 --> 01:26:34,600 CAR T-CELLS FOR CNS RELAPSE AND 1974 01:26:34,600 --> 01:26:38,360 IN INFANTS AND SOME MORE. 1975 01:26:38,360 --> 01:26:40,440 SWITCHING GEARS TO TALK ABOUT 1976 01:26:40,440 --> 01:26:43,560 CHERRY PICKING A FEW STUDIES 1977 01:26:43,560 --> 01:26:44,240 HIGHLIGHTING DIFFERENT CAR 1978 01:26:44,240 --> 01:26:45,720 CUBINGS AND HAVE A QUESTION I 1979 01:26:45,720 --> 01:26:46,720 THINK IS IMPORTANT TO DISCUSS 1980 01:26:46,720 --> 01:26:48,880 WHAT ARE LESSONS WE CAN LEARN 1981 01:26:48,880 --> 01:26:50,520 FROM STUDIES LOOKING AT 1982 01:26:50,520 --> 01:26:52,400 DIFFERENT CARS APPLYING IT TO 1983 01:26:52,400 --> 01:26:56,720 WHAT WE USE IN DAILY PRACTICE. 1984 01:26:56,720 --> 01:26:59,240 THERE IS A LOT OF THINGS GOING 1985 01:26:59,240 --> 01:27:02,760 ON AND WILL TALK ABOUT UK 1986 01:27:02,760 --> 01:27:04,160 EXPERIENCE FROM GOSH AND UCL AND 1987 01:27:04,160 --> 01:27:06,160 THERE IS INTERESTING DATA THAT 1988 01:27:06,160 --> 01:27:08,320 IS STILL A LITTLE PREMATURE 1989 01:27:08,320 --> 01:27:11,720 COMING FROM MULL 10Y CAR. 1990 01:27:11,720 --> 01:27:15,560 YOU SEE THESE REFERENCES FROM 1991 01:27:15,560 --> 01:27:16,520 CLAUDIA'S GROUP AND 1992 01:27:16,520 --> 01:27:19,000 [INDISCERNIBLE] GROUP AND WILL 1993 01:27:19,000 --> 01:27:20,440 TALK ABOUT EXPERIENCE WITH 1994 01:27:20,440 --> 01:27:22,000 [INDISCERNIBLE] ASSIMILATED CAR 1995 01:27:22,000 --> 01:27:24,480 AND ALL AND ABOUT SPANISH AND 1996 01:27:24,480 --> 01:27:28,400 ONE CHINESE EXAMPLE. 1997 01:27:28,400 --> 01:27:32,240 SO, UCL GOSH HAVE A SERIES OF 1998 01:27:32,240 --> 01:27:34,440 WONDERFUL PHASE 1 TRIALS FIRST 1999 01:27:34,440 --> 01:27:35,760 ONE LOOKING AT DIFFERENT BINDER 2000 01:27:35,760 --> 01:27:39,040 CAT BINDER LOW AFFINITY AND FAST 2001 01:27:39,040 --> 01:27:42,560 ON OFF RATE AND USE IN PHASE 1 2002 01:27:42,560 --> 01:27:45,360 TRIAL IN ALL LED BY SARAH AND 2003 01:27:45,360 --> 01:27:48,440 WONDERFUL CRA GOOD PERSISTENCE 2004 01:27:48,440 --> 01:27:53,600 AND HIGH RATE OF NEGATIVE 19 2005 01:27:53,600 --> 01:27:57,240 RELAPSE AND DOMAINS AND AGAIN CR 2006 01:27:57,240 --> 01:28:00,600 RATE IS FANTASTIC BUT 2007 01:28:00,600 --> 01:28:03,640 PERSISTENCE WAS POOR. 2008 01:28:03,640 --> 01:28:06,040 MOVING TO FURTHER CLINICAL 2009 01:28:06,040 --> 01:28:08,840 TRIALS IS -- YOU KNOW, THIS IS 2010 01:28:08,840 --> 01:28:14,120 AN EXCELLENT CAR BUT IN PHASE 1 2011 01:28:14,120 --> 01:28:16,280 TRIAL I WESH WAS IN CONSULTATION 2012 01:28:16,280 --> 01:28:20,320 OR COMMERCIALIZATION AND WE USED 2013 01:28:20,320 --> 01:28:22,880 CD28-BASED CARS AND LOOKED AT 2014 01:28:22,880 --> 01:28:26,240 EXTRA MEDULLARY DISEASE THAT IS 2015 01:28:26,240 --> 01:28:28,440 SUGGESTED FROM PEDIATRIC REAL 2016 01:28:28,440 --> 01:28:29,680 WORLD CONSORTIUM DOING WORSE 2017 01:28:29,680 --> 01:28:31,480 USING T-CELLS AND RESULTS ARE 2018 01:28:31,480 --> 01:28:34,640 OPPOSITE AND PATIENTS WITH EXTRA 2019 01:28:34,640 --> 01:28:38,000 MEDULLARY DISEASE AND BULKY DO 2020 01:28:38,000 --> 01:28:40,000 FANTASTIC WITH CD28 2021 01:28:40,000 --> 01:28:42,560 CO-ASSIMILATED CAR AND HAVE TO 2022 01:28:42,560 --> 01:28:43,200 BE CONSOLIDATED WITH TRANCE 2023 01:28:43,200 --> 01:28:45,800 PLANT PATIENTS AND NOT 2024 01:28:45,800 --> 01:28:47,200 CONSOLIDATED WHEN TRANSPLANT 2025 01:28:47,200 --> 01:28:49,080 DIDN'T DO WELL WHICH IS NOT 2026 01:28:49,080 --> 01:28:53,640 SURPRISING AND SPANISH GROUP HAD 2027 01:28:53,640 --> 01:28:55,920 AN EXPERIENCE WITH BASKET TRIAL 2028 01:28:55,920 --> 01:28:58,480 WITH NOVEMBEREL BINDER CALLED 2029 01:28:58,480 --> 01:29:00,320 REOO1 AND THEY RENTED BASKET 2030 01:29:00,320 --> 01:29:02,560 TRIAL OF 53 ADULTS AND CHILDREN 2031 01:29:02,560 --> 01:29:06,560 WITH ALL AND OBSERVED B CELL 2032 01:29:06,560 --> 01:29:07,640 MRASHIA AND DISEASE ARE 2033 01:29:07,640 --> 01:29:09,320 IMPORTANT AND TWO THINGS ARE I 2034 01:29:09,320 --> 01:29:11,080 THINK SHOULD BE HIGHLIGHTED FROM 2035 01:29:11,080 --> 01:29:12,280 THIS EXPERIENCE THAT IS 2036 01:29:12,280 --> 01:29:13,840 UNFORTUNATE THERE IS NO ONE FROM 2037 01:29:13,840 --> 01:29:15,560 THE GROUP AND MEETING AND HOPE 2038 01:29:15,560 --> 01:29:17,560 THEY WILL CONTINUE OR COME TO 2039 01:29:17,560 --> 01:29:18,280 FUTURE MEETINGS. 2040 01:29:18,280 --> 01:29:21,800 FIRST OF ALL WE SELL TOXICITY 2041 01:29:21,800 --> 01:29:25,480 INITIALLY MOVING TO THOSE 2042 01:29:25,480 --> 01:29:28,040 FRACTIONATED REJ P MENTED AND 2043 01:29:28,040 --> 01:29:30,840 60% DAY 2 IN CASE OF NO TOXICITY 2044 01:29:30,840 --> 01:29:32,320 AND SECOND THING THAT IS 2045 01:29:32,320 --> 01:29:34,080 IMPORTANT IS ACTUALLY THE FIRST 2046 01:29:34,080 --> 01:29:38,080 CAR T-CELL PRODUCT APPROVED FOR 2047 01:29:38,080 --> 01:29:39,920 USE BY REGULATORY AGENCY AND 2048 01:29:39,920 --> 01:29:42,560 ALSO IN CHILDREN WITH ALL AND 2049 01:29:42,560 --> 01:29:44,080 WAS UNDER THE HOSPITAL EXCEPTION 2050 01:29:44,080 --> 01:29:46,280 PATHWAY AND IS LOTS OF 2051 01:29:46,280 --> 01:29:47,560 REGULATORY CONSTRAINTS WE TALKED 2052 01:29:47,560 --> 01:29:49,480 ABOUT IN PRE-MEETINGS AND THERE 2053 01:29:49,480 --> 01:29:51,400 IS A LOT TO LEARN ABOUT HOW TO 2054 01:29:51,400 --> 01:29:56,000 TAKE NOVEL CAR TO APPROVAL 2055 01:29:56,000 --> 01:29:56,880 PROCESS. 2056 01:29:56,880 --> 01:29:59,920 LAST BUT NOT LEAST THERE IS TONS 2057 01:29:59,920 --> 01:30:02,480 OF DATA COMING FROM CHINA AND IS 2058 01:30:02,480 --> 01:30:04,880 COMPLEX TO LOOK AT IT DETAILS 2059 01:30:04,880 --> 01:30:13,440 ARE MISS IN MANY PAPERS RECENT 2060 01:30:13,440 --> 01:30:16,200 REVIEW OF HEEM ATOLL AND PHASE 1 2061 01:30:16,200 --> 01:30:20,360 AND PHASE 2 AND HIGHLIGHTING 2062 01:30:20,360 --> 01:30:24,400 LARGEST 1 COMING FROM GROUP IN 2063 01:30:24,400 --> 01:30:26,280 SHANGHAI AND PHASE 2 TRIAL 2064 01:30:26,280 --> 01:30:29,760 GIVING COMBINATION OF CD19 AND 2065 01:30:29,760 --> 01:30:32,200 CD22 CARS SAME TIME ONE-TO-ONE 2066 01:30:32,200 --> 01:30:36,440 RATIO WITH REALLY A MORE THAN 2067 01:30:36,440 --> 01:30:40,480 99% CR RATE AND GOOD EVENT 2068 01:30:40,480 --> 01:30:42,280 OVERALL SURVIVALS AND 40% OF 2069 01:30:42,280 --> 01:30:44,480 PASH YEVENTS WENT TO TRANSPLANT 2070 01:30:44,480 --> 01:30:47,080 AND RATE OF CD19 NEGATIVE 2071 01:30:47,080 --> 01:30:49,640 RELAPSE IN THE COHORT IS ABOUT 2072 01:30:49,640 --> 01:30:52,440 40% OF TOTAL PATIENTS RELAPSING 2073 01:30:52,440 --> 01:30:55,520 THAT IS SIMILAR TO WHAT WE SEE 2074 01:30:55,520 --> 01:30:58,000 WITH CD19 CAR. 2075 01:30:58,000 --> 01:31:00,880 SO, THIS I THIS I IS MY LAST 2076 01:31:00,880 --> 01:31:02,720 SLIDE. I THINK THERE ARE THREE 2077 01:31:02,720 --> 01:31:04,080 THINGS WE NEED TO TALK ABOUT AND 2078 01:31:04,080 --> 01:31:08,160 FIRST OF ALL HOW WE ACCESS AND 2079 01:31:08,160 --> 01:31:12,200 HOW WE ACCESS BETWEEN COMMERCIAL 2080 01:31:12,200 --> 01:31:15,120 CARS AND NOVEL TRIALS GETTING 2081 01:31:15,120 --> 01:31:17,880 ACCESS IN NON-US AND 2082 01:31:17,880 --> 01:31:18,960 NON-EUROPEAN COUNTRIES AND THIS 2083 01:31:18,960 --> 01:31:21,160 MAP IS HERE TO SHOW NO ACTIVITY 2084 01:31:21,160 --> 01:31:23,720 COMING IN AFRICA AND INDIA HAS 1 2085 01:31:23,720 --> 01:31:26,880 TRIAL STARTING WITH MEL 10Y 2086 01:31:26,880 --> 01:31:30,720 PLATFORM AND A LITTLE IN 2087 01:31:30,720 --> 01:31:31,960 SOUTHEAST ASIA AND ONE IN SOUTH 2088 01:31:31,960 --> 01:31:33,000 AMERICA AND MOST OF THE WORLD IS 2089 01:31:33,000 --> 01:31:36,400 NO THE HAVING ACCESS TO ANY CAR 2090 01:31:36,400 --> 01:31:38,560 T-CELLS WHATSOEVER THAT IS 2091 01:31:38,560 --> 01:31:39,840 INTERTWINED WITH COST OF THIS 2092 01:31:39,840 --> 01:31:40,640 PROCESS AND HAVE TO FIGURE OUT 2093 01:31:40,640 --> 01:31:42,840 AS A GROUP HOW TO REDUCE COST TO 2094 01:31:42,840 --> 01:31:44,720 GET ACCESS HIGHER AND WITH THIS 2095 01:31:44,720 --> 01:31:48,520 THANK YOU FOR LISTENING AND I'M 2096 01:31:48,520 --> 01:31:50,640 LOOKING FORWARD TO DISCUSSION 2097 01:31:50,640 --> 01:31:53,360 AND THIS WONDERFUL MEETING. 2098 01:31:53,360 --> 01:31:55,600 THANK YOU. 2099 01:31:55,600 --> 01:31:57,520 >> [APPLAUSE]. 2100 01:31:57,520 --> 01:31:59,440 >> THANK YOU. WITH IT THAT, 2101 01:31:59,440 --> 01:32:01,320 OPENING TO QUESTIONS AND PLEASE 2102 01:32:01,320 --> 01:32:05,160 APPROACH THE MICROPHONES AND ASK 2103 01:32:05,160 --> 01:32:10,760 YOUR QUESTIONS. 2104 01:32:10,760 --> 01:32:17,600 >> A COUPLE QUESTIONS. FIRST,LY 2105 01:32:17,600 --> 01:32:19,520 ORA. WITH DOSE ASSOCIATION I 2106 01:32:19,520 --> 01:32:21,880 WANT TO ASK SPECIFICALLY YOUR 2107 01:32:21,880 --> 01:32:23,400 THOUGHTS WHETHER THAT DOSE IS 2108 01:32:23,400 --> 01:32:25,320 TRULY DOSE OR A SIGN WHEN YOU 2109 01:32:25,320 --> 01:32:28,240 DID THE ORIGINAL EXPANSION 2110 01:32:28,240 --> 01:32:30,240 ASSOCIATED WITH CAR T 2111 01:32:30,240 --> 01:32:31,840 MANUFACTURING PROCESS YOU HAD 2112 01:32:31,840 --> 01:32:33,600 MORE FIT T-CELL AND HAD A BAG 2113 01:32:33,600 --> 01:32:36,080 WITH MORE IN IT AND SAY THIS AS 2114 01:32:36,080 --> 01:32:37,440 PRACTICAL CONSIDERATION BECAUSE 2115 01:32:37,440 --> 01:32:40,840 WHEN WE GET POOR EXPANSION WITH 2116 01:32:40,840 --> 01:32:44,000 THE CELL, YOU WON'T GET EXTRA 2117 01:32:44,000 --> 01:32:47,280 BAGS OR YOU WILL HAVE VERY LOW 2118 01:32:47,280 --> 01:32:47,480 BAGS. 2119 01:32:47,480 --> 01:32:49,440 WAS THE HIGHER DOSE -- IT 2120 01:32:49,440 --> 01:32:52,760 PROBABLY WAS ALL A SINGLE BAG; 2121 01:32:52,760 --> 01:32:53,040 RIGHT? 2122 01:32:53,040 --> 01:32:55,280 >> SORRY YEAH. THESE ARE VERY 2123 01:32:55,280 --> 01:32:56,280 EXCELLENT QUESTIONS. 2124 01:32:56,280 --> 01:32:59,560 SO, YOU KNOW, WE DEFINITELY HAVE 2125 01:32:59,560 --> 01:33:01,320 SOME KNOWLEDGE, EXPERIENTIAL 2126 01:33:01,320 --> 01:33:04,440 KNOWLEDGE THAT PATIENTS COMING 2127 01:33:04,440 --> 01:33:06,000 WITH HIGHER COUNT COLLECTION 2128 01:33:06,000 --> 01:33:10,120 MIGHT HAVE POORER FIT T-CELLS IN 2129 01:33:10,120 --> 01:33:12,760 MULTIVARIED ANALYSIS THAT DIDN'T 2130 01:33:12,760 --> 01:33:15,680 SHOW UP TO BE A CONFOUNDER AND 2131 01:33:15,680 --> 01:33:19,040 DOSE INDEPENDENTLY MATTERED IN 2132 01:33:19,040 --> 01:33:21,440 DISEASE BURDEN AND THAT IS 2133 01:33:21,440 --> 01:33:23,320 PERTINENT AND VANESSA IN THE 2134 01:33:23,320 --> 01:33:25,640 AUDIENCE HERE IS LOOKING AT A 2135 01:33:25,640 --> 01:33:28,160 BASELINE BLAST COUNT AND HOW IT 2136 01:33:28,160 --> 01:33:29,280 IMPACTS T-CELL FITNESS AND YOUR 2137 01:33:29,280 --> 01:33:32,920 QUESTION IS EXTRA ORDINARILY 2138 01:33:32,920 --> 01:33:33,960 PERTINENT BECAUSE ONE THING WE 2139 01:33:33,960 --> 01:33:36,760 DON'T HAVE SAMPLES TO LOOK AT 2140 01:33:36,760 --> 01:33:38,520 T-CELL FITNESS. YOU KNOW, WE 2141 01:33:38,520 --> 01:33:40,600 ARE SOMEWHAT, YOU KNOW, 2142 01:33:40,600 --> 01:33:40,960 RESTRAINED. 2143 01:33:40,960 --> 01:33:43,880 WE CAN'T ACTUALLY DO SOME OF THE 2144 01:33:43,880 --> 01:33:45,400 LABS THAT WE NEED TO DO SOME OF 2145 01:33:45,400 --> 01:33:47,760 THE TESTS AND STUDIES WE NEED TO 2146 01:33:47,760 --> 01:33:49,760 DO ON T-CELLS THEMSELVES THAT 2147 01:33:49,760 --> 01:33:53,280 WILL BE VERY HELPFUL IN 2148 01:33:53,280 --> 01:33:53,840 CLARIFYING HERE. 2149 01:33:53,840 --> 01:33:56,280 >> YEAH. ONE WAY TO KEEP IN 2150 01:33:56,280 --> 01:33:58,120 MIND STUDYING PROSPECTIVELY 2151 01:33:58,120 --> 01:34:02,400 IMPORTANT STUDY TO DO IS 2152 01:34:02,400 --> 01:34:04,440 DISTINGUISHING THOSE WHO HAD 2153 01:34:04,440 --> 01:34:07,320 ADEQUATE CELL DOSE WITH ONE BAG 2154 01:34:07,320 --> 01:34:09,600 VERSUS THOSE WHO TOOK 2 OR 3 2155 01:34:09,600 --> 01:34:12,280 BAGS, AGAIN, AS A SIGN OF POOR 2156 01:34:12,280 --> 01:34:14,680 FITNESS. WE HAD A MUCH LOWER 2157 01:34:14,680 --> 01:34:16,440 OVERALL EXPANSION AND WOULD LOVE 2158 01:34:16,440 --> 01:34:18,560 TO DO T-CELL FITNESS STUDIES AND 2159 01:34:18,560 --> 01:34:20,440 DON'T KNOW IF WE WILL BE ABLE TO 2160 01:34:20,440 --> 01:34:21,560 DO THOSE. YEAH? 2161 01:34:21,560 --> 01:34:23,240 >> DO WE KNOW WHAT IS IN THE 2162 01:34:23,240 --> 01:34:23,880 BAG? 2163 01:34:23,880 --> 01:34:26,600 >> NO. WE NEED TO KNOW WHAT IS 2164 01:34:26,600 --> 01:34:30,200 IN THE BAG FOR SURE. 2165 01:34:30,200 --> 01:34:33,680 >> SOMETIMES WE DO 2166 01:34:33,680 --> 01:34:34,360 [INDISCERNIBLE]. 2167 01:34:34,360 --> 01:34:36,040 >> [LAUGHING]. 2168 01:34:36,040 --> 01:34:36,920 >> [INDISCERNIBLE]. 2169 01:34:36,920 --> 01:34:40,360 >> YEAH. GO TO THE MIC, ANDRÉ. 2170 01:34:40,360 --> 01:34:42,360 YOUR WORDS ARE PEARLS SO. 2171 01:34:42,360 --> 01:34:45,560 >> I DON'T WANT TO HIJACK YOUR 2172 01:34:45,560 --> 01:34:45,880 QUESTIONS. 2173 01:34:45,880 --> 01:34:47,320 >> YOU ARE GOOD. 2174 01:34:47,320 --> 01:34:48,600 >> SAYING WHAT WE INFUSE WE 2175 01:34:48,600 --> 01:34:50,400 DON'T KNOW WHAT WE INFUSE. 2176 01:34:50,400 --> 01:34:50,960 >> YES. 2177 01:34:50,960 --> 01:34:54,600 >> THIS IS A BLACK BOX. THERE 2178 01:34:54,600 --> 01:34:57,800 IS A TRAVEL. THERE IS THAWING 2179 01:34:57,800 --> 01:35:00,840 THAT PROBABLY MODIFIES WHAT THE 2180 01:35:00,840 --> 01:35:02,320 SPECIFICATIONS ARE. IN FACT, WE 2181 01:35:02,320 --> 01:35:04,400 DON'T KNOW WHAT WE INFUSE AND 2182 01:35:04,400 --> 01:35:06,640 FOR SOME PATIENTS WHERE WE HAVE 2183 01:35:06,640 --> 01:35:10,040 NO EXPANSION, WE HAVE COMPARED 2184 01:35:10,040 --> 01:35:12,920 WHAT WE HAVE FOUNTD RINSING THE 2185 01:35:12,920 --> 01:35:17,240 BAG AFTER INFUSION TO WHAT WAS 2186 01:35:17,240 --> 01:35:20,560 SUPPOSED TO BE IN THE BAG 2187 01:35:20,560 --> 01:35:26,080 ACCORDING TO SPECIFICATION FROM 2188 01:35:26,080 --> 01:35:28,000 NEVARTIZ AND SDREPENCY WHAT WE 2189 01:35:28,000 --> 01:35:29,800 ARE INTERROGATING. 2190 01:35:29,800 --> 01:35:31,920 >> AND WISH WE COULD FIND A WAY 2191 01:35:31,920 --> 01:35:33,840 TO KNOW WHAT OUR PRODUCT REALLY 2192 01:35:33,840 --> 01:35:34,000 IS. 2193 01:35:34,000 --> 01:35:36,600 >> YEAH. TO ANDRÉ'S POINT WE 2194 01:35:36,600 --> 01:35:39,560 HAVE TRIED AND WRITTEN MULTIPLE 2195 01:35:39,560 --> 01:35:44,440 IRTS TO NEVARTIS AND WE HAVE HAD 2196 01:35:44,440 --> 01:35:45,080 MULTIPLE CONVERSATIONS. 2197 01:35:45,080 --> 01:35:45,520 >> THE SAME. 2198 01:35:45,520 --> 01:35:48,280 >> AND THEY ARE NOT AT THIS TIME 2199 01:35:48,280 --> 01:35:52,400 ABLE TO GIVE US SAMPLES AND 2200 01:35:52,400 --> 01:35:54,800 SURROGATE IS LOOKING AT AFORESIS 2201 01:35:54,800 --> 01:35:56,400 AND COLLABORATION TRYING TO 2202 01:35:56,400 --> 01:35:58,080 COLLECT AFOR EESIES THAT ARE 2203 01:35:58,080 --> 01:36:00,920 STORED IN INSTITUTIONAL BIOBANKS 2204 01:36:00,920 --> 01:36:02,640 TO CHARACTERIZE THESE. 2205 01:36:02,640 --> 01:36:05,000 REALLY, THE OTHER OPTION IS TO 2206 01:36:05,000 --> 01:36:06,840 COLLECT FROM THE BAG AND RINSE 2207 01:36:06,840 --> 01:36:09,160 THE BAG AND IT SOUNDS LIKE A 2208 01:36:09,160 --> 01:36:10,640 POOR OPTION. WE DON'T KNOW IF 2209 01:36:10,640 --> 01:36:12,640 WHAT WE GET IN THE BAG ARE WHAT 2210 01:36:12,640 --> 01:36:14,960 STICKS TO TUBES THAT IS ACTUALLY 2211 01:36:14,960 --> 01:36:17,280 REFLECTIVE WHAT GOES INTO THE 2212 01:36:17,280 --> 01:36:19,720 PATIENT OR SELECTION THERE. 2213 01:36:19,720 --> 01:36:22,160 >> COMMENTING ON THAT, IT IS NOT 2214 01:36:22,160 --> 01:36:22,440 ALLOWED. 2215 01:36:22,440 --> 01:36:22,880 >> YES. 2216 01:36:22,880 --> 01:36:24,240 >> THEY REALLY DON'T WANT TO 2217 01:36:24,240 --> 01:36:26,240 FIGURE OUT WHAT IS IN THE BAG. 2218 01:36:26,240 --> 01:36:30,080 IN OUR CONTRACT AND I KNOW THAT 2219 01:36:30,080 --> 01:36:32,640 THEY SAY A SPECIAL CONTRACT 2220 01:36:32,640 --> 01:36:34,840 BECAUSE OF SOME IP ISSUES I 2221 01:36:34,840 --> 01:36:36,360 DON'T WANT TO BRING UP. 2222 01:36:36,360 --> 01:36:38,720 >> DON'T READ THE CONTRACTS. 2223 01:36:38,720 --> 01:36:41,080 >> WE ARE FORBIDDEN TO RINSE THE 2224 01:36:41,080 --> 01:36:43,160 BAG AND DEVELOPED OUR -- WE 2225 01:36:43,160 --> 01:36:45,360 WANTED TO STUDY BAGS AND WE 2226 01:36:45,360 --> 01:36:47,640 DEVELOPED OUR OWN PRODUCT. 2227 01:36:47,640 --> 01:36:50,720 I'M ACTUALLY CURIOUS AS CENTERS 2228 01:36:50,720 --> 01:36:54,960 ARE YOU ALLOWED NOVARTIS 2229 01:36:54,960 --> 01:36:55,920 CONTRACT TO LOOK INTO THE BAG. 2230 01:36:55,920 --> 01:36:58,200 >> CENTERS AND ADULT COLLEAGUES 2231 01:36:58,200 --> 01:36:58,920 ARE DOG IT. 2232 01:36:58,920 --> 01:37:00,760 >> REFLECTION OF FACT WE DON'T 2233 01:37:00,760 --> 01:37:02,400 LOOK AT OUR CONTRACTS. 2234 01:37:02,400 --> 01:37:03,960 >> OTHER THING IS LIKE YOU KNOW. 2235 01:37:03,960 --> 01:37:05,240 >> I'M SERIOUS. 2236 01:37:05,240 --> 01:37:06,960 >> HE HAD AN INTERESTING 2237 01:37:06,960 --> 01:37:08,920 CHALLENGE COME UP HOW CAN WE 2238 01:37:08,920 --> 01:37:11,400 COLLECT BAGS? PHI IS IN BAGS 2239 01:37:11,400 --> 01:37:14,320 AND HOW DO WE REMOVE STICKERS TO 2240 01:37:14,320 --> 01:37:17,000 AVOID PHI AND OKAY LET'S GET 2241 01:37:17,000 --> 01:37:18,840 TUBING AND MAYBE THAT IS OUR OUT 2242 01:37:18,840 --> 01:37:21,680 THERE IS TUBING INCLUDED IN YOUR 2243 01:37:21,680 --> 01:37:24,000 CONTRACT? I THINK WE HAVE TO 2244 01:37:24,000 --> 01:37:31,640 FIGURE THIS OUT. IT IS A 2245 01:37:31,640 --> 01:37:34,160 MASSIVE GAP MISSING BIOLOGICAL 2246 01:37:34,160 --> 01:37:36,320 SIGNAL RINSING AND COLLECTING 2247 01:37:36,320 --> 01:37:37,920 CELLS MIGHT BE ANSWER AND WE 2248 01:37:37,920 --> 01:37:40,200 WILL PROBABLY GET INADEQUATE 2249 01:37:40,200 --> 01:37:41,760 SAMPLE IT THAT IS REALLY 2250 01:37:41,760 --> 01:37:43,400 DISAPPOINTING AT THIS PHASE IN 2251 01:37:43,400 --> 01:37:44,760 THE GAME WE CAN'T BE 2252 01:37:44,760 --> 01:37:47,240 CHARACTERIZING SAMPLES IN A 2253 01:37:47,240 --> 01:37:47,800 SYSTEMATIC WAY. 2254 01:37:47,800 --> 01:37:50,520 >> SOMETHING TO THINK ABOUT. 2255 01:37:50,520 --> 01:37:53,480 EACH MILL IS AT $30,000 AND 2256 01:37:53,480 --> 01:37:55,200 KEEPING THAT IN MIND. 2257 01:37:55,200 --> 01:37:59,280 LET'S SEE. MARCELO FOR CIDR, 2258 01:37:59,280 --> 01:38:01,840 HOW MANY PATIENTS ARE YOU 2259 01:38:01,840 --> 01:38:03,920 MISSING? 2260 01:38:03,920 --> 01:38:07,000 THIS IS A VOLUNTEER 2261 01:38:07,000 --> 01:38:07,760 ORGANIZATION. 2262 01:38:07,760 --> 01:38:09,800 IS THERE ANY WAY OR ANYONE DONE 2263 01:38:09,800 --> 01:38:11,160 A CALCULATION APPROXIMATELY HOW 2264 01:38:11,160 --> 01:38:12,520 MANY ARE MISSING? 2265 01:38:12,520 --> 01:38:14,880 I DON'T KNOW IF WE CAN EVEN DO 2266 01:38:14,880 --> 01:38:17,000 THAT BUT THINK YOU ARE MAYBE 2267 01:38:17,000 --> 01:38:19,240 GETTING HALF OF T-CELL OR OF 2268 01:38:19,240 --> 01:38:21,040 ALL. WHAT DO YOU THINK? 2269 01:38:21,040 --> 01:38:23,200 >> YES. THANK YOU, MIKE. 2270 01:38:23,200 --> 01:38:27,040 WAY WE DO IS WE KNOW DENOMINATOR 2271 01:38:27,040 --> 01:38:30,640 WHICH ARE SHIPPED PRODUCTS THAT 2272 01:38:30,640 --> 01:38:32,440 SOMETIMES IS DIFFICULT TO 2273 01:38:32,440 --> 01:38:34,000 EXTRACT THAT FROM THE COMPANY 2274 01:38:34,000 --> 01:38:36,320 AND THEY SAY PATIENTS HAVEN'T 2275 01:38:36,320 --> 01:38:37,840 SHARED CONSENT TO SHARE 2276 01:38:37,840 --> 01:38:38,720 INFORMATION AND RESPONSE IS TELL 2277 01:38:38,720 --> 01:38:40,680 ME YOU DON'T HAVE TO TELL ME 2278 01:38:40,680 --> 01:38:42,400 EXACTLY WHO DID OR WHO DID NOT 2279 01:38:42,400 --> 01:38:45,040 BUT TELL ME THE PERCENTAGES AND 2280 01:38:45,040 --> 01:38:48,880 WHEN WE DID WITH NOVARTIS WAS 2281 01:38:48,880 --> 01:38:53,120 70%. YOU SEE, THERE IS A TIME 2282 01:38:53,120 --> 01:38:55,040 LAG BETWEEN TIME THAT THEY GET 2283 01:38:55,040 --> 01:38:56,680 PRODUCT AND TIME CENTER WILL 2284 01:38:56,680 --> 01:38:59,400 REPORT TO US AND IS STILL A 2285 01:38:59,400 --> 01:39:00,560 VOLUNTARY PROCESS WE ARE MISSING 2286 01:39:00,560 --> 01:39:03,680 AND LOOKED AT BY CENTERS AND 2287 01:39:03,680 --> 01:39:06,520 VARIES FROM 0 TO 90% AND CENTERS 2288 01:39:06,520 --> 01:39:09,280 REPORT MOST CASES AND SOME 2289 01:39:09,280 --> 01:39:11,200 CENTERS DON'T REPORT ANY OF 2290 01:39:11,200 --> 01:39:11,560 THEM. 2291 01:39:11,560 --> 01:39:13,360 I THINK THAT FROM US WHAT WE DO 2292 01:39:13,360 --> 01:39:16,280 IS WE TRY TO UNDERSTAND. WE 2293 01:39:16,280 --> 01:39:18,760 WANT TO SEE FITNESS OF DATA AS 2294 01:39:18,760 --> 01:39:19,200 WELL. 2295 01:39:19,200 --> 01:39:21,000 SHOULD WE FIT OR INCLUDE 2296 01:39:21,000 --> 01:39:25,400 PATIENTS ON STUDIES THAT ONLY 2297 01:39:25,400 --> 01:39:27,240 REPORT 20% OF CHIMERA FOR 2298 01:39:27,240 --> 01:39:28,480 EXAMPLE WHAT IS THE SELECTION 2299 01:39:28,480 --> 01:39:30,640 THERE? YOU KNOW, WHO THEY ARE 2300 01:39:30,640 --> 01:39:32,440 REPORTING OR NOT REPORTING AND 2301 01:39:32,440 --> 01:39:33,680 IS REALLY EXTREMELY IMPORTANT 2302 01:39:33,680 --> 01:39:35,880 FOR US TO DO IT. WE ARE 2303 01:39:35,880 --> 01:39:38,040 OPERATING ON VOLUNTARY WORK AND 2304 01:39:38,040 --> 01:39:40,040 KNOW PEDIATRIC CENTERS TEND TO 2305 01:39:40,040 --> 01:39:42,280 REPORT MUCH BETTER THAN ADULT 2306 01:39:42,280 --> 01:39:45,160 CENTERS AND PROBABLY 10 OR 15% 2307 01:39:45,160 --> 01:39:46,600 GREATER AND BECAUSE, FOR 2308 01:39:46,600 --> 01:39:48,960 EXAMPLE, FOR KITE, IT IS ABOUT 2309 01:39:48,960 --> 01:39:51,520 60% FOR LYMPHOMA. SO, I THINK 2310 01:39:51,520 --> 01:39:53,720 THAT WE HAVE A FIFTH -- MORE 2311 01:39:53,720 --> 01:39:55,840 THAN 50% OF COMMERCIAL 2312 01:39:55,840 --> 01:39:57,720 REPRESENTATIVE HERE THAT VARIES 2313 01:39:57,720 --> 01:39:58,160 BY PRODUCT. 2314 01:39:58,160 --> 01:40:00,320 >> REASON I ASK THE QUESTION IS 2315 01:40:00,320 --> 01:40:01,840 TO BE PROVOCATIVE WOULD BE NICE 2316 01:40:01,840 --> 01:40:04,080 TO FIGURE OUT HOW TO NOT ONLY 2317 01:40:04,080 --> 01:40:05,680 GET BETTER REPORTING BUT WE NEED 2318 01:40:05,680 --> 01:40:07,440 MORE DATA TO ACTUALLY GET MOST 2319 01:40:07,440 --> 01:40:10,480 OF THE DATA IN. IT IS A BIG 2320 01:40:10,480 --> 01:40:12,320 CHALLENGE FOR YOU AND FOR ALL OF 2321 01:40:12,320 --> 01:40:12,480 US. 2322 01:40:12,480 --> 01:40:13,760 >> YEAH. 2323 01:40:13,760 --> 01:40:16,600 >> FINAL QUESTION TO REJENA. 2324 01:40:16,600 --> 01:40:20,440 SO, THIS IS A -- YOU KNOW, YOUR 2325 01:40:20,440 --> 01:40:22,040 OPINION AND I LOVE PEOPLE'S 2326 01:40:22,040 --> 01:40:23,480 COMMENTS IN THE AUDIENCE. 2327 01:40:23,480 --> 01:40:27,680 I AM REALLY INTRIGUED ABOUT 2328 01:40:27,680 --> 01:40:29,720 COMMENTS OF [INDISCERNIBLE] 2329 01:40:29,720 --> 01:40:31,040 WHERE DATA IS MIXED AND DON'T 2330 01:40:31,040 --> 01:40:33,000 KNOW WHAT TO DO WITH IT AND 2331 01:40:33,000 --> 01:40:36,120 CENTERS ARE WAITING UNTIL WE SEE 2332 01:40:36,120 --> 01:40:38,200 CD19 AND BELIEVE YOU NEED 2333 01:40:38,200 --> 01:40:41,880 SOMETHING FOR CELLS TO EXPAND 2334 01:40:41,880 --> 01:40:42,200 UPON. 2335 01:40:42,200 --> 01:40:44,920 HOW CAN WE GET WORD OUT TO 2336 01:40:44,920 --> 01:40:48,680 CENTERS OR FIGURE OUT HOW WE CAN 2337 01:40:48,680 --> 01:40:51,560 CONSISTENTLY HAVE A PREINFUSION 2338 01:40:51,560 --> 01:40:53,960 CD19 COUNT IN A WAY I WANT IT TO 2339 01:40:53,960 --> 01:40:58,560 BE PART OF CIDR DATA. 2340 01:40:58,560 --> 01:41:02,200 BUT, YOU KNOW, SEATTLE SHOWED 2341 01:41:02,200 --> 01:41:07,600 VERY NICE DATA AT CHLA DID THAT 2342 01:41:07,600 --> 01:41:09,720 AS WELL AND CONFIRMED DATA AND 2343 01:41:09,720 --> 01:41:11,320 IN FIELD WE HAVE TO FIGURE OUT 2344 01:41:11,320 --> 01:41:15,520 WHAT CD19 BURDEN IS AT TIME OF 2345 01:41:15,520 --> 01:41:17,240 INFUSION AND WHAT THOUGHTS ARE 2346 01:41:17,240 --> 01:41:18,960 ABOUT THAT REGINA. 2347 01:41:18,960 --> 01:41:20,920 >> IMPORTANT TO KNOW PERIPHERAL 2348 01:41:20,920 --> 01:41:22,800 AND BONE MARROW 19 YOU ARE MORE 2349 01:41:22,800 --> 01:41:23,560 INTERESTED IN. 2350 01:41:23,560 --> 01:41:26,320 >> I WILL TAKE EITHER ONE. I 2351 01:41:26,320 --> 01:41:27,000 DON'T CARE. 2352 01:41:27,000 --> 01:41:29,200 >> PERIPHERAL AND THIS WORK AND 2353 01:41:29,200 --> 01:41:31,680 TRYING TO GET STANDARDIZED 2354 01:41:31,680 --> 01:41:32,600 GUIDELINES TOGETHER AND HOW WE 2355 01:41:32,600 --> 01:41:34,600 CAN START TO PRACTICE A LITTLE 2356 01:41:34,600 --> 01:41:37,000 MORE SIMILARLY AND COMPARATIVE 2357 01:41:37,000 --> 01:41:41,160 DATA FOR CONSORTIUMS AND WAY TO 2358 01:41:41,160 --> 01:41:48,440 START TO GET PEOPLE TO DO THINGS 2359 01:41:48,440 --> 01:41:51,800 ON PULLING DATA AND ANTIGEN 2360 01:41:51,800 --> 01:41:54,640 BURDEN AND FOR US WE DO 2361 01:41:54,640 --> 01:41:57,400 PREINFUSION AND WE DON'T HAVE 2362 01:41:57,400 --> 01:41:59,080 ABILITY TO REPLICATE STUDIES YOU 2363 01:41:59,080 --> 01:42:04,640 DID AT SEATTLE. WE DO FOLLOW AT 2364 01:42:04,640 --> 01:42:07,800 LEAST FOR-I KNOW TWL ARE MORE 2365 01:42:07,800 --> 01:42:10,200 FUSIONS THAT HAVE PRIOR TO CARS 2366 01:42:10,200 --> 01:42:13,840 AND WE WILL START ABOUT 1 TO 2 2367 01:42:13,840 --> 01:42:17,040 MONTHS AND CHECKING CD19S ABOUT 2368 01:42:17,040 --> 01:42:19,560 EVERY 2 WEEKS OR SO TO SEE 2369 01:42:19,560 --> 01:42:22,200 RECOVERY AND GETTING PATIENTS TO 2370 01:42:22,200 --> 01:42:22,760 BE. 2371 01:42:22,760 --> 01:42:24,000 >> TO WHAT PERCENTAGE. 2372 01:42:24,000 --> 01:42:24,400 >> WHAT? 2373 01:42:24,400 --> 01:42:26,720 >> WHAT PERCENT ATH DO YOU 2374 01:42:26,720 --> 01:42:26,960 ACQUIRE? 2375 01:42:26,960 --> 01:42:29,000 >> WE HAVE EXACT NUMBER, I 2376 01:42:29,000 --> 01:42:30,520 THINK. THERE WAS DISCUSSION 2377 01:42:30,520 --> 01:42:32,880 YESTERDAY IT THAT WE HAVE 2378 01:42:32,880 --> 01:42:36,120 RECOVERY 3%. WE HAVEN'T SEEN 2379 01:42:36,120 --> 01:42:38,560 THAT SOMEWHERE BETWEEN 1% RISING 2380 01:42:38,560 --> 01:42:39,560 CLOSER TO THIS AND THERE ARE 2381 01:42:39,560 --> 01:42:45,720 TIMES WE GET TO FOUR MONTHS AND 2382 01:42:45,720 --> 01:42:48,440 DON'T SEE -- BONE MARROW SHOWING 2383 01:42:48,440 --> 01:42:50,120 EVIDENCE OF OVER 1 TO 2% AND 2384 01:42:50,120 --> 01:42:52,040 WILL GO AHEAD FROM THERE. 2385 01:42:52,040 --> 01:42:53,440 >> OKAY. MAKES SENSE. 2386 01:42:53,440 --> 01:42:54,200 IMPORTANT QUESTION? 2387 01:42:54,200 --> 01:42:56,400 >> I HAVE A QUESTION ABOUT THAT. 2388 01:42:56,400 --> 01:42:59,920 WE SOMETIMES GET SOME OF THE 2389 01:42:59,920 --> 01:43:00,680 REGULATOR QUESTIONS THROUGH 2390 01:43:00,680 --> 01:43:03,000 COMPANIES THAT THEY -- WE ARE 2391 01:43:03,000 --> 01:43:04,400 GETTING MORE OFTEN THESE 2392 01:43:04,400 --> 01:43:06,320 SPECIFIC QUESTIONS. HOW OFTEN 2393 01:43:06,320 --> 01:43:08,720 CENTERS ARE DOING CD19 AND 2394 01:43:08,720 --> 01:43:11,000 WHETHER TO INCORPORATE THAT IN 2395 01:43:11,000 --> 01:43:12,200 REGISTRY AND SOMETHING WE NEED 2396 01:43:12,200 --> 01:43:14,360 INPUT OF HOW OFTEN THIS IS DONE 2397 01:43:14,360 --> 01:43:17,800 AND HOW EASY IT IS COLLECTIBLE. 2398 01:43:17,800 --> 01:43:20,640 >> EASY TO INPUT AND DOING AS A 2399 01:43:20,640 --> 01:43:22,320 FIELD DECIDING WHAT WE WANT 2400 01:43:22,320 --> 01:43:25,920 COLLECTED CONSISTENTLY. IT IS 2401 01:43:25,920 --> 01:43:29,160 TRICKY PRE. AS REGINA MENTIONED 2402 01:43:29,160 --> 01:43:32,520 THERE IS PERIPHERAL PREAND BONE 2403 01:43:32,520 --> 01:43:36,960 MARROW PREAND PREPRIOR TO LD AND 2404 01:43:36,960 --> 01:43:38,800 PRE PRIOR TO INFUSION. WE ARE 2405 01:43:38,800 --> 01:43:40,400 NOT ALL ON THE SAME PAGE WITH 2406 01:43:40,400 --> 01:43:42,040 THAT. IT WOULD BE A NICE THING 2407 01:43:42,040 --> 01:43:45,880 FOR US TO THINK ABOUT THAT. 2408 01:43:45,880 --> 01:43:51,680 ALSO, WHEN WE DO IT FROM FLOW 2409 01:43:51,680 --> 01:43:53,640 FROM BONE MARROW WE DON'T HAVE 2410 01:43:53,640 --> 01:43:56,680 TO TELL PEOPLE BLASTS TOTAL CD19 2411 01:43:56,680 --> 01:43:58,320 FOR EVERYTHING AND RECALCULATING 2412 01:43:58,320 --> 01:44:00,520 HOW THEY DO THAT AND A BIT OF A 2413 01:44:00,520 --> 01:44:01,680 BURDEN TO FIGURE OUT AND 2414 01:44:01,680 --> 01:44:04,760 IMPORTANT THING FOR US TO 2415 01:44:04,760 --> 01:44:06,440 UNDERSTAND I THINK. 2416 01:44:06,440 --> 01:44:07,600 >> CLEARING ALL THAT CONFUSION 2417 01:44:07,600 --> 01:44:10,880 UP THIS SESSION IS OVER. HAVE A 2418 01:44:10,880 --> 01:44:11,600 BREAK NOW TAKE A QUICK BREAK. 2419 01:44:11,600 --> 01:44:15,200 11:15 WE WILL BE BACK. 2420 01:44:15,200 --> 01:44:26,760 WE WILL GET STARTED. 2421 01:44:26,760 --> 01:44:29,400 >> THANK YOU, STEVE, FOR 2422 01:44:29,400 --> 01:44:31,240 INTRODUCING AND GIVING THIS 2423 01:44:31,240 --> 01:44:35,280 TALK. JUST A JOKE, STEVE. I'M 2424 01:44:35,280 --> 01:44:37,680 TEASING. 2425 01:44:37,680 --> 01:44:46,600 SO, MY -- THE KEY TO DISCLOSURE 2426 01:44:46,600 --> 01:44:52,920 HERE IS SUPPORTING ADAPTIVE 2427 01:44:52,920 --> 01:44:53,160 ASSAYS. 2428 01:44:53,160 --> 01:44:57,520 I WANT TO FOCUS ON IN THIS 2429 01:44:57,520 --> 01:45:00,640 PARTICULAR TALK GOING INTO 2430 01:45:00,640 --> 01:45:04,240 DETAIL ABOUT GS THAT IS 2431 01:45:04,240 --> 01:45:07,120 IMPORTANT FOR US TO LEARN ABOUT 2432 01:45:07,120 --> 01:45:08,880 NGS. I WILL TRY TO DISTINGUISH 2433 01:45:08,880 --> 01:45:16,320 FOR EUROPEAN COLLEAGUES MAYBE 2434 01:45:16,320 --> 01:45:18,400 WHY GS MIGHT INFORM ABOUT 2435 01:45:18,400 --> 01:45:23,760 TECHNIQUES OF PCR. THIS IS NGS 2436 01:45:23,760 --> 01:45:27,320 IN THE BONE MARROW AND FLOW IN 2437 01:45:27,320 --> 01:45:28,200 IT. 2438 01:45:28,200 --> 01:45:31,240 NGS IS GETTING BELOW 10 TO THE 2439 01:45:31,240 --> 01:45:32,800 MINUS 4 CONSISTENTLY AND YOU 2440 01:45:32,800 --> 01:45:40,960 PICK UP 10 TO THE MINUS 5 WITH 2441 01:45:40,960 --> 01:45:42,680 PCR-BASED TECHNIQUES MISSING A 2442 01:45:42,680 --> 01:45:45,680 LOT OF PATIENTS AND THESE MATTER 2443 01:45:45,680 --> 01:45:51,080 AND NGRSMRD IN BLOOD AND FLOW IN 2444 01:45:51,080 --> 01:45:53,920 BONE MARROW YOU ARE MISSING AND 2445 01:45:53,920 --> 01:45:56,360 GETTING MORE PATIENTS WITH NGS 2446 01:45:56,360 --> 01:46:00,840 IN BLOOD THAN FLOW IN BONE 2447 01:46:00,840 --> 01:46:01,080 MARROW. 2448 01:46:01,080 --> 01:46:04,000 IMPORTANT OVENGS IN THIS STUDY 2449 01:46:04,000 --> 01:46:07,760 STEVE REFERRED TO EARLIER IS 2450 01:46:07,760 --> 01:46:09,640 THERE ARE TWO CONCEPTS TO 2451 01:46:09,640 --> 01:46:13,440 UNDERSTAND AND LIMITED DETECTION 2452 01:46:13,440 --> 01:46:20,240 AND THAT IS REALLY NOT REFERRING 2453 01:46:20,240 --> 01:46:21,760 TO WHETHER YOU CAN DETECT OR NOT 2454 01:46:21,760 --> 01:46:24,600 BUT REFERRING TO IF YOU REPEAT 2455 01:46:24,600 --> 01:46:26,880 SAMPLE 93% OF TIMES YOU WILL BE 2456 01:46:26,880 --> 01:46:29,040 ABLE TO DETECT IT. IN OTHER 2457 01:46:29,040 --> 01:46:35,640 WORDS IF YOU HAVE A LOW 2458 01:46:35,640 --> 01:46:39,280 FREQUENCY EVENT THAT IS THERE IN 2459 01:46:39,280 --> 01:46:45,400 THIS ASSAY, IT CAN BE TRUE NEXT 2460 01:46:45,400 --> 01:46:46,920 TIME YOU DO BONE MARROW YOU 2461 01:46:46,920 --> 01:46:50,640 WON'T NECESSARILY DETECT IT. IT 2462 01:46:50,640 --> 01:46:53,400 IS 1 IN 10 MILLION. 2463 01:46:53,400 --> 01:46:56,480 IF YOU LOOK AT SAMPLES, LIMITED 2464 01:46:56,480 --> 01:46:59,880 DETECTION CAN BE HIGH AND UP 2465 01:46:59,880 --> 01:47:04,960 HERE. 2466 01:47:04,960 --> 01:47:07,640 THAT IS BECAUSE OF SEQUENCES 2467 01:47:07,640 --> 01:47:10,960 USING FOR NGRS ARE NOT AS 2468 01:47:10,960 --> 01:47:12,720 SENSITIVE AS OTHERS AND BOTTOM 2469 01:47:12,720 --> 01:47:16,760 LINE THERE ARE DETECTIBLE 2470 01:47:16,760 --> 01:47:19,080 DISEASES THINGS ARE BELOW 2471 01:47:19,080 --> 01:47:20,560 LIMITED DETENTION AND LIMITED 2472 01:47:20,560 --> 01:47:23,280 QUANTITY FICTION AND WE FOUND A 2473 01:47:23,280 --> 01:47:28,640 PRETTY PROFOUND CUTOFF THAT WAS 2474 01:47:28,640 --> 01:47:30,200 BELOW WHAT YOU DO IF YOU LOOKED 2475 01:47:30,200 --> 01:47:33,280 AT PCR IF YOU LOOKED AT PCR AND 2476 01:47:33,280 --> 01:47:37,360 10 TO THE MINUS 6 THAT IS 2477 01:47:37,360 --> 01:47:39,440 SENSITIVE OF LIMITED DETECTION 2478 01:47:39,440 --> 01:47:40,800 AND QUANTITY IF IKS WE DIDN'T 2479 01:47:40,800 --> 01:47:43,000 SEE A DIFFERENCE BETWEEN THE TWO 2480 01:47:43,000 --> 01:47:45,040 AND WHY? PATIENTS TRULY 2481 01:47:45,040 --> 01:47:46,320 POSITIVE ARE PUT INTO THE 2482 01:47:46,320 --> 01:47:50,080 NEGATIVE CATEGORY AND IF YOU 2483 01:47:50,080 --> 01:47:56,440 LOOKED AT DETECTIBLE EVEN ONE 2484 01:47:56,440 --> 01:47:58,560 EVENT IN 10 MILLION HAD 2485 01:47:58,560 --> 01:47:59,920 PROGNOSTIC SIGNIFICANCE AND DATA 2486 01:47:59,920 --> 01:48:04,000 AT 28 DAYS AND AT TWLEE MONTHS 2487 01:48:04,000 --> 01:48:08,760 MEANING BY TIME YOU HAVE 3 2488 01:48:08,760 --> 01:48:12,280 MONTHS IF IGH CLONE THAT IS 2489 01:48:12,280 --> 01:48:14,520 POSITIVE 100% OF PATIENTS HAD 2490 01:48:14,520 --> 01:48:17,880 EVENT THAT IS SOMETHING TO KEEP 2491 01:48:17,880 --> 01:48:20,000 IN MIND SEEING THINGS AFTER CAR 2492 01:48:20,000 --> 01:48:24,720 THEY ARE MEANINGFUL. A COUPLE 2493 01:48:24,720 --> 01:48:27,840 THINGS TO UNDERSTAND HOW LONG IS 2494 01:48:27,840 --> 01:48:30,800 RELAPSE AND DISEASE DETECTING IT 2495 01:48:30,800 --> 01:48:35,240 AND HALF YOUR PATIENTS RELAPSED 2496 01:48:35,240 --> 01:48:37,920 PRIOR TO YOU BEING ABLE TO 2497 01:48:37,920 --> 01:48:40,760 DETECT THEM AND CUTOFF OF 10 TO 2498 01:48:40,760 --> 01:48:42,960 THE MINUS 6 AND QUARTER RELAPSED 2499 01:48:42,960 --> 01:48:44,360 BEFORE YOU DETECTED IT AND IF 2500 01:48:44,360 --> 01:48:46,480 YOU HAPPENED TO DETECT IT AND 2501 01:48:46,480 --> 01:48:48,600 THEY DIDN'T RELAPSE YOU HAD 2 2502 01:48:48,600 --> 01:48:50,240 MONTHS ON AVERAGE IF USING 2503 01:48:50,240 --> 01:48:52,600 CUTOFF OF 10 TO THE MINUS 6 AND 2504 01:48:52,600 --> 01:48:54,960 1 MONTH ON AVERAGE IF YOU USE 2505 01:48:54,960 --> 01:48:57,760 FLOW. BOTTOM LINE, YOU HAVE 2506 01:48:57,760 --> 01:48:58,840 VERY LITTLE TIME IF YOU USE 2507 01:48:58,840 --> 01:49:00,680 THESE TECHNIQUES AND IF YOU 2508 01:49:00,680 --> 01:49:03,280 CATCH IT VERY EARLY BELOW 10 TO 2509 01:49:03,280 --> 01:49:06,400 THE MINUS 6 CUTOFF WHERE YOU SEE 2510 01:49:06,400 --> 01:49:12,920 1 OR 2 EVENTS IN 10 MILLION ON 2511 01:49:12,920 --> 01:49:14,160 ADAPTIVE REPORT AND LESS THAN 0 2512 01:49:14,160 --> 01:49:16,120 YOU HAVE 6 MONTHS BEFORE 2513 01:49:16,120 --> 01:49:19,720 SOMETHING WILL HAPPEN 2514 01:49:19,720 --> 01:49:20,640 POTENTIALLY MEDIAN. 2515 01:49:20,640 --> 01:49:22,520 SO, IT IS IMPORTANT TO GAUGE 2516 01:49:22,520 --> 01:49:24,000 THAT AS YOU THINK ABOUT WHAT YOU 2517 01:49:24,000 --> 01:49:27,760 WILL DO IN ORDER TO RESPOND TO 2518 01:49:27,760 --> 01:49:32,680 YOUR MRD THESE CURVES ARE 2519 01:49:32,680 --> 01:49:34,280 IMPORTANT TO UNDERSTAND AND 2520 01:49:34,280 --> 01:49:35,440 QUALIFICATIONS FOR CURVE LOOKING 2521 01:49:35,440 --> 01:49:42,520 AT THIS LOSS OF B CELL AMRASHIA 2522 01:49:42,520 --> 01:49:46,200 YOU SEE PATIENTS LOST IT BEFORE 2523 01:49:46,200 --> 01:49:47,760 3 MONTHS HAD INCREDIBLY LOW 2524 01:49:47,760 --> 01:49:52,080 INCOME AND 6 MONTHS WITH 20% OR 2525 01:49:52,080 --> 01:49:56,800 ABOVE 20% HAVING DECENT SURVIVAL 2526 01:49:56,800 --> 01:49:59,080 AND BETWEEN 9 AND 6 MONTHS IS A 2527 01:49:59,080 --> 01:50:00,680 BIG QUESTION MARK I WANT TO HAVE 2528 01:50:00,680 --> 01:50:02,440 YOU TOTALLY DON'T BELIEVE THESE 2529 01:50:02,440 --> 01:50:04,600 TWO CURVES THAT ARE BASED ON 2530 01:50:04,600 --> 01:50:08,920 TOTAL OF 6 PATIENTS. OKAY? 2531 01:50:08,920 --> 01:50:15,160 SO, THEY MAY MEAN NOTHING. 2532 01:50:15,160 --> 01:50:16,760 TALKING ABOUT THINGS HERE WE 2533 01:50:16,760 --> 01:50:21,520 DON'T KNOW 9 TO 6 MONTHS AND 2534 01:50:21,520 --> 01:50:23,160 INTUITIVELY KEEPING IF YOU KEEP 2535 01:50:23,160 --> 01:50:25,640 THEM FOR 6 MONTHS AND WE DON'T 2536 01:50:25,640 --> 01:50:28,760 KNOW IF YOU SHOULD TRANSPLANT 2537 01:50:28,760 --> 01:50:32,000 EVERYONE LOSING B CELL APLASIA 2538 01:50:32,000 --> 01:50:34,440 AT 9 MONTHS AND SHOULD DO A 2539 01:50:34,440 --> 01:50:36,920 STUDY OR MORE AND KEEP IN MIND 6 2540 01:50:36,920 --> 01:50:38,640 TO 9 MONTH GROUPS AND NICE TO 2541 01:50:38,640 --> 01:50:42,160 SHOW PATIENTS GETTING TO 1 YEAR 2542 01:50:42,160 --> 01:50:44,720 AND HAVE B KRCHL APLASIA LONG 2543 01:50:44,720 --> 01:50:49,040 TERM SURVIVAL IS ABOUT 80% BASED 2544 01:50:49,040 --> 01:50:53,040 ON THIS DATA AND LEADS US TO 2545 01:50:53,040 --> 01:50:55,960 THIS TRIAL THAT WILL BE GONE 2546 01:50:55,960 --> 01:50:58,280 INTO IN GREAT DETAIL AND BOTTOM 2547 01:50:58,280 --> 01:50:59,760 LINE SCREENING INTENSELY TO SEE 2548 01:50:59,760 --> 01:51:02,120 IF AND WHEN WE SHOULD ACT ON IT 2549 01:51:02,120 --> 01:51:06,440 AND TRANSPLANT IS AN OPTION FOR 2550 01:51:06,440 --> 01:51:11,880 THOSE PATIENTS THAT BECOME 2551 01:51:11,880 --> 01:51:15,720 POSITIVE OR LOSE BC APLASIA AND 2552 01:51:15,720 --> 01:51:25,320 GIVE DETAIL ABOUT THAT 2553 01:51:25,320 --> 01:51:27,280 MENTIONING HOW I TREAT PUBLISHED 2554 01:51:27,280 --> 01:51:32,160 NOW AND YOU CAN HOPEFULLY REFER 2555 01:51:32,160 --> 01:51:32,440 TO THIS. 2556 01:51:32,440 --> 01:51:37,320 THIS IS WRONG ONE. I APOLOGIZE 2557 01:51:37,320 --> 01:51:39,280 AND I SENT UPDATED SLIDE AND 2558 01:51:39,280 --> 01:51:43,560 THINK I HAVE A COUPLE MINUTES 2559 01:51:43,560 --> 01:51:43,760 LEFT. 2560 01:51:43,760 --> 01:51:49,080 I WILL TALK ABOUT IN THE LAST 2561 01:51:49,080 --> 01:51:54,160 MINUTE OR SO ABOUT CAVEATS OF 2562 01:51:54,160 --> 01:51:56,400 NGS MONITORING AND LONG AND 2563 01:51:56,400 --> 01:52:00,760 SHORT IS THAT SENSITIVITY AND 2564 01:52:00,760 --> 01:52:04,280 SPECIFICITY OF NEXT GEN SEQUENCE 2565 01:52:04,280 --> 01:52:07,240 MONITORING IS RELATED TO HOW 2566 01:52:07,240 --> 01:52:09,280 MANY RECOMBINATIONS OR VDJ 2567 01:52:09,280 --> 01:52:15,640 RECOMBINATIONS YOU HAVE OR TCR 2568 01:52:15,640 --> 01:52:17,840 RECOMBINATIONS AND IF YOU HAVE 2569 01:52:17,840 --> 01:52:22,200 HEAVY CHAIN IGH YOU HAVE IN MOST 2570 01:52:22,200 --> 01:52:26,080 CASES IVS AND IDJ AND LOTS OF JS 2571 01:52:26,080 --> 01:52:29,080 AND YOU HAVE HIGH SENSITIVITY 2572 01:52:29,080 --> 01:52:31,520 AND LOTS OF POSSIBILITY FOR 2573 01:52:31,520 --> 01:52:33,040 REARRANGEMENTS AND LIKELY TO 2574 01:52:33,040 --> 01:52:34,200 NATURALLY REPLICATE SOMETHING 2575 01:52:34,200 --> 01:52:36,280 THAT IS SAME AS YOUR MRAFT. IF 2576 01:52:36,280 --> 01:52:38,480 YOU HAVE LIGHT CHAINS YOU WON'T 2577 01:52:38,480 --> 01:52:42,920 HAVE D OR WON'T HAVE V AND G AND 2578 01:52:42,920 --> 01:52:45,280 USUALLY MUCH LESS KEEP IN MIND 2579 01:52:45,280 --> 01:52:46,920 LIGHT CHAINS ARE NOT AS 2580 01:52:46,920 --> 01:52:50,520 SENSITIVE AS HEAVY CHAINS CAPPA 2581 01:52:50,520 --> 01:52:55,080 OR LAMBDA KEEP IN MIND SAME WITH 2582 01:52:55,080 --> 01:52:59,120 TCR GAMMA AND BETA TCR GAMMA IS 2583 01:52:59,120 --> 01:53:01,720 WORSE THAN TCR BETA AND BOTTOM 2584 01:53:01,720 --> 01:53:04,000 LINE JUST NOT AS MUCH 2585 01:53:04,000 --> 01:53:05,920 REARRANGEMENTS IF CAPPA OR GAMMA 2586 01:53:05,920 --> 01:53:09,240 OR TCR GAMMA THAT YOUR 2587 01:53:09,240 --> 01:53:10,960 REARRANGEMENTS ARE NOT VALID? 2588 01:53:10,960 --> 01:53:15,760 NO. DOESN'T MEAN THAT AT ALL. 2589 01:53:15,760 --> 01:53:20,080 IT MEANS IF YOU HAVE ONE MARKER 2590 01:53:20,080 --> 01:53:23,720 BE SUSPICIOUS OF IT. MIGHT BE 2591 01:53:23,720 --> 01:53:24,880 BACKGROUND NOISE IN THAT CASE. 2592 01:53:24,880 --> 01:53:26,840 WHAT SHOULD YOU DO? 2593 01:53:26,840 --> 01:53:29,280 REPEAT. IF YOU GET A SECOND 2594 01:53:29,280 --> 01:53:32,080 MARKER AND ALL OF US GETTING NGS 2595 01:53:32,080 --> 01:53:33,000 THINGS AT VERY BEGINNING AND 2596 01:53:33,000 --> 01:53:35,240 THREE MARKERS YOU ARE GREAT AND 2597 01:53:35,240 --> 01:53:36,120 HOPEFULLY YOU WILL HAVE MORE 2598 01:53:36,120 --> 01:53:37,800 THAN THREE MARKERS AND IF YOU 2599 01:53:37,800 --> 01:53:40,280 GET A SECOND MARKER THAT 2600 01:53:40,280 --> 01:53:42,600 EMERGES, YOU SHOULD ABSOLUTELY 2601 01:53:42,600 --> 01:53:45,920 BELIEVE IT AND IF YOU HAVE 2TCR 2602 01:53:45,920 --> 01:53:49,160 MARKERS OR TWO CAPPA OR LAMBDA 2603 01:53:49,160 --> 01:53:50,000 MARKERS. 2604 01:53:50,000 --> 01:53:51,840 BOTTOM LINE YOU CAN IF YOU GET A 2605 01:53:51,840 --> 01:53:55,520 SINGLE MARKER ESPECIALLY IF NOT 2606 01:53:55,520 --> 01:53:57,280 IG HEAVY CHAIN BESUSPICIOUS OF 2607 01:53:57,280 --> 01:53:59,880 IT AND REPEAT IT AND IF RISING 2608 01:53:59,880 --> 01:54:02,080 YOU MIGHT WANT TO BELIEVE IT IF 2609 01:54:02,080 --> 01:54:04,080 LOW AND STEADY WE FOLLOW A LOT 2610 01:54:04,080 --> 01:54:06,400 LIKE THAT AND MIGHT NOT BE REAL 2611 01:54:06,400 --> 01:54:08,360 ESPECIALLY IF OTHER MARKERS YOU 2612 01:54:08,360 --> 01:54:12,720 HAD PREVIOUSLY ARE NOT SHOWING 2613 01:54:14,160 --> 01:54:14,240 UP. 2614 01:54:14,240 --> 01:54:15,760 IMPORTANT CAVEATS FOR YOU TO 2615 01:54:15,760 --> 01:54:17,920 MAKE SURE TO REPEAT IT AND MAKE 2616 01:54:17,920 --> 01:54:19,160 SURE ABOUT IT AND WHEN PROVING 2617 01:54:19,160 --> 01:54:20,600 IT IS TRUE YOU CAN TAKE YOUR 2618 01:54:20,600 --> 01:54:24,520 ACTION AND THAT IS ALL I HAVE. 2619 01:54:24,520 --> 01:54:28,280 THANK YOU. 2620 01:54:28,280 --> 01:54:30,360 >> [APPLAUSE]. 2621 01:54:30,360 --> 01:54:32,400 >> >> WE HAVE SHEENA TALKING 2622 01:54:32,400 --> 01:54:34,600 ABOUT THE HUMANIZED CAR NEXT. 2623 01:54:34,600 --> 01:54:38,240 THANK YOU VERY MUCH. I WILL 2624 01:54:38,240 --> 01:54:41,760 TALK ABOUT THE EXPERIENCE THAT 2625 01:54:41,760 --> 01:54:45,400 IS AVAILABLE WITH HUMANIZED CAR. 2626 01:54:45,400 --> 01:54:47,600 THESE ARE DISCLOSURES THAT ARE 2627 01:54:47,600 --> 01:54:50,280 RELEVANT TO THIS TALK. I WILL 2628 01:54:50,280 --> 01:54:52,840 START OFF BY JUST A BRIEF 2629 01:54:52,840 --> 01:54:55,000 BACKGROUND OF WHY WE THINK ABOUT 2630 01:54:55,000 --> 01:54:57,320 CHANGING CARS THAT WE HAVE 2631 01:54:57,320 --> 01:54:59,360 AVAILABLE NOW. AS YOU ALL KNOW, 2632 01:54:59,360 --> 01:55:03,560 MOST OF THE CARS INITIALLY 2633 01:55:03,560 --> 01:55:07,440 DEVELOPED WERE DEVELOPED WITH 2634 01:55:07,440 --> 01:55:09,480 DOMAINS OF [INDISCERNIBLE] 2635 01:55:09,480 --> 01:55:10,760 ORIGIN AND THERE WAS A 2636 01:55:10,760 --> 01:55:11,800 HYPOTHESIS FROM THE BEGINNING 2637 01:55:11,800 --> 01:55:15,000 THAT IS POSSIBLE THAT YOU COULD 2638 01:55:15,000 --> 01:55:19,640 SEE ANTIMOUSE IMMUNE REJECTION 2639 01:55:19,640 --> 01:55:24,800 OF T-CELLS WE AND OTHERS THOUGHT 2640 01:55:24,800 --> 01:55:28,080 THROUGH DEVELOPING HUMANIZED OR 2641 01:55:28,080 --> 01:55:31,160 FULLY HUMAN DOMAINS AND REASON 2642 01:55:31,160 --> 01:55:33,360 FOR THAT INITIAL EXPERIENCE WITH 2643 01:55:33,360 --> 01:55:36,520 CAR T-CELLS YOU SEE DEPENDING ON 2644 01:55:36,520 --> 01:55:38,400 PRODUCT DIFFERENT LENGTH 2645 01:55:38,400 --> 01:55:39,880 PERSISTENCE WE KNOW AND LEARNED 2646 01:55:39,880 --> 01:55:42,920 OVER TIME DEPENDING ON 2647 01:55:42,920 --> 01:55:43,640 COSTIMULATORY DOMAIN YOU CAN SEE 2648 01:55:43,640 --> 01:55:46,040 DIFFERENT LENGTHS OF PERSISTENCE 2649 01:55:46,040 --> 01:55:49,880 WITH CD28 PRODUCTS EXPANDING 2650 01:55:49,880 --> 01:55:51,360 MORE RAPIDLY BUT NOT PERSISTING 2651 01:55:51,360 --> 01:55:56,920 AS LONG AS 41BB PRODUCTS 2652 01:55:56,920 --> 01:55:58,040 PERSISTING LONGER. EVEN WITHIN 2653 01:55:58,040 --> 01:56:02,480 ONE PRODUCT, YOU CAN SEE 2654 01:56:02,480 --> 01:56:03,440 DIFFERENT PERSISTENCE BASED ON 2655 01:56:03,440 --> 01:56:05,600 WHAT YOU SEE IN EACH PATIENT. 2656 01:56:05,600 --> 01:56:07,560 WHY IS THAT IMPORTANT? 2657 01:56:07,560 --> 01:56:11,600 WELL, WE -- AND OTHERS HAVE 2658 01:56:11,600 --> 01:56:15,240 LEARNED OVER TIME THAT 2659 01:56:15,240 --> 01:56:17,400 PERSISTENCE PARTICULARLY FOR 1BB 2660 01:56:17,400 --> 01:56:19,440 CONTAINING PRODUCTS WHERE YOU 2661 01:56:19,440 --> 01:56:20,800 TYPICALLY WILL SEE LONGER 2662 01:56:20,800 --> 01:56:24,360 PERSISTENCE IT THAT IS REALLY 2663 01:56:24,360 --> 01:56:26,520 IMPORTANT FOR DURABLE EMISSIONS 2664 01:56:26,520 --> 01:56:33,480 AND MIKE SHOWED YOU DATA FROM 2665 01:56:33,480 --> 01:56:36,920 ELION AND ENSON TRIALS AND FROM 2666 01:56:36,920 --> 01:56:38,360 SEATTLE GROUP AND FROM OUR GROUP 2667 01:56:38,360 --> 01:56:40,200 I WILL SHOW YOU THAT PATIENTS 2668 01:56:40,200 --> 01:56:44,160 THAT HAVE EARLY LOSS OF CD19 CAR 2669 01:56:44,160 --> 01:56:46,720 T-CELL PERSISTENCE MARKED AND 2670 01:56:46,720 --> 01:56:50,880 MEASURED BY EARLY B CELL 2671 01:56:50,880 --> 01:56:54,040 RECOVERY HAD HIGHER RISK OF 2672 01:56:54,040 --> 01:56:59,480 RELAPSE AND SEEING CD19 POSITIVE 2673 01:56:59,480 --> 01:57:01,200 RELAPSE AND THAT DISEASE WASN'T 2674 01:57:01,200 --> 01:57:04,880 CLEARED IN PATIENTS WITH LONG 2675 01:57:04,880 --> 01:57:06,120 TERM PERSISTENCE IT COULD COME 2676 01:57:06,120 --> 01:57:06,320 BACK. 2677 01:57:06,320 --> 01:57:07,840 WHAT WE AND OTHERS HAD DONE WAS 2678 01:57:07,840 --> 01:57:11,800 THINK ABOUT HOW WE COULD 2679 01:57:11,800 --> 01:57:14,480 POTENTIALLY OVERCOME THAT. 2680 01:57:14,480 --> 01:57:19,680 ON RATIONALE THAT IS RELATED TO 2681 01:57:19,680 --> 01:57:22,720 IMMUNE MEDIATED REJECTION THAT 2682 01:57:22,720 --> 01:57:26,640 SCF DOMAIN WE DID TRIAL WITH 2683 01:57:26,640 --> 01:57:29,720 HUMANIZED CAR 19 BASED ON 2684 01:57:29,720 --> 01:57:32,760 ORIGINAL MURINE CAR AND SCF 2685 01:57:32,760 --> 01:57:37,760 DOMAIN TO LOOK MORE LIKE HUMAN 2686 01:57:37,760 --> 01:57:38,920 PROTEIN AND DID THIS WITHOUT 2687 01:57:38,920 --> 01:57:41,400 KNOWING IF IT WAS REASON FOR 2688 01:57:41,400 --> 01:57:44,160 POOR PERSISTENCE AND MAJORITY OF 2689 01:57:44,160 --> 01:57:48,640 PATIENTS AND LOOKED AT PATIENTS 2690 01:57:48,640 --> 01:57:52,240 PREVIOUSLY RECEIVING CAR 2691 01:57:52,240 --> 01:57:54,480 RETREATMENT COHORT AND OPENED TO 2692 01:57:54,480 --> 01:57:56,440 PATIENTS NO THE RECEIVING CAR 2693 01:57:56,440 --> 01:57:58,680 LEFT COLUMN CAR NAÏVE AND 2694 01:57:58,680 --> 01:58:00,440 DEMOGRAPHICS OF PHASE 1 STUDY WE 2695 01:58:00,440 --> 01:58:04,160 DID IN THIS. I WANT TO POINT 2696 01:58:04,160 --> 01:58:06,680 OUT THAT MANY PATIENTS WERE 2697 01:58:06,680 --> 01:58:08,480 HEAVILY PRETREATED AND WE HAD A 2698 01:58:08,480 --> 01:58:11,240 LOWER DISEASE BURDEN THAT WAS 2699 01:58:11,240 --> 01:58:12,840 GOING INTO THIS TRIAL. 2700 01:58:12,840 --> 01:58:16,240 AND BASED ON REFERRAL PATTERNS 2701 01:58:16,240 --> 01:58:20,160 AND ELIANA TRIAL ENROLLING AT 2702 01:58:20,160 --> 01:58:22,480 SAME TIME AS THIS AND THAT IS TO 2703 01:58:22,480 --> 01:58:24,760 NOTE WHEN LOOKING AT TOXICITY 2704 01:58:24,760 --> 01:58:25,200 DATA. 2705 01:58:25,200 --> 01:58:30,600 THIS IS TOXICITY WE SAW IN THE 2706 01:58:30,600 --> 01:58:31,000 TRI 2707 01:58:31,000 --> 01:58:31,240 TRIAL. 2708 01:58:31,240 --> 01:58:33,520 WHAT I'M HIGHLIGHTING HERE IS 2709 01:58:33,520 --> 01:58:36,480 CRS AND WE SAW SIMILAR RATES 2710 01:58:36,480 --> 01:58:39,240 OVERALL OF CRS AND LOWER RATES 2711 01:58:39,240 --> 01:58:44,360 OF GRADE 3 AND 4CRS IN BOTH CAR 2712 01:58:44,360 --> 01:58:46,720 NIE EF AND CAR RETREATMENT 2713 01:58:46,720 --> 01:58:49,040 COHORT BEARING IN MIND PATIENTS 2714 01:58:49,040 --> 01:58:50,600 HAD LOWER DISEASE BURDEN GOING 2715 01:58:50,600 --> 01:58:51,120 IN. 2716 01:58:51,120 --> 01:58:52,880 THIS WAS CERTAINLY AS SAFE AS 2717 01:58:52,880 --> 01:58:56,960 WHAT WE SAW WITH THE MURINE 2718 01:58:56,960 --> 01:58:57,200 PRODUCT. 2719 01:58:57,200 --> 01:59:01,200 WITH NEUROTOXICITY WE SAW ALSO 2720 01:59:01,200 --> 01:59:04,840 LOWER RATES OF GRADE 3 AND 4 AND 2721 01:59:04,840 --> 01:59:07,200 NEUROTOXICITY IN RETREATMENT 2722 01:59:07,200 --> 01:59:09,520 COHORT KNOW GRADE 3 AND 4 2723 01:59:09,520 --> 01:59:10,080 NEUROTOXICITY. 2724 01:59:10,080 --> 01:59:13,160 WORD ABOUT THE EFFICACY. IT IS 2725 01:59:13,160 --> 01:59:16,720 IN THIS GROUP OF PATIENTS AND 2726 01:59:16,720 --> 01:59:20,720 I'M SHOWING YOU TWO DIFFERENT 2727 01:59:20,720 --> 01:59:23,240 RELAPSED FREE SURVIVAL CURVES 2728 01:59:23,240 --> 01:59:25,880 HERE AND ONE FOR RETREATMENT 2729 01:59:25,880 --> 01:59:29,800 COHORT IN RED AND COHORT IN 2730 01:59:29,800 --> 01:59:32,480 BLUE. IN RETREATMENT COHORT WE 2731 01:59:32,480 --> 01:59:35,200 SAW INITIAL CR RATE WAS 79% IN 2732 01:59:35,200 --> 01:59:37,360 THIS GROUP OF PATIENTS HOWEVER 2733 01:59:37,360 --> 01:59:38,840 MANY OF THESE PATIENTS ACTUALLY 2734 01:59:38,840 --> 01:59:40,800 CAME TO US IN REMISSION AND 2735 01:59:40,800 --> 01:59:44,520 MIGHT HAVE BEEN REFERRED FOR 2736 01:59:44,520 --> 01:59:47,680 POOR PERSISTENCE WITHOUT HAVING 2737 01:59:47,680 --> 01:59:48,560 HAD A RELAPSE. 2738 01:59:48,560 --> 01:59:51,400 WHAT WE LOOKED AT FOR OVERALL 2739 01:59:51,400 --> 01:59:56,120 RESPONSE WE DEFINED AS CR WITH B 2740 01:59:56,120 --> 02:00:00,760 CELL EPLASIA SHOWING LOW 2741 02:00:00,760 --> 02:00:02,440 BIOACTIVITY IN CAR AND THAT 2742 02:00:02,440 --> 02:00:04,360 OVERALL RATE WAS 64% AND WE SAW 2743 02:00:04,360 --> 02:00:06,880 IN TERMS OF RELAPSE FREE 2744 02:00:06,880 --> 02:00:08,200 SURVIVAL IN THAT GROUP WAS 2745 02:00:08,200 --> 02:00:10,240 PRETTY ENCOURAGING. I WILL SHOW 2746 02:00:10,240 --> 02:00:11,920 YOU WHAT PERSISTENCE LOOKED 2747 02:00:11,920 --> 02:00:15,720 LIKE. IT WAS SHORTER BUT WE 2748 02:00:15,720 --> 02:00:19,480 STILL WERE ABLE TO ACHIEVE A 2749 02:00:19,480 --> 02:00:21,240 FAIRLY GOOD RELAPSE FREE 2750 02:00:21,240 --> 02:00:24,520 SURVIVAL OF 74% OF 12 MONTHS AND 2751 02:00:24,520 --> 02:00:29,520 58% AT 24 MONTHS IN THIS GROUP 2752 02:00:29,520 --> 02:00:31,360 AND CAR NAÏVE GROUP WAS 2753 02:00:31,360 --> 02:00:34,160 ENCOURAGING AS WELL LOOKING AT 2754 02:00:34,160 --> 02:00:35,760 INITIAL RESPONSE RATE AND CR 2755 02:00:35,760 --> 02:00:39,160 RATE WAS 98% AND RELAPSE FREE 2756 02:00:39,160 --> 02:00:42,520 SURVIVAL AT 12 MONTHS WAS 84% 2757 02:00:42,520 --> 02:00:45,680 AND 24 MONTHS WAS 74% AND 2758 02:00:45,680 --> 02:00:47,120 ENCOURAGING IN HIGHER NUMBERS WE 2759 02:00:47,120 --> 02:00:50,280 HAD SEEN ON INITIAL PHASE 1 2760 02:00:50,280 --> 02:00:52,040 CHILD MURINE CAR. THESE 2761 02:00:52,040 --> 02:00:55,120 POPULATIONS AS I MENTIONED ARE 2762 02:00:55,120 --> 02:00:57,760 NOT COMPLETELY COMPARABLE. 2763 02:00:57,760 --> 02:00:59,880 I THINK SEEING MORE PATIENTS 2764 02:00:59,880 --> 02:01:02,560 WITH LOWER DISEASE BURDEN MAY 2765 02:01:02,560 --> 02:01:04,320 PARTIALLY ACCOUNT FOR THIS AND 2766 02:01:04,320 --> 02:01:05,680 CURRENTLY ARE CONDUCTING PHASE 2 2767 02:01:05,680 --> 02:01:08,880 TRIAL TO TRY TO HOPE TO MATCH UP 2768 02:01:08,880 --> 02:01:10,640 PATIENTS TO SEE IF RATES ARE 2769 02:01:10,640 --> 02:01:13,280 REALLY BETTER THAB WHAT WE HAVE 2770 02:01:13,280 --> 02:01:14,640 SEEN WITH MURINE. 2771 02:01:14,640 --> 02:01:16,760 MAIN OBJECTIVE OF THIS IS TO SEE 2772 02:01:16,760 --> 02:01:21,440 CAN WE IMPROVE PERSISTENCE? 2773 02:01:21,440 --> 02:01:25,200 WHAT I'M SHOWING HERE IS QPCR 2774 02:01:25,200 --> 02:01:27,280 DATA FROM THIS ON LEFT AND 2775 02:01:27,280 --> 02:01:29,240 RETREATMENT COHORT ON RIEBLTH 2776 02:01:29,240 --> 02:01:31,680 AND SEE IN CAR NAÏVE GROUP THERE 2777 02:01:31,680 --> 02:01:33,520 ARE SIGNIFICANT FRACTION OF 2778 02:01:33,520 --> 02:01:34,920 PATIENTS THAT HAVE PERSISTENCE 2779 02:01:34,920 --> 02:01:39,600 OUT TO 1 YEAR OR EVEN OUT TO 2 2780 02:01:39,600 --> 02:01:42,600 YEARS WHICH IS WHAT THIS GRAPH 2781 02:01:42,600 --> 02:01:44,120 EXTENDS OUT TO. RETREATMENT 2782 02:01:44,120 --> 02:01:46,560 GROUP THERE IS A LOWER NUMBER OF 2783 02:01:46,560 --> 02:01:51,160 PATIENTS WHO HAVE THAT EXTENDED 2784 02:01:51,160 --> 02:01:51,560 PERSISTENCE. 2785 02:01:51,560 --> 02:01:54,840 WE DID SEE PATIENTS WHO HAD POOR 2786 02:01:54,840 --> 02:01:56,600 PERSISTENCE IN THE PAST WERE 2787 02:01:56,600 --> 02:01:59,240 MUCH MORE LIKELY TO HAVE POOR 2788 02:01:59,240 --> 02:02:02,080 PERSISTENCE WITH HUMANIZED CAR 2789 02:02:02,080 --> 02:02:03,440 AS WELL. 2790 02:02:03,440 --> 02:02:06,680 THAT ARGUES AGAINST IMMUNE 2791 02:02:06,680 --> 02:02:08,120 MEDIATED REJECTION PHENOMENON 2792 02:02:08,120 --> 02:02:09,920 THAT IS PROBABLY NOT TRUE FOR 2793 02:02:09,920 --> 02:02:11,800 EVERYBODY. IT IS LIKELY TRUE 2794 02:02:11,800 --> 02:02:15,400 FOR SOME PATIENTS. 2795 02:02:15,400 --> 02:02:18,000 WE HAD A NUMBER OF PATIENTS IT 2796 02:02:18,000 --> 02:02:20,560 THAT RESPOND TO RETREATMENT AND 2797 02:02:20,560 --> 02:02:22,120 REINFUSION AND HAVE POOR 2798 02:02:22,120 --> 02:02:23,560 PERSISTENCE AGAIN AND WHY WE 2799 02:02:23,560 --> 02:02:26,080 STARTED TO GET INTO COMBINING 2800 02:02:26,080 --> 02:02:28,760 THAT WITH CHECKPOINT BLOCKADE. 2801 02:02:28,760 --> 02:02:32,760 SO WE DID SEE A FEW PATIENTS YOU 2802 02:02:32,760 --> 02:02:35,000 CAN SEE THAT DID HAVE EXTENDED 2803 02:02:35,000 --> 02:02:37,880 REALLY LONG PERSISTENCE WITH 2804 02:02:37,880 --> 02:02:40,600 RETREATMENT WITH HUMANIZED CAR. 2805 02:02:40,600 --> 02:02:43,040 IN SOME PATIENCE THIS MIGHT DO 2806 02:02:43,040 --> 02:02:45,560 THE TRICK AND IN PATIENTS LOSING 2807 02:02:45,560 --> 02:02:47,920 PERSISTENCE EARLY TO GO BACK TO 2808 02:02:47,920 --> 02:02:53,080 RELAPSE FREE SURVIVAL WE WERE 2809 02:02:53,080 --> 02:02:54,200 ABLE TO OVERCOME THAT WITH 2810 02:02:54,200 --> 02:02:57,200 REINFUSION IN MANY CASES TO 2811 02:02:57,200 --> 02:02:59,520 IMPROVE THAT RELAPSE FREE 2812 02:02:59,520 --> 02:03:01,320 SURVIVAL LONG TERM THAT IS 2813 02:03:01,320 --> 02:03:04,960 ENCOURAGING AND SHOWS US WE HAVE 2814 02:03:04,960 --> 02:03:06,080 ROOM TO GO WITH THIS. 2815 02:03:06,080 --> 02:03:08,800 NEXT QUESTION THAT I THINK IS 2816 02:03:08,800 --> 02:03:12,040 PROBABLY A KEY QUESTION THAT IS 2817 02:03:12,040 --> 02:03:17,160 GOING FORWARD IS NOT ONLY CAN WE 2818 02:03:17,160 --> 02:03:20,520 OVERCOME POOR PERSISTENCE IF IN 2819 02:03:20,520 --> 02:03:23,520 RETREATMENT GROUP CAN WE IMPROVE 2820 02:03:23,520 --> 02:03:26,600 CAR T PERSISTENCE MOVING NEEDLE 2821 02:03:26,600 --> 02:03:29,440 FORWARD AND FIELD FORWARD. WE 2822 02:03:29,440 --> 02:03:30,800 DID ANAL SIZE THAT THERE WASN'T 2823 02:03:30,800 --> 02:03:34,760 POWER TO LOOK AT THIS WE DID 2824 02:03:34,760 --> 02:03:38,480 COMPARISON OF CAR NAÏVE GROUP 2825 02:03:38,480 --> 02:03:41,200 WITH INITIAL PHASE 1 TRIAL. 2826 02:03:41,200 --> 02:03:43,960 THIS IS NOT STATISTICALLY 2827 02:03:43,960 --> 02:03:45,720 SIGNIFICANT IN TERMS OF 2828 02:03:45,720 --> 02:03:49,040 DIFFERENCE EFFECT SIZE IS 2829 02:03:49,040 --> 02:03:51,600 SUGGESTIVE. WE ONLY SEE 15% 6 2830 02:03:51,600 --> 02:03:53,160 MONTH PROBABILITY OF B CELL 2831 02:03:53,160 --> 02:03:55,760 RECOVERY IN HUMANIZED CAR NAÏVE 2832 02:03:55,760 --> 02:04:00,800 GROUP COMPARED TO 29% OF MURINE 2833 02:04:00,800 --> 02:04:02,440 PRODUCT AND WARRANTS STUDY 2834 02:04:02,440 --> 02:04:05,760 SEEING IF WE DO THIS FROM OUTSET 2835 02:04:05,760 --> 02:04:08,440 CAN WE IMPROVE UPON PERSISTENCE? 2836 02:04:08,440 --> 02:04:11,760 THERE IS SEVERAL OTHER GROUPS 2837 02:04:11,760 --> 02:04:17,080 THAT HAVE EXPLORED HUMAN OR 2838 02:04:17,080 --> 02:04:20,720 HUMANIZED CAR. 2839 02:04:20,720 --> 02:04:24,320 SNIPPETS HERE THANK YOU COURTESY 2840 02:04:24,320 --> 02:04:27,560 OF CLEAN. 2841 02:04:27,560 --> 02:04:28,360 GIVING BRIEF INFORMATION ON 2842 02:04:28,360 --> 02:04:33,680 THESE STUDIES THEY STUDIED FULLY 2843 02:04:33,680 --> 02:04:36,200 HUMAN FC DOMAIN AND PRIMIARILY 2844 02:04:36,200 --> 02:04:41,720 FOR PATIENTS WITH CD19 AFTER CAR 2845 02:04:41,720 --> 02:04:46,080 INCLUDED PATIENTS WITH B CELL 2846 02:04:46,080 --> 02:04:49,080 RECOVERY WITHIN 12 MONTHS AND 2847 02:04:49,080 --> 02:04:51,280 LATER WAS AMENDED TO EXCLUDE 2848 02:04:51,280 --> 02:04:54,080 THAT. THERE WAS SOME UNEXPECT 2849 02:04:54,080 --> 02:04:55,720 INCREASED TOXICITY SEEN IN THE 2850 02:04:55,720 --> 02:04:58,360 TRIAL THAT ENDED UP CLOSING 2851 02:04:58,360 --> 02:04:59,280 EARLY. 2852 02:04:59,280 --> 02:05:02,320 THE NCI HAS ALSO DEVELOPED A 2853 02:05:02,320 --> 02:05:05,520 FUELLY HUMAN CD19 CAR WITH CD20 2854 02:05:05,520 --> 02:05:08,120 DOMAIN AND MATCHES MORE CLOSELY 2855 02:05:08,120 --> 02:05:09,840 THEIR INITIAL MUIR EVEN PRODUCT 2856 02:05:09,840 --> 02:05:12,520 AND THEY DID A PHASE 1 TRIAL IN 2857 02:05:12,520 --> 02:05:14,560 ADULTS WITH NIHL AND SHOWING 2858 02:05:14,560 --> 02:05:17,840 GOOD CR RATE OF 55% IN 20 2859 02:05:17,840 --> 02:05:19,320 PATIENTS AND IN THE GRAPH AT 2860 02:05:19,320 --> 02:05:21,240 BOTTOM THAT IS EVENT FREE 2861 02:05:21,240 --> 02:05:23,760 SURVIVAL THAT IS REALLY PRETTY 2862 02:05:23,760 --> 02:05:26,040 COMPARABLE TO WHAT WAS SEEN WITH 2863 02:05:26,040 --> 02:05:29,320 MURINE PRODUCT AND OF NOTE THEY 2864 02:05:29,320 --> 02:05:32,360 HAD SEEN A HIGHER RATE OF 2865 02:05:32,360 --> 02:05:34,280 NEUROTOXICITY WITH MURINE CD19 2866 02:05:34,280 --> 02:05:38,720 CAR AND ON THIS TRIAL SAW 2867 02:05:38,720 --> 02:05:42,680 ACTUALLY SEVERE NEUROTOXICITY. 2868 02:05:42,680 --> 02:05:44,920 INTERESTINGLY WHAT WE ARE 2869 02:05:44,920 --> 02:05:48,120 GETTING AT WITH CAR IT THEY DID 2870 02:05:48,120 --> 02:05:52,080 STUDIES OF CAR T-CELL RESPONSES 2871 02:05:52,080 --> 02:05:56,800 AND SAW THAT LOWER CAR LEVELS 2872 02:05:56,800 --> 02:05:59,240 AND WE DID NOT SEE THAT WITH 2873 02:05:59,240 --> 02:06:04,560 HUMAN CARS SUGGESTING THAT. SO, 2874 02:06:04,560 --> 02:06:07,240 IN INTEREST OF TIME I CAN'T GO 2875 02:06:07,240 --> 02:06:12,880 OVER ALL HUMANIZED CAR SHOWING 2876 02:06:12,880 --> 02:06:23,240 REPORTS AND VARIOUS. 2877 02:07:14,320 --> 02:07:24,760 CAR HUMANIZED 19 TO GO WE MAY 2878 02:07:26,240 --> 02:07:35,120 SEE IMPROVEMENTS. SO THANK YOU 2879 02:07:35,120 --> 02:07:40,760 TO EVERYONE INVOLVED AND FOR 2880 02:07:40,760 --> 02:07:51,240 EVERYONE ORGANIZING THIS. 2881 02:07:58,640 --> 02:08:02,240 >> THANK YOU FOR BRINGING ME 2882 02:08:02,240 --> 02:08:12,480 HERE TODAY. 2883 02:08:25,200 --> 02:08:35,600 OUT OF OUR INSTITUTION -- 2884 02:08:50,480 --> 02:08:52,400 HOWEVER WHEN YOU FURTHER 2885 02:08:52,400 --> 02:08:56,080 SUBDIVIDE PATIENT POPULATION 2886 02:08:56,080 --> 02:08:59,880 THIS PATIENT POPULATION DIDN'T 2887 02:08:59,880 --> 02:09:10,200 REALLY SEEM TO -- 2888 02:09:34,280 --> 02:09:36,400 41BB DOMAIN 21 PATIENTS 2889 02:09:36,400 --> 02:09:38,600 PROCEEDED THE TRANSPLANT IN 26 2890 02:09:38,600 --> 02:09:40,040 DID NOT FOLLOWING REMISSION AND 2891 02:09:40,040 --> 02:09:42,200 YOU CAN SEE FOR EVENT FREE 2892 02:09:42,200 --> 02:09:44,800 SURVIVAL AND NOTED RELAPSE FREE 2893 02:09:44,800 --> 02:09:46,720 SURVIVAL IMPROVEMENT SHOWN IN 2894 02:09:46,720 --> 02:09:48,680 THE RED ON LEFT COMPARED TO 2895 02:09:48,680 --> 02:09:50,400 THOSE WHO DIDN'T PROCEED TO 2896 02:09:50,400 --> 02:09:51,880 TRANSPLANT IN GREEN AS WELL. 2897 02:09:51,880 --> 02:09:54,320 THERE IS A TREND TOWARDS 2898 02:09:54,320 --> 02:10:00,480 IMPROVED OVERALL SURVIVAL ON THE 2899 02:10:00,480 --> 02:10:10,920 RIGHT. IT DIDN'T REACH. 2900 02:10:31,320 --> 02:10:31,600 PR 2901 02:10:31,600 --> 02:10:33,080 WITHIN THIS PATIENT POPULATION 2902 02:10:33,080 --> 02:10:35,600 THEY DID SEE IMPROVEMENT AND 2903 02:10:35,600 --> 02:10:37,920 OVERALL SURVIVAL. THOUGH THEY 2904 02:10:37,920 --> 02:10:40,840 ARE LONG-TERM FOLLOW UP IS 2905 02:10:40,840 --> 02:10:51,320 SOMEWHAT LIMITED IN REPORT. 2906 02:11:09,240 --> 02:11:11,760 I THINK THAT IS LIKELY BECAUSE 2907 02:11:11,760 --> 02:11:15,040 THE CD28 CO-STEM IS LIKELY TO 2908 02:11:15,040 --> 02:11:17,320 PROVIDE LONG-TERM PERSISTENCE 2909 02:11:17,320 --> 02:11:22,680 COMPARED TO 41BB AND NOT ALL 2910 02:11:22,680 --> 02:11:24,480 STUDIES SHOW IMPROVEMENT 2911 02:11:24,480 --> 02:11:26,880 FOLLOWING CD19 CAR AND REPORT 2912 02:11:26,880 --> 02:11:32,920 FROM 2018 AND ADULT COHORT OF 44 2913 02:11:32,920 --> 02:11:43,440 PATIENTS AND SURVIVAL ON THE 2914 02:11:44,520 --> 02:11:48,400 RIGHT AGAIN OVERLAPPING CURVES 2915 02:11:48,400 --> 02:11:55,800 AND 6. 2916 02:11:55,800 --> 02:11:57,800 TRANSPLANT COHORT. EVEN STILL 2917 02:11:57,800 --> 02:11:59,800 OVERALL SURVIVAL IMPROVED WITH 2918 02:11:59,800 --> 02:12:02,560 TRANSPLANT FOLLOWING CD19 CARS 2919 02:12:02,560 --> 02:12:05,920 NOT BEING CONSISTENTLY OBSERVED 2920 02:12:05,920 --> 02:12:10,080 DATA FROM COHORT OF PATIENTS 2921 02:12:10,080 --> 02:12:10,920 TRANSPLANT PATIENTS WERE NOT 2922 02:12:10,920 --> 02:12:12,520 [INDISCERNIBLE] AND LINES REALLY 2923 02:12:12,520 --> 02:12:14,400 ARE SIGNIFICANTLY OVERLAPPING 2924 02:12:14,400 --> 02:12:16,160 AND THEREFORE HOW CAN WE 2925 02:12:16,160 --> 02:12:17,360 IDENTIFY HIGH RISK POPULATION 2926 02:12:17,360 --> 02:12:22,120 THAT WILL BENEFIT FROM POST CD19 2927 02:12:22,120 --> 02:12:23,880 CAR T-CELL TRANSPLANT AND WITHIN 2928 02:12:23,880 --> 02:12:26,200 OUR STUDY COHORT LOOKING AT 2929 02:12:26,200 --> 02:12:28,440 PATIENTS WITH HISTORY OF 2930 02:12:28,440 --> 02:12:29,960 TRANSPLANT REALIZE DIDN'T SEE 2931 02:12:29,960 --> 02:12:32,040 BENEFIT FOR PATIENTS TO FOLLOW 2932 02:12:32,040 --> 02:12:34,280 TRANCE PLANT FOLLOWING REMISSION 2933 02:12:34,280 --> 02:12:36,440 AND RED LINE PROCEEDED THOSE 2934 02:12:36,440 --> 02:12:38,080 WITH TRANSPLANT COMPARED TO 2935 02:12:38,080 --> 02:12:40,600 BLACK AND SURVIVAL NOT IMPROVED 2936 02:12:40,600 --> 02:12:44,240 AND IF PATIENTS HAD EARLY BCA 2937 02:12:44,240 --> 02:12:45,520 LOSS DEFINED AT DAY 63 THAT IS 2938 02:12:45,520 --> 02:12:48,200 WHERE YOU SEE REALLY NICE 2939 02:12:48,200 --> 02:12:50,160 IMPROVEMENT AND LEUKEMIA FREE 2940 02:12:50,160 --> 02:12:52,960 SURVIVAL THAT IS INCLUSIVE OF 2941 02:12:52,960 --> 02:12:55,120 PATIENTS WITH PRIOR TRANSPLANT 2942 02:12:55,120 --> 02:12:56,920 AND CHINA GROUP ALSO FURTHER 2943 02:12:56,920 --> 02:12:59,920 SUBDIVIDED PATIENTS AND ANALYZED 2944 02:12:59,920 --> 02:13:01,720 PATIENTS THAT ARE PARTICULARLY 2945 02:13:01,720 --> 02:13:03,440 HIGH RISK AND IDENTIFIED 2946 02:13:03,440 --> 02:13:05,040 PATIENTS THAT WERE HIGH DISEASE 2947 02:13:05,040 --> 02:13:07,480 BURDEN DEFINED GREATER THAN 5% 2948 02:13:07,480 --> 02:13:11,480 BONE MARROW AT TIME OF CAR 2949 02:13:11,480 --> 02:13:13,400 T-CELL INFLUGS AND FREE SURVIVAL 2950 02:13:13,400 --> 02:13:15,160 ON THE RIGHT AND OVERALL 2951 02:13:15,160 --> 02:13:16,240 SURVIVAL ON THE LEFT AND 2952 02:13:16,240 --> 02:13:17,880 SIGNIFICANT IMPROVEMENT AND 2953 02:13:17,880 --> 02:13:19,640 EVENT FOR SURVIVAL WITHIN THE 2954 02:13:19,640 --> 02:13:22,800 PATIENT COHORT AND THEY NOTED 2955 02:13:22,800 --> 02:13:24,960 BENEFIT WITH TRANSPLANT FOR 2956 02:13:24,960 --> 02:13:28,200 PATIENTS THAT HAVE POOR 2957 02:13:28,200 --> 02:13:30,320 PROGNOSTIC MARKERS WITHIN STUDY 2958 02:13:30,320 --> 02:13:34,320 DEFINED AT MLL AND ETAPDX1 AND 2959 02:13:34,320 --> 02:13:37,160 HERE, AGAIN, EVENT FREE SURVIVAL 2960 02:13:37,160 --> 02:13:39,480 SIGNIFICANTLY IMPROVED AND JUST 2961 02:13:39,480 --> 02:13:42,480 A TREND TOWARDS IMPROVEMENT OF 2962 02:13:42,480 --> 02:13:45,120 OVER ALL SURVIVAL AND REPORT OUT 2963 02:13:45,120 --> 02:13:47,640 OF THE HUTCH REPORTING ON ADULT 2964 02:13:47,640 --> 02:13:49,960 PATIENT POPULATION THAT RECEIVES 2965 02:13:49,960 --> 02:13:51,680 CD19 CAR AND PROCEEDED TO 2966 02:13:51,680 --> 02:13:53,840 TRANSPLANT REALLY HIGHLIGHTED 2967 02:13:53,840 --> 02:13:55,160 ALL WE WOULD EXPECT THERE IS 2968 02:13:55,160 --> 02:13:57,760 REALLY INCREASED MORTALITY RISK 2969 02:13:57,760 --> 02:13:59,280 ASSOCIATED WITH PATIENTS COMING 2970 02:13:59,280 --> 02:14:02,000 TO TRANSPLANT WITH HIGH 2971 02:14:02,000 --> 02:14:03,080 COMORBIDITY INDEX THAT 2972 02:14:03,080 --> 02:14:05,400 HIGHLIGHTS WE NEED TO DO A GOOD 2973 02:14:05,400 --> 02:14:07,600 JOB PICKING AND SELECTING 2974 02:14:07,600 --> 02:14:11,520 TRANSPLANT ELIGIBLE PATIENTS AND 2975 02:14:11,520 --> 02:14:13,480 THEN REPORTS OUT OF THE NIH 2976 02:14:13,480 --> 02:14:14,680 EXPERIENCE THIS IS A MULTITUDE 2977 02:14:14,680 --> 02:14:18,680 OF CARS WITH CD19 CARS AND 2978 02:14:18,680 --> 02:14:21,760 CD1922 AND CAR AND LOOKED AT 2979 02:14:21,760 --> 02:14:23,800 TRANSPLANT NAÏVE PATIENTS THOSE 2980 02:14:23,800 --> 02:14:26,200 PROCEEDING TRANSPLANT REMISSION 2981 02:14:26,200 --> 02:14:29,320 ATTAINMENT OVERALL DID WELL AND 2982 02:14:29,320 --> 02:14:33,440 THEY NOTED THAT PATIENTS WITH 2983 02:14:33,440 --> 02:14:35,960 OVER 5 LINES THERAPY PRIOR TO 2984 02:14:35,960 --> 02:14:37,840 IMMUNOTHERAPY DISEASE BURDEN HAD 2985 02:14:37,840 --> 02:14:39,680 TROUBLE AFTER RELAPSE AND 2986 02:14:39,680 --> 02:14:40,040 APOLOGIZE. 2987 02:14:40,040 --> 02:14:43,080 THAT IS A TYPO. ONE OF THE 2988 02:14:43,080 --> 02:14:45,320 EFFORTS WE ARE PROCEEDING 2989 02:14:45,320 --> 02:14:47,000 BECAUSE OF THE CAR CARE TRIAL 2990 02:14:47,000 --> 02:14:48,880 THAT MIKE MENTIONED IN 2991 02:14:48,880 --> 02:14:50,680 DISCUSSION OF THE CLONO SEEK AND 2992 02:14:50,680 --> 02:14:53,200 OBJECTIVE OF THIS TRIAL IS TO 2993 02:14:53,200 --> 02:14:55,600 ASSESS EFFICACY OF BIMARKER 2994 02:14:55,600 --> 02:14:57,200 GUIDED RISK BASED STRATEGY TO 2995 02:14:57,200 --> 02:14:59,600 MONTH N TORE REMISSION AND 2996 02:14:59,600 --> 02:15:01,160 SEQUENCING COLONO SEEK 2997 02:15:01,160 --> 02:15:02,680 MONITORING TO INFORM DECISION 2998 02:15:02,680 --> 02:15:05,960 MAKING FOR TRANSPLANTS AND WITH 2999 02:15:05,960 --> 02:15:07,960 THESE TRIAL AND WHAT THEY AIM TO 3000 02:15:07,960 --> 02:15:10,320 DO ENROLLING PATIENTS AROUND DAY 3001 02:15:10,320 --> 02:15:14,400 42 FOLLOWING CD19 CAR WITH 3002 02:15:14,400 --> 02:15:17,240 STIMULATORY DOMAIN WILL MONITOR 3003 02:15:17,240 --> 02:15:18,760 PATIENTS PERIPHERAL BLOOD EVERY 3004 02:15:18,760 --> 02:15:21,520 TWO WEEKS FOR B CELL APLASIA AND 3005 02:15:21,520 --> 02:15:24,400 CLONO SEEK MONITORING AND THEN 3006 02:15:24,400 --> 02:15:26,240 FREQUENT BONE MARROWS AT MONTH 3007 02:15:26,240 --> 02:15:29,760 2, 3, 6, 9 AND 12. WE ARE 3008 02:15:29,760 --> 02:15:34,440 HOPING TO IDENTIFY PATIENTS 3009 02:15:34,440 --> 02:15:36,960 PRIOR TO RELAPSE OR PATIENTS 3010 02:15:36,960 --> 02:15:40,040 REALLY HIGH RISK OF RELAPSING 3011 02:15:40,040 --> 02:15:41,920 RECOMMENDING TRANSPLANT DEFINED 3012 02:15:41,920 --> 02:15:44,800 IN B CELL RECOVERY IN 6 MONTHS 3013 02:15:44,800 --> 02:15:47,720 OR COLONO SEEK POSITIVITY AS 3014 02:15:47,720 --> 02:15:49,840 MIKE WAS DISCUSSING TOWARDS END 3015 02:15:49,840 --> 02:15:51,240 OF HIS PRESENTATION. 3016 02:15:51,240 --> 02:15:53,920 IT IS WITHIN 1 YEAR OF CAR 3017 02:15:53,920 --> 02:15:56,320 T-CELLS AND SECONDARY OBJECTIVES 3018 02:15:56,320 --> 02:15:59,920 TO DESCRIBE LEUKEMIA FREE 3019 02:15:59,920 --> 02:16:02,080 SURVIVAL AND RELAPSE WITHIN 3020 02:16:02,080 --> 02:16:03,280 PATIENT POPULATION AND 3021 02:16:03,280 --> 02:16:04,920 EXPLORATORY OBJECTIVES TO 3022 02:16:04,920 --> 02:16:07,560 EVALUATE RELATIONSHIP OF COLONO 3023 02:16:07,560 --> 02:16:09,280 SEEK TESTING IN BLOOD COMPARED 3024 02:16:09,280 --> 02:16:13,000 TO MARROW BLOOD COMPARED TO BONE 3025 02:16:13,000 --> 02:16:15,880 MARROW FLOW CITE OWE MTRY AND IN 3026 02:16:15,880 --> 02:16:17,960 BLOOD ELATING TO ABOUT. CELL 3027 02:16:17,960 --> 02:16:22,040 APLASIA AND WE ARE HOPING TO 3028 02:16:22,040 --> 02:16:24,560 EXPLORE T-CELL REPERTOIRE AND 3029 02:16:24,560 --> 02:16:29,080 DYNAMICS FOLLOWING CD19 T-CELL 3030 02:16:29,080 --> 02:16:31,480 AND PATIENTS AGES 1 THROUGH 25 3031 02:16:31,480 --> 02:16:38,320 YEARS AT TIME OF T-CELL CAR 3032 02:16:38,320 --> 02:16:40,360 TEEGS AND FLOW CITOMETRY AND 3033 02:16:40,360 --> 02:16:42,600 COLONO SEEK BY DAY 42 AND 3034 02:16:42,600 --> 02:16:44,160 EXPECTED TO HAVE ACCOUNT 3035 02:16:44,160 --> 02:16:46,560 RECOVERY ANC GREATER THAN 500 3036 02:16:46,560 --> 02:16:48,440 AND ABOUT. CELL APLASIA AND 3037 02:16:48,440 --> 02:16:51,320 NEED TO BE TRANSPLANT NAÏVE WITH 3038 02:16:51,320 --> 02:16:54,680 SUITABLE IDENTIFIED DONOR. 3039 02:16:54,680 --> 02:16:57,040 AND IN INCLUSION FROM MY VERY 3040 02:16:57,040 --> 02:17:00,280 SHORT TALK AND TRANSPLANT FOLLOW 3041 02:17:00,280 --> 02:17:10,800 ING CD19 CAR WITH 41B DOMAIN -- 3042 02:17:16,480 --> 02:17:19,920 THERE IS LIKELY A LOW RISK 3043 02:17:19,920 --> 02:17:23,120 POPULATION TO AVOID TRANSPLANT 3044 02:17:23,120 --> 02:17:25,440 WITHOUT COMPROMISING LEUKEMIA 3045 02:17:25,440 --> 02:17:30,720 SURVIVAL AND SAFELY AVOIDING 3046 02:17:30,720 --> 02:17:39,720 TRANSPLANT THAT MAY -- PRIOR 3047 02:17:39,720 --> 02:17:45,600 LINES OF THERAPY AND PATIENTS 3048 02:17:45,600 --> 02:17:47,240 HEAVILY PRE-TREATED IN THOSE WE 3049 02:17:47,240 --> 02:17:50,520 TRANLS PLANT AND AVOIDING 3050 02:17:50,520 --> 02:17:54,440 FEASIBILITY OF NEXT GEN 3051 02:17:54,440 --> 02:17:56,200 SEQUENCING HOPEFULLY WILL OFFER 3052 02:17:56,200 --> 02:17:57,680 IMPORTANT INSIGHTS. 3053 02:17:57,680 --> 02:18:03,160 I WOULD LIKE TO THANK SEATTLE 3054 02:18:03,160 --> 02:18:04,760 IMMUNOTHERAPY CREW AND PROTOCOL 3055 02:18:04,760 --> 02:18:06,440 DEVELOPMENT IS PATIENTS AND 3056 02:18:06,440 --> 02:18:09,400 FAMILIES AND THANKS FOR ALLOWING 3057 02:18:09,400 --> 02:18:14,920 ME TO SPEAK TO YOU TODAY. 3058 02:18:14,920 --> 02:18:23,240 NEXT IS -- CD19 RELAPSE 3059 02:18:23,240 --> 02:18:23,880 PREVEN 3060 02:18:23,880 --> 02:18:24,160 PREVENTION. 3061 02:18:24,160 --> 02:18:27,040 >> ALL RIGHT. I'M FROM SEATTLE 3062 02:18:27,040 --> 02:18:28,200 CHILDREN'S HOSPITAL AND I WILL 3063 02:18:28,200 --> 02:18:32,360 TALK ABOUT CD19 EXPRESSING TAPCS 3064 02:18:32,360 --> 02:18:35,680 BOOSTER STRATEGY FOLLOWING CD19 3065 02:18:35,680 --> 02:18:40,320 CAR T AND SORRY FOR FORMATTING 3066 02:18:40,320 --> 02:18:43,480 ISSUES CONVERSATION EARLIER 3067 02:18:43,480 --> 02:18:45,480 BETWEEN MIKE AND REGINA AND THIS 3068 02:18:45,480 --> 02:18:48,040 PROMPTED THAT AND ON STUDY PLAT 3069 02:18:48,040 --> 02:18:54,320 2 INVESTIGATION OF STRI CAR 3070 02:18:54,320 --> 02:18:56,440 1941BB CAR WE DID SHOW THAT WE 3071 02:18:56,440 --> 02:18:58,840 IDENTIFIED TWO RISK FACTORS FOR 3072 02:18:58,840 --> 02:19:01,200 PATIENTS EXPERIENCING EARLY LOSS 3073 02:19:01,200 --> 02:19:03,600 OF CAR T-CELL PERSISTENCE AND 3074 02:19:03,600 --> 02:19:08,560 FIRST IS ANTIGEN BONE MARROW 3075 02:19:08,560 --> 02:19:11,040 PRIOR TO DEPLETION. 3076 02:19:11,040 --> 02:19:14,480 BURDEN IN MARROW INCLUSIVE OF 3077 02:19:14,480 --> 02:19:16,640 MALIGNANT AND NONMALIGNANT B 3078 02:19:16,640 --> 02:19:19,000 CELLS AND INFERIOR DURATION IN 3079 02:19:19,000 --> 02:19:20,680 RED COMPARED TO B CELL DURATION 3080 02:19:20,680 --> 02:19:23,240 COMPARED TO THOSE WITH HIGHER 3081 02:19:23,240 --> 02:19:25,800 DISEASE OR ANTIGEN BURDEN AND 3082 02:19:25,800 --> 02:19:27,760 SECOND RISK FACTOR WE IDENTIFIED 3083 02:19:27,760 --> 02:19:29,960 IS EXPERIENCING RAPID EARLIER 3084 02:19:29,960 --> 02:19:32,040 CONTRACTION OF CARS FOLLOWING 3085 02:19:32,040 --> 02:19:34,720 INFLUGS APPEARED TO LOSE ABOUT. 3086 02:19:34,720 --> 02:19:39,960 CELL AMRASHIA EARLIER LOSS OF 3087 02:19:39,960 --> 02:19:42,240 PERSISTENCE DAY 10 AND 14 AFTER 3088 02:19:42,240 --> 02:19:44,280 CAR INFUSION CALCULATING A RATIO 3089 02:19:44,280 --> 02:19:46,520 AND PATIENTS WITH HIGH ERR 3090 02:19:46,520 --> 02:19:48,880 RATIOS EARLIER AND FASTER 3091 02:19:48,880 --> 02:19:50,320 CONTRACTIONS OF CAR T-CELL 3092 02:19:50,320 --> 02:19:51,880 NUMBERS AND IN BLUE YOU SEE 3093 02:19:51,880 --> 02:19:53,760 PATIENTS WITH HIGHER RATIOS AND 3094 02:19:53,760 --> 02:19:55,720 ARE PATIENTS THAT DIDN'T HAVE 3095 02:19:55,720 --> 02:19:58,640 PERSISTENCE OF CARS AT DAY 63 OR 3096 02:19:58,640 --> 02:20:01,720 ROUGHLY 2 MONTHS FOLLOWINGIN 3097 02:20:01,720 --> 02:20:03,240 FLUGS AND SETTING THRESHOLD OF 3098 02:20:03,240 --> 02:20:06,760 RATIO OF 1.5 AND HIGHER RATIO 3099 02:20:06,760 --> 02:20:08,480 PATIENTS RAPID EARLY CONTRACTORS 3100 02:20:08,480 --> 02:20:11,680 IN BLACK THEY HAVE FAR INFERIOR 3101 02:20:11,680 --> 02:20:13,240 PERSISTENCE COMPARED TO THOSE 3102 02:20:13,240 --> 02:20:15,320 THAT DIDN'T CONTRACT QUICKLY AND 3103 02:20:15,320 --> 02:20:17,960 WE SAID COMING TO HYPOTHESIZE IF 3104 02:20:17,960 --> 02:20:21,480 WE CAN FEED CARS IN VIVO POST 3105 02:20:21,480 --> 02:20:24,000 INFLUGS GIVING ANTIGEN 3106 02:20:24,000 --> 02:20:25,680 STIMULATION EXPANSION OF CARS IN 3107 02:20:25,680 --> 02:20:28,440 VIVO LEADING TO ENHANCED 3108 02:20:28,440 --> 02:20:30,520 PERSISTENCE AND DURABLE 3109 02:20:30,520 --> 02:20:32,520 REMISSIONS AND DOG THIS CREATED 3110 02:20:32,520 --> 02:20:37,080 NOVEL CELLULAR PRODUCT CD19 3111 02:20:37,080 --> 02:20:39,800 EXPRESSING ANTIGEN EXPRESSING 3112 02:20:39,800 --> 02:20:44,080 CELLS AND WE CLONED TRUNCATED 3113 02:20:44,080 --> 02:20:48,040 CD19 DESIGNATED BY T AND THIS 3114 02:20:48,040 --> 02:20:52,720 INCLUDED TRANS MEMBRANE AND WE 3115 02:20:52,720 --> 02:20:58,400 BASICALLY USED PATIENTS OT OL 3116 02:20:58,400 --> 02:21:00,120 GAUS T-CELLS TO TRANSDEUCE THIS 3117 02:21:00,120 --> 02:21:03,360 SHOWING UP TOP VECTOR DESIGNED 3118 02:21:03,360 --> 02:21:06,880 FOR CAR 19 AND WE HAVE IN 3119 02:21:06,880 --> 02:21:09,960 SEATTLE TAG FOR FLOW DETECTION 3120 02:21:09,960 --> 02:21:13,720 WITH -- TO TRANSLATE THIS WE 3121 02:21:13,720 --> 02:21:17,480 DEVELOP PLATTO 3 PILOT STUDY 3122 02:21:17,480 --> 02:21:19,480 FOLLOWING CAR 19 AND DIVIDED 3123 02:21:19,480 --> 02:21:22,240 INTO 2 PATIENT KOER HORTS AND 3124 02:21:22,240 --> 02:21:24,000 MANUFACTURING PLATFORMS ON THE 3125 02:21:24,000 --> 02:21:26,400 LEFT AND STARTING MATERIAL WE 3126 02:21:26,400 --> 02:21:30,040 USED WAS LEFTOVER AFORESIS 3127 02:21:30,040 --> 02:21:32,960 MATERIAL T-CELLS FROZEN DOWN 3128 02:21:32,960 --> 02:21:35,280 CRYOPRESERVE THE FORESIS FOR CAR 3129 02:21:35,280 --> 02:21:40,160 19 PRODUCTION AND THESE LOW 3130 02:21:40,160 --> 02:21:42,160 ANTIGEN PATIENTS IN DEPLETION 3131 02:21:42,160 --> 02:21:44,160 AND FOR PATIENTS THEY ARE 3132 02:21:44,160 --> 02:21:46,280 IDENTIFIED AT EARLY TIME POINT 3133 02:21:46,280 --> 02:21:48,520 AT WHICH POINT WE MANUFACTURER 3134 02:21:48,520 --> 02:21:51,160 TAPCS AND PATIENTS COULD BEGIN 3135 02:21:51,160 --> 02:21:56,520 DOSING OF TAPCS DAY 21 PROVIDED 3136 02:21:56,520 --> 02:21:58,440 CARS TOXICITY RESULTED AT THAT 3137 02:21:58,440 --> 02:22:01,160 TIME AND DOSING IS BELOW AND 3138 02:22:01,160 --> 02:22:03,160 PATIENT HAS 1 MILLION CAR CELLS 3139 02:22:03,160 --> 02:22:06,520 PER KILO AND THEY ARE DOSED 3140 02:22:06,520 --> 02:22:11,120 10 x 10 -- FLAT DOSE OF 5 x 10 3141 02:22:11,120 --> 02:22:12,760 CELLS FOR BIGGER PATIENTS THAT 3142 02:22:12,760 --> 02:22:15,960 CAN RECEIVE UP TO 6 DOSES OF 3143 02:22:15,960 --> 02:22:18,240 TAPCS EVERY FOUR WEEKS AND 3144 02:22:18,240 --> 02:22:20,680 PATIENTS DEMONSTRATE ONGOING 3145 02:22:20,680 --> 02:22:23,040 FUNCTIONAL PERSISTENCE OF 3146 02:22:23,040 --> 02:22:25,360 T-CELLS AND COHORT B INCLUDED 3147 02:22:25,360 --> 02:22:27,240 PATIENTS RAPID EARLIER 3148 02:22:27,240 --> 02:22:28,640 CONTRACTORS I PREVIOUSLY MENTION 3149 02:22:28,640 --> 02:22:31,240 THE AND OVERLAP BETWEEN TWO 3150 02:22:31,240 --> 02:22:33,600 PATIENT COHORTS THERE ARE 3151 02:22:33,600 --> 02:22:36,760 PATIENTS IN COHORT B WITH HIGH 3152 02:22:36,760 --> 02:22:37,960 ANTIGEN BURDEN AND CONTRACTION 3153 02:22:37,960 --> 02:22:39,920 OF T-CELLS AND FOR TIME I WON'T 3154 02:22:39,920 --> 02:22:42,280 GO INTO TOO MUCH WE ARE ABLE TO 3155 02:22:42,280 --> 02:22:44,600 CHARACTERIZE SOME EARLY SUBJECTS 3156 02:22:44,600 --> 02:22:47,560 CLINICAL TAPC PRODUCTS AND 3157 02:22:47,560 --> 02:22:48,760 SHOWING IN THE FIRST 7 SUBJECTS 3158 02:22:48,760 --> 02:22:51,920 OR SO OF THE FINAL TAPC PRODUCT 3159 02:22:51,920 --> 02:22:54,400 HOW MUCH WAS CD19 EXPRESSING AND 3160 02:22:54,400 --> 02:22:56,840 BLUE AND GREEN ARE BREAKDOWN OF 3161 02:22:56,840 --> 02:22:59,160 CD48 AND PRODUCTS WE DIDN'T 3162 02:22:59,160 --> 02:23:02,320 CONTROL FOR AND IDEA BEHIND THIS 3163 02:23:02,320 --> 02:23:05,920 IS MIMICKING WHAT MARROW OR B 3164 02:23:05,920 --> 02:23:07,560 CELLS IN PERIPHERAL BLOOD COULD 3165 02:23:07,560 --> 02:23:10,040 STIMULATE CARS AND LOOKING TO 3166 02:23:10,040 --> 02:23:14,280 SEE FOR EXAMPLE HOW TAPCS 3167 02:23:14,280 --> 02:23:16,000 COMPARE AND ANTIGEN BINDING 3168 02:23:16,000 --> 02:23:17,920 CAPACITY AND PRODUCTS IN PURPLE 3169 02:23:17,920 --> 02:23:22,160 THAT ARE COMPARED TO O AND 3170 02:23:22,160 --> 02:23:24,120 PERIPHERAL BLOOD SAMPLES AND 3171 02:23:24,120 --> 02:23:27,520 T-CELL INFLUGS AND TAPCS LOOKED 3172 02:23:27,520 --> 02:23:29,800 SIMILAR TO BONE MARROW FOR 3173 02:23:29,800 --> 02:23:32,360 EXAMPLE AND CD19 EXPRESSION IN 3174 02:23:32,360 --> 02:23:33,920 BINDING CAPACITY COMPARED TO THE 3175 02:23:33,920 --> 02:23:36,040 BLOOD AND LOOKED TO SEE HOW 3176 02:23:36,040 --> 02:23:37,120 THESE COMPARE TO BLOOD AND 3177 02:23:37,120 --> 02:23:39,880 MARROW IN TERMS OF COSTIMULATORY 3178 02:23:39,880 --> 02:23:41,720 MARKER IN EXPRESSION AND OVERALL 3179 02:23:41,720 --> 02:23:44,680 IN PURPLE OR TAPCS MARROW IS 3180 02:23:44,680 --> 02:23:47,240 GREEN AND BLOOD IS BLUE AND YOU 3181 02:23:47,240 --> 02:23:50,920 SEE FOR EXAMPLE CD54ICAM1 AND 3182 02:23:50,920 --> 02:23:55,120 LESS PROPORTION OF IT TAPCS 3183 02:23:55,120 --> 02:23:58,120 EXPRESS THIS WITH OVERALL HIGH 3184 02:23:58,120 --> 02:24:02,920 FMI AND CD80 AND CD6 EXPRESSION 3185 02:24:02,920 --> 02:24:05,600 THAT IS ENDOGENOUS ANTIGEN 3186 02:24:05,600 --> 02:24:08,280 PRESENTING CELL MARKER ON B 3187 02:24:08,280 --> 02:24:10,240 CELLS AND DENDRITIC CELLS NOT 3188 02:24:10,240 --> 02:24:12,080 EXPECT TODAY BE ON T-CELLS AND 3189 02:24:12,080 --> 02:24:13,840 OVERALL NOT LOOKING ACROSS 3190 02:24:13,840 --> 02:24:17,080 MARKERS I WILL SAY THAT TAPC 3191 02:24:17,080 --> 02:24:19,600 PRODUCTS IN BOTTOM ROW HAVE FAIR 3192 02:24:19,600 --> 02:24:21,480 NUMBER OF COSTIMULATORY MARKERS 3193 02:24:21,480 --> 02:24:23,880 COMPARED TO BLOOD AND MARROW AND 3194 02:24:23,880 --> 02:24:30,800 INCUBATED PATIENTS TACP PRODUCTS 3195 02:24:30,800 --> 02:24:35,200 BONE MARROW IS ONE-TO-ONE TARGET 3196 02:24:35,200 --> 02:24:39,080 2 EFFECTOR RATIO FOR BONE MARROW 3197 02:24:39,080 --> 02:24:42,880 CD19 EXPRESSING CELLS AND TAPCS 3198 02:24:42,880 --> 02:24:47,120 YOU SEE OVERALL THESE PRODUCTS 3199 02:24:47,120 --> 02:24:48,840 PRODUCED FAIR AMOUNT OF 3200 02:24:48,840 --> 02:24:52,800 PRODUCTION WITH CAR PRODUCTS AND 3201 02:24:52,800 --> 02:24:58,920 OVERALL FOR THE TRIAL, WE HAD 3202 02:24:58,920 --> 02:24:59,600 SUCCESSFUL CLINICAL EXPERIENCE 3203 02:24:59,600 --> 02:25:02,120 TO DATE AND CELLS WERE 3204 02:25:02,120 --> 02:25:03,120 MANUFACTURED IN ONE DOSE FOR 3205 02:25:03,120 --> 02:25:04,960 MAJORITY OF PATIENTS WITH 3206 02:25:04,960 --> 02:25:07,600 AVERAGE OF 5 DOSES PRODUCED PER 3207 02:25:07,600 --> 02:25:11,040 PATIENT AND ONE PATIENT LOST 3208 02:25:11,040 --> 02:25:13,720 PERSISTENCE OF CAR T-CELLS PRIOR 3209 02:25:13,720 --> 02:25:17,440 TO DOSING NOT ELIGIBLE TO GET 3210 02:25:17,440 --> 02:25:20,840 TAPCS AND PRODUCT FOR 3211 02:25:20,840 --> 02:25:22,160 CONTAMINATION AND SO ALL 3212 02:25:22,160 --> 02:25:24,480 TOGETHER WE TREATED 7 3213 02:25:24,480 --> 02:25:26,160 TAENSUBJECTS WITH 1 DOSE OF 3214 02:25:26,160 --> 02:25:28,480 TAPCS AND HAVE BEEN TOLERATED 3215 02:25:28,480 --> 02:25:32,160 EXTREMELY WELL AND ONE TOXICITY 3216 02:25:32,160 --> 02:25:34,000 GRANT GRADE 3 REACTION AFTER 3217 02:25:34,000 --> 02:25:37,640 SUBJECT SECOND TAPC DOSE THAT 3218 02:25:37,640 --> 02:25:40,560 PRECLUDED FURTHER TAPC DOSING AT 3219 02:25:40,560 --> 02:25:42,680 THAT POINT IN TIME NEUROTOXICITY 3220 02:25:42,680 --> 02:25:45,200 AND SO FAR RIGHT NOW WE HAVE 3221 02:25:45,200 --> 02:25:47,880 SUBJECTS THAT COMPLETED APC 3222 02:25:47,880 --> 02:25:48,200 INFUSIONS. 3223 02:25:48,200 --> 02:25:50,040 SO, JUST TO WALK THROUGH A 3224 02:25:50,040 --> 02:25:51,520 COUPLE PATIENT EXPERIENCES THIS 3225 02:25:51,520 --> 02:25:53,840 IS ONE PATIENT'S TIME COURSE AND 3226 02:25:53,840 --> 02:25:56,600 TO ORIENT YOU OPEN TRIANGLE IS 3227 02:25:56,600 --> 02:25:59,120 CAR INFUSION IN EACH OF THE 3228 02:25:59,120 --> 02:26:01,320 CLOSED TRIANGLES ARE TAPC 3229 02:26:01,320 --> 02:26:03,240 INFUSION OVER TIME AND IN BLUE 3230 02:26:03,240 --> 02:26:05,720 IS POSITIVE CAR T-CELLS 3231 02:26:05,720 --> 02:26:08,320 DETECTING THROUGH TAG AND CD3 3232 02:26:08,320 --> 02:26:10,800 COEXPRESSION AND IN GREEN ARE 3233 02:26:10,800 --> 02:26:14,720 TAPCS IDENTIFYING BY FLOWS 3234 02:26:14,720 --> 02:26:18,280 EXPRESSING -- AFTER PATIENTS 3235 02:26:18,280 --> 02:26:19,840 INITIAL CAR T-CELL EXPANSION 3236 02:26:19,840 --> 02:26:22,720 COMMENCING WITH TAPCS AND SEEING 3237 02:26:22,720 --> 02:26:24,720 NOT AFTER EVERY DOSE BUT SEVERAL 3238 02:26:24,720 --> 02:26:27,960 DOSES OF TAPCS REEXPANSION OF 3239 02:26:27,960 --> 02:26:31,240 CAR POSITIVE CELLS AND THEY ARE 3240 02:26:31,240 --> 02:26:32,960 TRANSIENTLY DETECTED AND ARE 3241 02:26:32,960 --> 02:26:35,080 ELIMINATE THE QUICKLY AS YOU 3242 02:26:35,080 --> 02:26:38,520 EXPECT WITH ONGOING FUNCTIONAL 3243 02:26:38,520 --> 02:26:42,400 CAR T PERSISTENCE AND APLASIA IS 3244 02:26:42,400 --> 02:26:44,760 IN ORANGE AND NOTABLE DETECTIBLE 3245 02:26:44,760 --> 02:26:46,600 CELLS THROUGHOUT THE COURSE IS 3246 02:26:46,600 --> 02:26:47,760 ANOTHER SUBJECT THAT IS SHOWING 3247 02:26:47,760 --> 02:26:49,480 THAT AFTER THEY COMPLETED THEIR 3248 02:26:49,480 --> 02:26:50,920 COURSE THIS PATIENT WENT ON TO 3249 02:26:50,920 --> 02:26:52,840 HAVE RECOVERY OF ABOUT. CELLS 3250 02:26:52,840 --> 02:26:55,040 THAT IS INTERESTING AND NOT TOO 3251 02:26:55,040 --> 02:26:57,200 LONG AFTER ABOUT A MONTH AFTER 3252 02:26:57,200 --> 02:27:01,440 LAST TAPC DOSE THAT WOULD HAVE 3253 02:27:01,440 --> 02:27:02,680 BEEN DUE FOR ANOTHER DOSE TO 3254 02:27:02,680 --> 02:27:04,680 HAVE THEM AND INTERESTING TO SEE 3255 02:27:04,680 --> 02:27:06,720 THAT RECOVERY AND WITH IT THAT 3256 02:27:06,720 --> 02:27:08,920 DID NOT HAVE SUBSEQUENT 3257 02:27:08,920 --> 02:27:10,600 REEXPANSION OF CELLS NOT 3258 02:27:10,600 --> 02:27:12,960 TRIGGERED BY B CELLS AND YOU CAN 3259 02:27:12,960 --> 02:27:14,960 SEE NUMBER UP THERE. 3260 02:27:14,960 --> 02:27:15,880 ESSENTIALLY ONE INTERESTING 3261 02:27:15,880 --> 02:27:19,240 THING WE SAW IS 3 OF 17 TREATED 3262 02:27:19,240 --> 02:27:22,600 SUBJECTS HAD HIGHEST DETECTIBLE 3263 02:27:22,600 --> 02:27:25,400 EFGR CAR NOTE NUMBER FOLLOWING 3264 02:27:25,400 --> 02:27:27,600 TAPC DOSE RATHER THAN INITIAL 3265 02:27:27,600 --> 02:27:28,560 EXPANSION AFTER CARS. 3266 02:27:28,560 --> 02:27:31,360 THIS IS A COHORT A SUBJECT AND 3267 02:27:31,360 --> 02:27:33,400 HAD LOW ANTIGEN BURDEN THAT SORT 3268 02:27:33,400 --> 02:27:36,480 OF REFLECTS THAT DIMINISH RED 3269 02:27:36,480 --> 02:27:38,240 EXPANSION WE SOMETIMES SEE 3270 02:27:38,240 --> 02:27:42,720 FOLLOWING CARS WITH LOW ANTIGEN 3271 02:27:42,720 --> 02:27:43,240 BURDEN. 3272 02:27:43,240 --> 02:27:45,280 ANOTHER INTERESTING PHENOMENON 3273 02:27:45,280 --> 02:27:48,840 AFTER A COUPLE PATIENTS AFTER 3274 02:27:48,840 --> 02:27:51,320 TAPC DOSE LOST CAR T-CELL 3275 02:27:51,320 --> 02:27:53,480 PERSISTENCE RECOVERY B CELLS IN 3276 02:27:53,480 --> 02:27:55,360 ORANGE IN BOTH PATIENTS IN 3277 02:27:55,360 --> 02:27:57,600 SETTING WE SAW PROLIFERATION OF 3278 02:27:57,600 --> 02:28:00,640 TAPCS AS WELL NO LONGER 3279 02:28:00,640 --> 02:28:03,000 FUNCTIONAL CAR T-CELL 3280 02:28:03,000 --> 02:28:05,080 PERSISTENCE TO ELIMINATE CELLS 3281 02:28:05,080 --> 02:28:06,840 AND SHORT OF GRAPHS HERE 3282 02:28:06,840 --> 02:28:08,920 PATIENTS WENT ON TO RECEIVE 3283 02:28:08,920 --> 02:28:10,400 ADDITIONAL DIRECTED THERAPY FOR 3284 02:28:10,400 --> 02:28:11,920 TRANSPLANT 1 OR ADDITIONAL 3285 02:28:11,920 --> 02:28:13,720 THERAPY AFTER RELAPSE 1 FOR A 3286 02:28:13,720 --> 02:28:17,800 SEBLGD AND FOLLOWED IN TPCS WE 3287 02:28:17,800 --> 02:28:19,640 WERE ELIMINATED BUT INTERESTING 3288 02:28:19,640 --> 02:28:23,240 PHENOMENON TO SEE THEM 3289 02:28:23,240 --> 02:28:29,400 PROLIFERATING IN VIVO TOO THIS 3290 02:28:29,400 --> 02:28:30,240 IS PRELIMINARY. 3291 02:28:30,240 --> 02:28:32,600 LOOKING ACROSS PATIENTS FOR 3292 02:28:32,600 --> 02:28:35,240 ESSENTIALLY B CELL RECOVERY ON 3293 02:28:35,240 --> 02:28:39,080 THE RIGHT LOOKING AT HIGH LEVEL 3294 02:28:39,080 --> 02:28:40,280 VIEW NOT ALL THAT DIFFERENCE AND 3295 02:28:40,280 --> 02:28:43,720 GOES OUT TO 2 YEARS FOR PATIENTS 3296 02:28:43,720 --> 02:28:47,000 BETTER FOR WHAT WE REPORTED FOR 3297 02:28:47,000 --> 02:28:50,320 CAR 19 ALONE AND I WILL SEE 3298 02:28:50,320 --> 02:28:52,320 PATTERN RELAPSE THAT IS 3299 02:28:52,320 --> 02:28:55,280 INTERESTING SEVERAL PATIENTS 3300 02:28:55,280 --> 02:28:58,440 ONGOING B CELL APLASIA AND CD19 3301 02:28:58,440 --> 02:28:59,680 POSITIVE RELAPSE AND INTERESTING 3302 02:28:59,680 --> 02:29:02,320 TO HEAR IT AND WHAT OTHERS 3303 02:29:02,320 --> 02:29:04,400 EXPERIENCED WITH US AS WELL AND 3304 02:29:04,400 --> 02:29:08,040 PATIENTS BEYOND THIS DATA MORE 3305 02:29:08,040 --> 02:29:09,760 RECENTLY THAT RELAPSED LATER 3306 02:29:09,760 --> 02:29:13,280 THAN WHAT PATIENTS HAD WITH CD19 3307 02:29:13,280 --> 02:29:14,680 POSITIVE DISEASE AND PUSHING 3308 02:29:14,680 --> 02:29:18,080 BACK TIMING OF CD19 POSITIVE 3309 02:29:18,080 --> 02:29:21,040 RELAPSE AND NOTHING TO PROHIBIT 3310 02:29:21,040 --> 02:29:23,160 ANTIGEN ESCAPE AND SEVERAL 3311 02:29:23,160 --> 02:29:27,960 PATIENTS SEEING CD19 -- LINEAGE 3312 02:29:27,960 --> 02:29:29,880 SWITCH WITH ARRANGEMENT. 3313 02:29:29,880 --> 02:29:32,480 SO, NEXT STEPS FOR TAPCS I THINK 3314 02:29:32,480 --> 02:29:34,640 STILL A LITTLE UNCLEAR COLLATING 3315 02:29:34,640 --> 02:29:37,520 DATA AND COMPLETING IT WE HAVE 3316 02:29:37,520 --> 02:29:41,400 SHOWN HAVE BEEN SUCCESSFULLY 3317 02:29:41,400 --> 02:29:45,080 MANUFACTURED STORING -- WITHOUT 3318 02:29:45,080 --> 02:29:46,040 SIGNIFICANT TOXICITY. 3319 02:29:46,040 --> 02:29:49,560 IT IS INTERESTING TO SEE EP 3320 02:29:49,560 --> 02:29:52,360 SOTIC REEXPANSIONS THEY PRODUCE 3321 02:29:52,360 --> 02:29:55,000 IN VIVO IN CD19 CARS AND THINK 3322 02:29:55,000 --> 02:29:56,440 IN TERMS WHETHER THIS WILL 3323 02:29:56,440 --> 02:29:57,760 TRANSLATE INTO DURABLE REMISSION 3324 02:29:57,760 --> 02:30:00,720 AND PREVENTION OF CD19 POSITIVE 3325 02:30:00,720 --> 02:30:03,240 RELAPSE IS UNKNOWN AND 3326 02:30:03,240 --> 02:30:07,320 RANDOMIZING PATIENTS TO TAPCS OR 3327 02:30:07,320 --> 02:30:11,200 NOT TO ANSWER THIS QUESTION. 3328 02:30:11,200 --> 02:30:13,000 I WILL STOP THERE THANKING 3329 02:30:13,000 --> 02:30:15,160 SEATTLE TEAM AS WELL AND THANKS 3330 02:30:15,160 --> 02:30:17,040 TO ORGANIZERS AND PLANNING 3331 02:30:17,040 --> 02:30:20,200 COMMITTEE FOR HAVING ME TALK 3332 02:30:20,200 --> 02:30:30,520 ABOUT THIS TODAY. 3333 02:30:32,000 --> 02:30:35,200 >> TO THE NEXT SPEAKERS. 3334 02:30:35,200 --> 02:30:41,040 >> THANK YOU. THANK YOU TO 3335 02:30:41,040 --> 02:30:43,760 NIRALI AND ORGANIZERS FOR 3336 02:30:43,760 --> 02:30:48,600 INVITING ME FOR DIFFICULT 3337 02:30:48,600 --> 02:30:48,840 SUBJECTS. 3338 02:30:48,840 --> 02:30:59,320 THIS MAYBE WORKS. 3339 02:31:13,520 --> 02:31:16,400 >> I MUST EMPHASIZE HERE FREAK 3340 02:31:16,400 --> 02:31:18,200 WEDNESDAY OF MONITORING AND 3341 02:31:18,200 --> 02:31:22,480 DEFINITION OF APLASIA AND 3342 02:31:22,480 --> 02:31:23,000 PERIPHERAL BLOOD IS NOT 3343 02:31:23,000 --> 02:31:24,440 CONSENSUAL AT THE MOMENT AND 3344 02:31:24,440 --> 02:31:26,880 COULD BE COLLABORATION ITEM FOR 3345 02:31:26,880 --> 02:31:29,680 THIS GROUP AND SECOND POINT IS 3346 02:31:29,680 --> 02:31:33,640 MAYBE IT IS MORE INTERESTING TO 3347 02:31:33,640 --> 02:31:38,320 DETECT EARLIER BONE MARROW 3348 02:31:38,320 --> 02:31:39,920 RECOVERY AND SHOWN IN 3349 02:31:39,920 --> 02:31:42,280 [INDISCERNIBLE] 2021 AND SECOND 3350 02:31:42,280 --> 02:31:44,160 POSSIBILITIES REINFUSION FOR 3351 02:31:44,160 --> 02:31:47,240 NONRESPONSE OR RELAPSE WHATEVER 3352 02:31:47,240 --> 02:31:50,280 YOU DEFINE RELAPSE BY POSITIVITY 3353 02:31:50,280 --> 02:31:54,160 AND MORPHOLOGY AND QUESTION IS 3354 02:31:54,160 --> 02:32:00,480 IS CD19 POSITIVE OR NEGATIVE AND 3355 02:32:00,480 --> 02:32:04,080 PRODUCT ACCORDING TO 3356 02:32:04,080 --> 02:32:05,400 CHARACTERISTIC IS OF UTMOST 3357 02:32:05,400 --> 02:32:09,040 IMPORTANCE AND CD19 POSITIVE 3358 02:32:09,040 --> 02:32:10,680 SECOND INFUSION COULD BE OF SAME 3359 02:32:10,680 --> 02:32:13,920 PRODUCT IF YOU HAVE REMAINING 3360 02:32:13,920 --> 02:32:16,040 CELLS AND QUESTIONING OF DOSE 3361 02:32:16,040 --> 02:32:18,120 THAT WE HAVE SPOKEN THIS MORNING 3362 02:32:18,120 --> 02:32:20,440 AND COULD ALSO THINK BRILLIANTLY 3363 02:32:20,440 --> 02:32:22,960 SHOWN BY SHANNON DIFFERENT CAR 3364 02:32:22,960 --> 02:32:26,400 FOR EXAMPLE HUMANIZED 1 AND CD19 3365 02:32:26,400 --> 02:32:29,520 NEGATIVE YOU HAVE TO THINK NOT 3366 02:32:29,520 --> 02:32:31,680 ABOUT REINFUSION BUT INFUSION OF 3367 02:32:31,680 --> 02:32:34,440 TOTALLY DIFFERENT CAR TARGETING 3368 02:32:34,440 --> 02:32:37,200 ANOTHER ANCONTINUALEN AND OF 3369 02:32:37,200 --> 02:32:41,080 NOTE IN REAL WORLD DATA SHOWN BY 3370 02:32:41,080 --> 02:32:44,720 US IN URA CD19 RELAPSE 3371 02:32:44,720 --> 02:32:46,360 PROPORTION IS 50 TO 60% THAT IS 3372 02:32:46,360 --> 02:32:53,600 ONLY 15% IN THE ILIANA TRIAL AND 3373 02:32:53,600 --> 02:32:57,200 IN THIS CONTEXT CHOICE PROBLEM 3374 02:32:57,200 --> 02:33:01,800 IS DO YOU HAVE AVAILABLE OF 3375 02:33:01,800 --> 02:33:07,240 ALTERNATIVE CAR T SHOWN BY ELAD 3376 02:33:07,240 --> 02:33:08,880 DIFFERENT TRIALS IN THE WORLD 3377 02:33:08,880 --> 02:33:11,960 ARE EXTREMELY SPARSED AND 3378 02:33:11,960 --> 02:33:15,880 PREVIOUS EXPANSION IS PARAMETER. 3379 02:33:15,880 --> 02:33:19,720 REMAINING PRODUCT AND I QUOTED 3380 02:33:19,720 --> 02:33:26,200 THIS SENTENCE FROM BLOOD THAT 3381 02:33:26,200 --> 02:33:32,800 DOSE INCREASE PRAR EFFECTS OF 3382 02:33:32,800 --> 02:33:33,840 ANTI-CAR IMMUNE RESPONSE AND 3383 02:33:33,840 --> 02:33:37,240 TREND THAT IS INCREASING IN THE 3384 02:33:37,240 --> 02:33:39,640 WORLD IS IF CAR T1 HAVE BEEN 3385 02:33:39,640 --> 02:33:41,280 DONE FOR RELAPSE POST TRANSPLANT 3386 02:33:41,280 --> 02:33:44,920 CAN WE THINK ABOUT THE 3387 02:33:44,920 --> 02:33:47,000 AVAILABILITY OF DONOR DERIVED 3388 02:33:47,000 --> 02:33:50,520 T-CELLS IT THAT COULD BE FITTER, 3389 02:33:50,520 --> 02:33:52,520 OBVIOUSLY. ANOTHER ITEM IS 3390 02:33:52,520 --> 02:33:55,160 DEPLETION AND NO LYMPHO 3391 02:33:55,160 --> 02:33:56,560 DEPLETION PRIOR TO REINFUSIONS 3392 02:33:56,560 --> 02:33:59,080 TO BE AVOIDED AND SAME WITH 3393 02:33:59,080 --> 02:34:00,800 DEPLETION THAT IS GENERALLY 3394 02:34:00,800 --> 02:34:03,520 CHOOSING OR INTENSIFIED FOR 3395 02:34:03,520 --> 02:34:04,800 DEPLETION BECAUSE PREVIOUS 3396 02:34:04,800 --> 02:34:08,160 EXPANSION IF VERY LOW FOR 3397 02:34:08,160 --> 02:34:10,480 EXAMPLE OUR RESPONSE COULD BE 3398 02:34:10,480 --> 02:34:13,840 PARAMETERS OF CHOICE TO DECIDE 3399 02:34:13,840 --> 02:34:16,880 TO INCREASE LYMPHO DEPLETION AND 3400 02:34:16,880 --> 02:34:19,440 SHOWN BY NIRALI IN 3401 02:34:19,440 --> 02:34:22,120 [INDISCERNIBLE] AND SHOWN ALSO 3402 02:34:22,120 --> 02:34:24,120 THIS MORNING MODELING OF 3403 02:34:24,120 --> 02:34:26,160 PREVIOUS FLU EXPOSURE COULD BE 3404 02:34:26,160 --> 02:34:30,000 WAY TO SAY LET'S INCREASE DOSE 3405 02:34:30,000 --> 02:34:34,480 OF FLU TO MAYBE HAVE ADEQUATE 3406 02:34:34,480 --> 02:34:37,560 EXPOSURE TO FLU FOR BETTER 3407 02:34:37,560 --> 02:34:38,200 EXPANSION. 3408 02:34:38,200 --> 02:34:40,240 DATA AND EARLIER EXPERIENCES 3409 02:34:40,240 --> 02:34:43,240 WITH REINFUSION SHOWN BY SHANNON 3410 02:34:43,240 --> 02:34:47,880 IN DUBLIN IN 2016 AND SHANNON 3411 02:34:47,880 --> 02:34:50,440 PROBABLY REMIND THIS THIS IS OLD 3412 02:34:50,440 --> 02:34:54,680 THING NOW AND HAS BEEN UPDATED 3413 02:34:54,680 --> 02:34:56,200 ASH 2021 BY [INDISCERNIBLE] AND 3414 02:34:56,200 --> 02:35:00,360 I WILL TALK ABOUT DATA A LITTLE 3415 02:35:00,360 --> 02:35:01,880 AFTER. 3416 02:35:01,880 --> 02:35:04,320 REBECCA PUBLISHED IN BLOOD 3417 02:35:04,320 --> 02:35:06,760 SEATTLE EXPERIENCE IN 10 3418 02:35:06,760 --> 02:35:10,320 PATIENTS LOSS OF MRASHIA 8 3419 02:35:10,320 --> 02:35:13,680 INFUSED AND 2 OUT OF THEM HAVE 3420 02:35:13,680 --> 02:35:15,440 REENGRAPHMENT AND INTERESTINGLY 3421 02:35:15,440 --> 02:35:19,840 6 OF 8 HAD NO FLU BEFORE CAR T1 3422 02:35:19,840 --> 02:35:23,560 AND RELAPSE OUT OF TWO PATIENTS 3423 02:35:23,560 --> 02:35:25,080 ONE HAD [INDISCERNIBLE] AND VERY 3424 02:35:25,080 --> 02:35:30,360 SMALL NUMBERS THAT ARE DIFFICULT 3425 02:35:30,360 --> 02:35:31,800 TO EXTRACT SOMETHING. 3426 02:35:31,800 --> 02:35:34,240 REGINA, THANK YOU TO ALLOW ME TO 3427 02:35:34,240 --> 02:35:36,560 SHOW 2 OF THREE SLIDES FOR 3428 02:35:36,560 --> 02:35:38,760 PRESENTATION AT ASH. WE CAN 3429 02:35:38,760 --> 02:35:41,400 CONCLUDE C AND FIRST IN TERMS OF 3430 02:35:41,400 --> 02:35:45,120 RELAPSE PREVENTION AND 3431 02:35:45,120 --> 02:35:46,800 REINSTALLATION OF B CELL 3432 02:35:46,800 --> 02:35:49,840 APLASIA. IF YOU DO LYMPHO 3433 02:35:49,840 --> 02:35:51,120 DEPLETING CHEMOTHERAPY 3434 02:35:51,120 --> 02:35:53,440 APPROXIMATELY HALF OF PATIENT OR 3435 02:35:53,440 --> 02:35:55,600 48% AND DOING IT AT 3436 02:35:55,600 --> 02:35:57,360 [INDISCERNIBLE] LEVEL AND BONE 3437 02:35:57,360 --> 02:36:01,600 MARROW RECOVERY IS 76%. 3438 02:36:01,600 --> 02:36:05,320 SO, MAYBE ACTING EARLIER IS 3439 02:36:05,320 --> 02:36:15,400 BETTER DOING RELAPSE RATE OF 3440 02:36:15,400 --> 02:36:17,800 THIS IS 50% APPROXIMATELY AND IF 3441 02:36:17,800 --> 02:36:22,040 DOING FOR NONINITIAL RESPONSE 3442 02:36:22,040 --> 02:36:32,520 RATE OF RESPONSE IS 0 IF YOU DO 3443 02:36:32,520 --> 02:36:35,520 REINFUSION FOR CAR T-CELL 3444 02:36:35,520 --> 02:36:42,120 PREVENTION YOU HAVE OBSERVE THE 3445 02:36:42,120 --> 02:36:44,080 NOTHING AND FOR RELAPSE YOU HAVE 3446 02:36:44,080 --> 02:36:47,240 CMS AND THIS PAPER IS FIRST 3447 02:36:47,240 --> 02:36:49,000 REINFUSION ARE SAFE AND SECOND 3448 02:36:49,000 --> 02:36:52,480 THERE MIGHT BE B CELL APLASIA 3449 02:36:52,480 --> 02:36:55,240 AND SHORT CAR T PERSISTENCE AND 3450 02:36:55,240 --> 02:36:59,240 PASHGIENTS WITH CD19 POSITIVE 3451 02:36:59,240 --> 02:37:03,280 NOT EFFECTIVE FOR NONRESPONSE 3452 02:37:03,280 --> 02:37:05,680 AND PROPOSAL OF GROUP IS 3453 02:37:05,680 --> 02:37:07,920 OFFERING REINFUSION FOR BCR 3454 02:37:07,920 --> 02:37:08,520 RECOVERY IN [INDISCERNIBLE] 3455 02:37:08,520 --> 02:37:12,560 WITHIN 6 MONTHS OF INITIAL 3456 02:37:12,560 --> 02:37:17,160 INFUSION AND PRWCC HAVE SHOWN 3457 02:37:17,160 --> 02:37:20,800 THIS AND 57 PATIENTS RELAPSE 3458 02:37:20,800 --> 02:37:23,240 AFTER T-CELL AND UNFORTUNATELY 3459 02:37:23,240 --> 02:37:27,000 ONLY 10 PATIENTS RECEIVED CAR T 3460 02:37:27,000 --> 02:37:28,640 THERAPY AND OUT OF THIS I FOUND 3461 02:37:28,640 --> 02:37:33,240 ONLY 5 THAT RECEIVED REINFUSION 3462 02:37:33,240 --> 02:37:35,200 OF T-CELL GLUCOCELL AND IN TERMS 3463 02:37:35,200 --> 02:37:38,040 OF RESPONSE OF RELAPSE THREE OF 3464 02:37:38,040 --> 02:37:40,040 THE FIVE ARE REINFUSION AND 3 3465 02:37:40,040 --> 02:37:44,920 OUT OF 3 FOR HUMANIZED CD19 CAR 3466 02:37:44,920 --> 02:37:47,560 AND ONE FOR COMBINATION OF 3467 02:37:47,560 --> 02:37:52,560 INFUSION PLUS VOLUME AND PLUS 3468 02:37:52,560 --> 02:37:52,960 [INDISCERNIBLE]. 3469 02:37:52,960 --> 02:37:56,760 GROUP OF NIRALI PUBLISHED ALSO 3470 02:37:56,760 --> 02:38:02,120 IS EXPERIENCE AND UNFORTUNATELY 3471 02:38:02,120 --> 02:38:03,640 HERE AGAIN NUMBER ARE SMALL AND 3472 02:38:03,640 --> 02:38:07,080 7 PATIENTS HAVE CR AND P. ARE. 3473 02:38:07,080 --> 02:38:11,080 AT CAR 2 AND RESPONSE IS ONLY 3474 02:38:11,080 --> 02:38:14,840 38% COMPARED TO 72% AFTER CAR 3475 02:38:14,840 --> 02:38:17,360 T1. AFTER YOU LOOK AT DOWNSIDE 3476 02:38:17,360 --> 02:38:19,360 OF THE PANEL AND DATA IN TERMS 3477 02:38:19,360 --> 02:38:23,240 OF LONG-TERM THAT HAVE COME FOR 3478 02:38:23,240 --> 02:38:26,720 PATIENT BROUGHT TO CR BY SECOND 3479 02:38:26,720 --> 02:38:30,600 INFUSION OF CAR T IS RED THAT I 3480 02:38:30,600 --> 02:38:33,280 PUT AND ALL PATIENT DIE 3481 02:38:33,280 --> 02:38:35,120 ESSENTIALLY AND EXPERIENCE HAS 3482 02:38:35,120 --> 02:38:39,440 BEEN MORE THAN DISAPPOINTING FOR 3483 02:38:39,440 --> 02:38:43,000 EARLY LOSS OF BC APLASIA AND 3484 02:38:43,000 --> 02:38:45,160 EXPANSE PATIENTS 2 VOLUME UP AND 3485 02:38:45,160 --> 02:38:48,720 3 WITH NOT VOLUME UP AND NONE OF 3486 02:38:48,720 --> 02:38:50,720 PATIENTS HAS REEXPANSION OR 3487 02:38:50,720 --> 02:38:54,200 REAPPEARANCE OF B CELL APLASIA 3488 02:38:54,200 --> 02:39:02,000 AFTER CAR 2 DOING FOR RELAPSE 8 3489 02:39:02,000 --> 02:39:05,880 PATIENTS IN HOSPITAL WITH THIS 3490 02:39:05,880 --> 02:39:09,880 DEPARTMENT AND ONE RESPOND TO 3491 02:39:09,880 --> 02:39:11,720 REESTABLISHMENT OF CR POST CAR 2 3492 02:39:11,720 --> 02:39:13,360 AND UNFORTUNATELY YOU CAN SEE 3493 02:39:13,360 --> 02:39:16,880 MOST OF THE PATIENTS HAVE DIED. 3494 02:39:16,880 --> 02:39:20,000 ONLY TWO PATIENTS ARE ALIVE AND 3495 02:39:20,000 --> 02:39:22,560 INTERESTINGLY, ONE HAS RECEIVED 3496 02:39:22,560 --> 02:39:27,240 DONOR DER I'VED CAR T-CELL AFTER 3497 02:39:27,240 --> 02:39:31,200 TWO FAILING OF CAR T-CELL AND 1 3498 02:39:31,200 --> 02:39:34,200 IS ALIVE AT THESE AND 3499 02:39:34,200 --> 02:39:35,120 ADMINISTERED THIS WHICH HAS 3500 02:39:35,120 --> 02:39:37,560 BROUGHT THEM TO CR. 3501 02:39:37,560 --> 02:39:40,240 SO, I HAVE ASKED MY DEER 3502 02:39:40,240 --> 02:39:42,560 COLLEAGUE FROM LONDON AND BARS 3503 02:39:42,560 --> 02:39:45,480 LONA AND MUNSTER AND TEL AVIV 3504 02:39:45,480 --> 02:39:47,000 AND ZURICH WHAT THEIR EXPERIENCE 3505 02:39:47,000 --> 02:39:49,440 IS AND IF WE PUT WITH OUR 3506 02:39:49,440 --> 02:39:52,560 EXPERIENCE IF YOU USE 3507 02:39:52,560 --> 02:39:53,960 REINFUSIONS TO TRY TO HAVE A 3508 02:39:53,960 --> 02:39:57,920 RETURN TO BCA AFTER LOSS OF B 3509 02:39:57,920 --> 02:40:02,880 CELL APLASIA, OVERALL OUT OF 39 3510 02:40:02,880 --> 02:40:06,640 PATIENTS 29% HAVE RETURN TO B 3511 02:40:06,640 --> 02:40:10,920 CELL APLASIA AND 4 OUT OF 5 WERE 3512 02:40:10,920 --> 02:40:15,080 TRANSIENT AND BASICALLY NOT VERY 3513 02:40:15,080 --> 02:40:17,680 HIGH SUCCESS RATE AND IN TERMS 3514 02:40:17,680 --> 02:40:20,560 OF KALGS IN RELAPSE DATA IS ALSO 3515 02:40:20,560 --> 02:40:26,680 DISAPPOINTING 4 OUT OF 21 SO 19% 3516 02:40:26,680 --> 02:40:28,760 CR RATE AFTER REINFUSION. 3517 02:40:28,760 --> 02:40:32,040 WE HAVE EMBARKED AND 3518 02:40:32,040 --> 02:40:34,080 UNFORTUNATELY I HAVE NO DATA TO 3519 02:40:34,080 --> 02:40:36,760 SHOW YOU ON DUE TO PRECLINICAL 3520 02:40:36,760 --> 02:40:40,240 DATA AND ALSO EXPERIENCE OF 3521 02:40:40,240 --> 02:40:43,200 SHANNON AND SHOP GROUP WITH 3522 02:40:43,200 --> 02:40:45,320 [INDISCERNIBLE]. WE HAVE 3523 02:40:45,320 --> 02:40:47,800 EMBARKED ON CAR T-CELL 3524 02:40:47,800 --> 02:40:49,320 REINFUSION TRIAL AND PATIENTS 3525 02:40:49,320 --> 02:40:52,040 WITH LAST B CELL APLASIA WITHIN 3526 02:40:52,040 --> 02:40:54,720 FIRST 6 MONTHS AND DESIGN AND 3527 02:40:54,720 --> 02:40:56,200 ADAPTIVE TRIAL WHERE VOLUME UP 3528 02:40:56,200 --> 02:41:02,920 WILL BE DEPENDING ON THE 3529 02:41:02,920 --> 02:41:05,400 REASSESSMENT METHOD AND MORE AND 3530 02:41:05,400 --> 02:41:10,680 MORE CLOSE TO THE REINFUSION OF 3531 02:41:10,680 --> 02:41:11,360 THE CAR. 3532 02:41:11,360 --> 02:41:15,800 DAY 14 AND 11 AND AT MOMENT NO 3533 02:41:15,800 --> 02:41:18,120 DATA ARE AVAILABLE FOR THESE 3534 02:41:18,120 --> 02:41:19,840 COHORTS AND IN TERMS OF 3535 02:41:19,840 --> 02:41:21,720 CONCLUSION OF REINFUSION DATA 3536 02:41:21,720 --> 02:41:25,040 WITHIN LIMITS OF RETROSPECTIVE 3537 02:41:25,040 --> 02:41:26,280 SMALL NUMBERS AND LOTS OF 3538 02:41:26,280 --> 02:41:28,920 CONFOUNDING FACTORS, IF WE SPEAK 3539 02:41:28,920 --> 02:41:32,760 ABOUT RELAPSE PREVENTION FOR 3540 02:41:32,760 --> 02:41:34,600 EARLY LOSS OF B CELL APLASIA 3541 02:41:34,600 --> 02:41:36,760 THERE ARE DISCREPANCIES 3542 02:41:36,760 --> 02:41:40,480 OBVIOUSLY AND NO CLEAR TREND FOR 3543 02:41:40,480 --> 02:41:42,360 MAJOR EFFICACY. 3544 02:41:42,360 --> 02:41:45,480 IF WE WANT TO PURSUE STRATEGY, 3545 02:41:45,480 --> 02:41:47,240 WE HAVE TO FIRST THINK ABOUT 3546 02:41:47,240 --> 02:41:50,400 ACTING EARLIER AND FOR EXAMPLE 3547 02:41:50,400 --> 02:41:53,080 BONE MARROW B CELL RECOVERY AND 3548 02:41:53,080 --> 02:41:54,240 INCLUDE PATIENTS IN CLINICAL 3549 02:41:54,240 --> 02:41:58,200 TRIALS AND HUMANIZE IF AVAILABLE 3550 02:41:58,200 --> 02:41:59,800 AND REINFUSION PLUS SOMETHING 3551 02:41:59,800 --> 02:42:01,760 AND DIDN'T PUT ON SLIDES 3552 02:42:01,760 --> 02:42:06,000 INTERESTING PRELIMINARY DATA OF 3553 02:42:06,000 --> 02:42:08,120 SARAN GROUP USING MAINTENANCE 3554 02:42:08,120 --> 02:42:10,400 THERAPY AVAILABLE. 3555 02:42:10,400 --> 02:42:14,240 BUT, ANYWAY, IF EVEN IF YOU 3556 02:42:14,240 --> 02:42:17,320 THINK ABOUT ESTABLISHING SECOND 3557 02:42:17,320 --> 02:42:21,440 B CELL APLASIA WITH FIRST TWO 3558 02:42:21,440 --> 02:42:23,360 BULLET POINTS YOU COULD QUESTION 3559 02:42:23,360 --> 02:42:25,520 DURABILITY OF THE SEBLGD B CELL 3560 02:42:25,520 --> 02:42:28,600 APLASIA. OF NOTE, FACT THAT 3561 02:42:28,600 --> 02:42:30,760 PROPORTION OF PATIENTS COMING TO 3562 02:42:30,760 --> 02:42:33,800 CAR T1 WITH HISTORY OF 3563 02:42:33,800 --> 02:42:37,840 TRANSPLANT DECREASED 60% TO LESS 3564 02:42:37,840 --> 02:42:39,600 THAN 20% MARCELO SHOWED DATA 3565 02:42:39,600 --> 02:42:41,680 THIS MORNING COULD RENDER 3566 02:42:41,680 --> 02:42:42,720 TRANSPLANT AS POTENTIAL OPTION 3567 02:42:42,720 --> 02:42:45,960 IN MANY CASES AND IN CASE OF 3568 02:42:45,960 --> 02:42:47,640 NONRESPONSE TO CAR T1 NO 3569 02:42:47,640 --> 02:42:49,360 INDICATION OF REINFUSION AND IN 3570 02:42:49,360 --> 02:42:50,520 CASE OF RELAPSE TREATMENT YOU 3571 02:42:50,520 --> 02:42:54,960 HAVE SEEN ON MY SLIDES CR RATE 3572 02:42:54,960 --> 02:42:59,400 IS BETWEEN 0 AND 50% MAYBE 25 3573 02:42:59,400 --> 02:43:03,040 AND ANY CASE DURABILITY AND 3574 02:43:03,040 --> 02:43:05,120 [INDISCERNIBLE] ARE NO TREATMENT 3575 02:43:05,120 --> 02:43:06,640 AND MAYBE THESE ARE 3576 02:43:06,640 --> 02:43:08,960 DISAPPOINTING AND WOULD LIKE TO 3577 02:43:08,960 --> 02:43:10,800 THAK CLAUDIO AND NICO FOR 3578 02:43:10,800 --> 02:43:14,720 SHARING INFUSION DATA AND THANKS 3579 02:43:14,720 --> 02:43:24,920 VERY MUCH. 3580 02:43:27,320 --> 02:43:36,360 >> GREAT TO SEE EVERYONE IN 3581 02:43:36,360 --> 02:43:38,600 PERSON. TITLE OF TALK IS POST 3582 02:43:38,600 --> 02:43:42,200 CAR RELAPSE PHENOTYPE AND 3583 02:43:42,200 --> 02:43:43,480 REIMPLICATIONS AND WE HAVE 3584 02:43:43,480 --> 02:43:46,720 ADDRESSED THAT CAR IS GREAT AT 3585 02:43:46,720 --> 02:43:49,320 INDUCING REMISSION AND RELAPSE 3586 02:43:49,320 --> 02:43:50,880 REMAINS A CHALLENGE AND PART OF 3587 02:43:50,880 --> 02:43:53,040 THIS TALK IS NOT ONLY IS RELAPSE 3588 02:43:53,040 --> 02:43:55,280 A CHALLENGE AND SURVIVAL OF 3589 02:43:55,280 --> 02:43:57,120 FOLLOWING RELAPSE OF CAR 3590 02:43:57,120 --> 02:43:59,760 INFUSION AND TWO PAPERS I WILL 3591 02:43:59,760 --> 02:44:01,200 REALLY HIGHLIGHT THROUGHOUT THE 3592 02:44:01,200 --> 02:44:02,880 TALK AND FIRST IS FROM 3593 02:44:02,880 --> 02:44:05,200 [INDISCERNIBLE] CONSORTIUM AS WE 3594 02:44:05,200 --> 02:44:06,680 TALKED ABOUT A FEW TIMES LIKE 3595 02:44:06,680 --> 02:44:10,800 THREE DIFFERENT CD19 CARS AND 3596 02:44:10,800 --> 02:44:13,720 419 PATIENTS AND SECOND FROM 3597 02:44:13,720 --> 02:44:14,960 PEDIATRIC REAL WORLD CONSORTIUM 3598 02:44:14,960 --> 02:44:18,240 THEY LOOKED AT OUTCOMES 3599 02:44:18,240 --> 02:44:20,080 FOLLOWING CHIMERA AND YOU SEE 3600 02:44:20,080 --> 02:44:22,520 FROM THESE KAPLAN MEYER 3601 02:44:22,520 --> 02:44:24,080 [INDISCERNIBLE] FOR OVERALL 3602 02:44:24,080 --> 02:44:25,840 SURVIVAL THAT FOLLOWING EVENT 3603 02:44:25,840 --> 02:44:28,360 AFTER INFUSION OUTCOMES ARE VERY 3604 02:44:28,360 --> 02:44:31,640 POOR WITH OVERALL SURVIVAL 3605 02:44:31,640 --> 02:44:32,520 APPROACHING ABOUT 20%. 3606 02:44:32,520 --> 02:44:34,480 THERE IS A LOT OF WAYS TO THINK 3607 02:44:34,480 --> 02:44:36,840 ABOUT RELAPSE FOLLOWING CAR. I 3608 02:44:36,840 --> 02:44:39,080 THINK THERE IS KIND OF PROS AND 3609 02:44:39,080 --> 02:44:40,600 CONS TO EACH OF THESE AND THINK 3610 02:44:40,600 --> 02:44:42,440 ABOUT THE MECHANISM OF RELAPSE 3611 02:44:42,440 --> 02:44:46,440 AND CLOSELY RELATED TO THAT IS 3612 02:44:46,440 --> 02:44:47,600 IMMUNOPHENOTYPE AND PRESENCE OR 3613 02:44:47,600 --> 02:44:51,080 ABSENCE OF CD19 THAT WILL BE 3614 02:44:51,080 --> 02:44:52,560 PRIMARY FOCUS OF MY TALK. THEN 3615 02:44:52,560 --> 02:44:55,000 WE HAVE TALKED A LOT ABOUT 3616 02:44:55,000 --> 02:44:57,000 TIMING OF RELAPSE AND LATE 3617 02:44:57,000 --> 02:44:58,920 VERSUS EARLY NOT NECESSARILY 3618 02:44:58,920 --> 02:45:00,880 ARBITRARY AND 6 MONTHS BEING A 3619 02:45:00,880 --> 02:45:02,800 CUTOFF WE TYPICALLY THINK ABOUT 3620 02:45:02,800 --> 02:45:04,720 AND ALL THESE REALLY INFORM 3621 02:45:04,720 --> 02:45:08,880 TREATMENT OPTIONS AVAILABLE TO A 3622 02:45:08,880 --> 02:45:15,000 PATIENT. THIS IS A CHART 3623 02:45:15,000 --> 02:45:16,320 SUMMARIZING LANDMARK THAT WE 3624 02:45:16,320 --> 02:45:18,240 DISCUSSED TODAY AND IS 3625 02:45:18,240 --> 02:45:19,920 REMARKABLE REMISSION AND RELAPSE 3626 02:45:19,920 --> 02:45:22,040 RATES THAT ARE RELATIVELY 3627 02:45:22,040 --> 02:45:23,280 SIMILAR BETWEEN TRIALS AND 3628 02:45:23,280 --> 02:45:26,120 REALLY ON THESE EARLY TRIALS WE 3629 02:45:26,120 --> 02:45:28,520 TALKED ABOUT RELAPSES PRESENCE 3630 02:45:28,520 --> 02:45:31,920 OR ABSENCE OF CD19 AND WASN'T 3631 02:45:31,920 --> 02:45:33,680 TALK ABOUT LINEAGE SWITCH AND 3632 02:45:33,680 --> 02:45:34,960 PROBABLY THOSE THAT ARE CAPTURE 3633 02:45:34,960 --> 02:45:38,760 THE IN CD19 NEGATIVE GROUP OR 3634 02:45:38,760 --> 02:45:41,240 RARE PHENOMENON CAPTURED IN SOME 3635 02:45:41,240 --> 02:45:44,160 SMALLER TRIALS SEEMS TO BE LIGHT 3636 02:45:44,160 --> 02:45:47,800 PREVENS TOWARDS CD19 TOWARDS 3637 02:45:47,800 --> 02:45:49,360 POSITIVE RELAPSES AND 3638 02:45:49,360 --> 02:45:50,920 EXPERIENCES EVOLVING STARTING 3639 02:45:50,920 --> 02:45:55,120 PATIENT POPULATIONS THAT ARE 3640 02:45:55,120 --> 02:45:55,600 ALSO EVOLVING. 3641 02:45:55,600 --> 02:45:57,480 WITHIN WHAT WE WANT TO DO WHAT 3642 02:45:57,480 --> 02:46:00,240 IS REALLY WE WANT TO DEFINE 3643 02:46:00,240 --> 02:46:02,120 CUMULATIVE INCIDENCE OF RELAPSE 3644 02:46:02,120 --> 02:46:06,520 BASED OFF PATTERN OF 3645 02:46:06,520 --> 02:46:10,160 IMMUNOPHENOTYPE AND THIS KAPLAN 3646 02:46:10,160 --> 02:46:13,920 MEYER CURVE ON LEFT AND GREEN IS 3647 02:46:13,920 --> 02:46:15,120 LINEAGE SWITCH AND CHART AT 3648 02:46:15,120 --> 02:46:18,200 BOTTOM IS LOOKING AT 24 MONTH 3649 02:46:18,200 --> 02:46:19,800 CUMULATIVE INCIDENCE RELAPSE OF 3650 02:46:19,800 --> 02:46:22,960 ALL THOSE AND COHORT WE SAW 42% 3651 02:46:22,960 --> 02:46:27,120 CIR AND CD19 POSITIVE IS 22 PS 3652 02:46:27,120 --> 02:46:30,560 CD19 NEGATIVE AND IS 16% AND 12 3653 02:46:30,560 --> 02:46:33,200 PATIENTS OR 3% THAT EXPERIENCE 3654 02:46:33,200 --> 02:46:35,880 LINEAGE SWITCH AND CD19 POSITIVE 3655 02:46:35,880 --> 02:46:37,680 AND NEGATIVE VAST MAJORITY OF 3656 02:46:37,680 --> 02:46:41,320 THOSE HAPPEN IN FIRST 1 TO 2 3657 02:46:41,320 --> 02:46:43,240 YEARS FOLLOWING INFUSION 3658 02:46:43,240 --> 02:46:44,440 FOLLOWING PATIENTS OUT FOR 3659 02:46:44,440 --> 02:46:45,720 SEVERAL YEARS WE ARE SEEING 3660 02:46:45,720 --> 02:46:48,320 SEVERAL LATE RELAPSES IN BOTH 3661 02:46:48,320 --> 02:46:49,800 COHORTS IN CONTRAST TO SWITCH 3662 02:46:49,800 --> 02:46:52,480 AND FOR THE MOST PART IF A 3663 02:46:52,480 --> 02:46:54,040 PATIENT HAS LINEAGE SWITCH THEY 3664 02:46:54,040 --> 02:46:56,760 HAVE IT IN 6 TO 12 MONTHS 3665 02:46:56,760 --> 02:46:57,800 FOLLOWING INFUSION AND AGAIN 3666 02:46:57,800 --> 02:47:01,600 JUST REMARKABLY SIMILAR RESULTS 3667 02:47:01,600 --> 02:47:02,880 FROM PEDIATRIC REAL WORLD 3668 02:47:02,880 --> 02:47:05,600 CONSORTIUM WITH CD19 POSITIVE 3669 02:47:05,600 --> 02:47:09,240 RELAPSES IN RED AND CD19 3670 02:47:09,240 --> 02:47:11,320 NEGATIVE RELAPSES IN GREEN AND 3671 02:47:11,320 --> 02:47:12,440 SLIGHT PREFERENCE TOWARDS 3672 02:47:12,440 --> 02:47:15,360 CONSIDER. D19 POSITIVE RELAPSES 3673 02:47:15,360 --> 02:47:19,480 I SUSPECT THEY FOLLOW PATIENTS 3674 02:47:19,480 --> 02:47:26,680 OUT FURTHER AND IT WILL CONTINUE 3675 02:47:26,680 --> 02:47:30,640 TO TAKE UP AND PREINFUSION 3676 02:47:30,640 --> 02:47:33,080 VARIABLES PREDICTIVE OF RELAPSE 3677 02:47:33,080 --> 02:47:35,080 THAT PATIENT MIGHT HAVE AND 3678 02:47:35,080 --> 02:47:39,240 REJENA SHARED ABOUT PREINFUSION 3679 02:47:39,240 --> 02:47:39,800 CHARACTERISTICS PREDICTING 3680 02:47:39,800 --> 02:47:41,560 RELAPSE AND LOOKING AT IF 3681 02:47:41,560 --> 02:47:43,320 PATIENT HAS RELAPSE IS THERE WAY 3682 02:47:43,320 --> 02:47:45,680 TO PREDICT WHAT RELAPSE THEY 3683 02:47:45,680 --> 02:47:47,680 HAVE? AGE AND GENDER AND 3684 02:47:47,680 --> 02:47:50,200 GENETICS AND TYPE OF CAR AND 3685 02:47:50,200 --> 02:47:51,720 PREVIOUS TREATMENT INCLUDING 3686 02:47:51,720 --> 02:47:53,920 STEM CELL TRANSPLANT AND DISEASE 3687 02:47:53,920 --> 02:47:56,200 BURDEN, ET CETERA. WE SAW FOR 3688 02:47:56,200 --> 02:47:57,640 CD19 POSITIVE RELAPSE THERE IS 3689 02:47:57,640 --> 02:48:00,280 NOT A LOT COMING OUT IN 3690 02:48:00,280 --> 02:48:02,440 MULTIVARIATE ANALYSIS AND 3691 02:48:02,440 --> 02:48:03,640 CUMULATIVE NUMBER OF REMISSIONS 3692 02:48:03,640 --> 02:48:06,800 AND CONTRAST CD19 NEGATIVE 3693 02:48:06,800 --> 02:48:08,280 RELAPSE SEVERAL VARIABLES CAME 3694 02:48:08,280 --> 02:48:11,040 OUT AND YOUNGER ANL AND ABSENCE 3695 02:48:11,040 --> 02:48:14,560 OF 41BB CAR AND HIGH DISEASE 3696 02:48:14,560 --> 02:48:17,120 BURDEN AND NONRESPONSE AND A FEW 3697 02:48:17,120 --> 02:48:18,560 OTHER GROUPS REPORTED SIMILAR 3698 02:48:18,560 --> 02:48:20,360 FINDINGS SPECIFICALLY RELATING 3699 02:48:20,360 --> 02:48:23,240 TO 41BB CAR AND HIGH DISEASE 3700 02:48:23,240 --> 02:48:25,920 BURDEN AND THOSE TRANSLATE TO 3701 02:48:25,920 --> 02:48:29,000 LONGER PERSISTENCE AND WE KNOW 3702 02:48:29,000 --> 02:48:30,640 SUSTAINED IMMUNOTHERAPEUTIC 3703 02:48:30,640 --> 02:48:33,600 PRESSURE IS IMPORTANT FOR CD19 3704 02:48:33,600 --> 02:48:35,040 NEGATIVE RELAPSES AND SWITCH WE 3705 02:48:35,040 --> 02:48:39,320 SAW THAT CAME OUT PRESENCE OF 3706 02:48:39,320 --> 02:48:41,160 KM22A ARRANGEMENT OBSERVATIONS 3707 02:48:41,160 --> 02:48:42,240 THAT GROUPS MADE AND WE FOUND 3708 02:48:42,240 --> 02:48:44,320 THAT IS STRIKING IS PATIENTS 3709 02:48:44,320 --> 02:48:48,760 THAT CAME TO 22A ARRANGEMENT 3710 02:48:48,760 --> 02:48:57,400 RELAPSE 6 60% ARE -- AND WHAT 3711 02:48:57,400 --> 02:48:59,720 ABOUT PROGNOSIS BASED OFF 3712 02:48:59,720 --> 02:49:02,600 PATTERN OF RELAPSE? 3713 02:49:02,600 --> 02:49:05,040 AGAIN ON LEFT-HAND SIDE GREEN 3714 02:49:05,040 --> 02:49:08,360 REPRESENTS LINEAGE SWITCH AND 12 3715 02:49:08,360 --> 02:49:09,440 PATIENTS EXPERIENCING LINEAGE 3716 02:49:09,440 --> 02:49:13,240 SWITCH THERE WERE NO LONG TERM 3717 02:49:13,240 --> 02:49:15,400 SURVIVAL AND DISMAL OUTCOME FOR 3718 02:49:15,400 --> 02:49:18,520 PATIENTS AND EARLY ON AT 2 YEARS 3719 02:49:18,520 --> 02:49:23,600 SEEM THE LIKE CD19 POSITIVE 3720 02:49:23,600 --> 02:49:25,520 PATIENTS ARE OVERALL -- 3721 02:49:25,520 --> 02:49:28,160 TARGETING STRATEGIES FOLLOWING 3722 02:49:28,160 --> 02:49:29,520 PATIENTS OUT A LITTLE FURTHER 3723 02:49:29,520 --> 02:49:33,160 CURVES HAVE OVERLAPPED CD19 3724 02:49:33,160 --> 02:49:35,000 NEGATIVE PATIENTS AND PEDIATRIC 3725 02:49:35,000 --> 02:49:37,840 REAL WORLD CONSORTIUM VERY 3726 02:49:37,840 --> 02:49:40,120 SIMILAR DATA AT 2 YEARS THAT 3727 02:49:40,120 --> 02:49:41,600 FOLLOW PATIENTS AND CURVES MIGHT 3728 02:49:41,600 --> 02:49:52,080 COME A LITTLE CLOSER TOGETHER DO 3729 02:49:52,080 --> 02:49:53,880 PATIENTS HAVE THIS IN RELAPSE 3730 02:49:53,880 --> 02:49:57,720 AND EARLY ON PATIENTS COME TO 3731 02:49:57,720 --> 02:50:02,000 CARS MULTIPLY RELAPSE AND 3732 02:50:02,000 --> 02:50:03,280 CHEMORESDIFLTANT DISEASE AND 3733 02:50:03,280 --> 02:50:05,800 LARGE CUMULATIVE TREATMENT 3734 02:50:05,800 --> 02:50:07,280 BURDEN STEM CELL PLANT LEADING 3735 02:50:07,280 --> 02:50:11,000 TO COMORBIDITIES AND LEADING TO 3736 02:50:11,000 --> 02:50:12,040 STEM CELL TRANSPLANT AND 3737 02:50:12,040 --> 02:50:14,520 IMPORTANT IS REDUCED 3738 02:50:14,520 --> 02:50:16,120 IMMUNOTHERAPEUTIC OPTIONS 3739 02:50:16,120 --> 02:50:17,440 DEPENDING ON PATTERN OF RELAPSE 3740 02:50:17,440 --> 02:50:19,360 THAT IS AN EXERCISE THAT WE DO 3741 02:50:19,360 --> 02:50:22,040 WHEN WE HAVE A PATIENT TREATED 3742 02:50:22,040 --> 02:50:24,200 WITH CAR T-CELLS WHEN THEY 3743 02:50:24,200 --> 02:50:26,200 RELAPSE IS AN ALGORITHM THAT I 3744 02:50:26,200 --> 02:50:30,280 PUT IN NUMBERS THAT I GENERATED 3745 02:50:30,280 --> 02:50:34,080 FROM CONSORTIUM AND PATIENT ARE 3746 02:50:34,080 --> 02:50:36,880 CD19 POSITIVE -- THEY HAVE 60% 3747 02:50:36,880 --> 02:50:39,640 CHANCE SUSTAINED REMISSION 3748 02:50:39,640 --> 02:50:42,000 WHETHER DURABLE REMISSION OR 3749 02:50:42,000 --> 02:50:44,560 CONSOLIDATED WITH TRANSPLANT AND 3750 02:50:44,560 --> 02:50:47,680 CONTRAST 22% EXPERIENCE POSITIVE 3751 02:50:47,680 --> 02:50:53,040 RELAPSE AND 15% EXPERIENCE 3752 02:50:53,040 --> 02:50:56,040 NEGATIVE RELAPSE AND EXPERIENCE 3753 02:50:56,040 --> 02:50:58,080 NEGATIVE SWITCH AND CD19 3754 02:50:58,080 --> 02:51:00,160 POSITIVE PATIENTS THEY CAN YOU 3755 02:51:00,160 --> 02:51:05,640 CAN TARGET CD19 ANTIGENS FOR 3756 02:51:05,640 --> 02:51:08,240 REINFUSION AND ALTERNATIVE CAR 3757 02:51:08,240 --> 02:51:10,600 PRODUCT AND YOU HAVE ALL CD22 3758 02:51:10,600 --> 02:51:12,840 OPTIONS AND OF COURSE CAN PIVOT 3759 02:51:12,840 --> 02:51:15,120 BACK TO CHEMOTHERAPY AND THAT 3760 02:51:15,120 --> 02:51:17,240 PRIMARILY IF YOU TARGET CD19 OWE 3761 02:51:17,240 --> 02:51:19,200 MGSS AND WE ARE TALKING MORE AND 3762 02:51:19,200 --> 02:51:23,480 MORE ABOUT CHEMOTHERAPY OR L- 3763 02:51:23,480 --> 02:51:27,360 LONG TERM BLINA AND PERHAPS 3764 02:51:27,360 --> 02:51:28,680 PATIENTS COULD GET A LONG 3765 02:51:28,680 --> 02:51:30,720 RESPONSE AND BE ALLOCATED TO 3766 02:51:30,720 --> 02:51:33,480 STEM CELL TRANSPLANT AND 3767 02:51:33,480 --> 02:51:37,120 CONTRAST CD19 RELAPSES POSITIVE 3768 02:51:37,120 --> 02:51:39,240 OPTIONS AND CD2 TARGETING 3769 02:51:39,240 --> 02:51:40,360 OPTIONS AND FOR MOST PART SHOULD 3770 02:51:40,360 --> 02:51:43,160 BE ALLOCATED TO TRANCE PLANT 3771 02:51:43,160 --> 02:51:45,560 THAT IS SIMILAR FOR LINEAGE 3772 02:51:45,560 --> 02:51:47,760 SWITCH. WE DON'T KNOW WHAT BEST 3773 02:51:47,760 --> 02:51:49,360 TREATMENT APPROACH SHOULD BE FOR 3774 02:51:49,360 --> 02:51:50,680 LINEAGE SWITCH. IF YOU ARE ABLE 3775 02:51:50,680 --> 02:51:53,160 TO GET A PATIENT INTO REMISSION 3776 02:51:53,160 --> 02:51:55,000 PROBABLY SHOULD BE ALLOCATED TO 3777 02:51:55,000 --> 02:51:56,720 TRANSPLANT THAT IS A VERY 3778 02:51:56,720 --> 02:51:58,360 SIMPLIFIED ALGORITHM WE ARE 3779 02:51:58,360 --> 02:52:00,480 LOOKING AT BINARY RELATIONSHIP 3780 02:52:00,480 --> 02:52:02,880 BETWEEN CD19 AND AS EVERYBODY 3781 02:52:02,880 --> 02:52:04,280 KNOWS IT IS MUCH MORE 3782 02:52:04,280 --> 02:52:05,600 COMPLICATED THAN THAT AND 3783 02:52:05,600 --> 02:52:08,320 PRIMARILY INCORPORATING CD22 AND 3784 02:52:08,320 --> 02:52:11,400 SOME PATIENTS COMING INTO CARS 3785 02:52:11,400 --> 02:52:12,480 AND RECEIVING [INDISCERNIBLE] 3786 02:52:12,480 --> 02:52:16,760 AND PERHAPS SALVAGED WITH CD22 3787 02:52:16,760 --> 02:52:18,960 CARS AND GETS COMPLICATED FROM 3788 02:52:18,960 --> 02:52:20,680 THERE AND INFORMING DIFFERENT 3789 02:52:20,680 --> 02:52:22,000 TREATMENT OPTIONS AND FOCUS OF 3790 02:52:22,000 --> 02:52:25,480 OUR GROUP IS LOOKING AT ANTIGEN 3791 02:52:25,480 --> 02:52:26,640 NEGATIVE OR LINEAGE SWITCH 3792 02:52:26,640 --> 02:52:27,560 PATIENTS WHERE WE DON'T KNOW 3793 02:52:27,560 --> 02:52:29,600 WHAT TO DO WITH THEM OR WHAT 3794 02:52:29,600 --> 02:52:33,160 BEST TREATMENT IS AND THIS IS AN 3795 02:52:33,160 --> 02:52:34,800 INSTITUTIONAL EXPERIENCE AND 3796 02:52:34,800 --> 02:52:38,720 ANECDOTES WHAT WE TRIED FOR 3797 02:52:38,720 --> 02:52:40,480 PATIENTS WITHOUT GREAT 3798 02:52:40,480 --> 02:52:42,040 IMMUNOTARGETS AND GENERALLY WE 3799 02:52:42,040 --> 02:52:48,000 ARE GIVING INTENSIVE MILOID 3800 02:52:48,000 --> 02:52:49,960 DIRECTIVE THERAPY AND INHIBITOR 3801 02:52:49,960 --> 02:52:51,760 TRIALS AND WE HAVE SEEN YOU KNOW 3802 02:52:51,760 --> 02:52:54,680 ARE REALLY ENCOURAGING SIGNAL IN 3803 02:52:54,680 --> 02:52:57,920 PATIENTS WITH AML AND THEY SEEM 3804 02:52:57,920 --> 02:52:59,600 LIKE REASONABLE AGENT FOR AML 3805 02:52:59,600 --> 02:53:01,080 THAT IS REASONABLE FOR PATIENTS 3806 02:53:01,080 --> 02:53:02,880 AND IMMUNOTHERAPY TRIALS AND 3807 02:53:02,880 --> 02:53:05,800 TARGETS AND TRYING TO GET 3808 02:53:05,800 --> 02:53:07,440 PATIENTS TO TRANSPLANT AND 3809 02:53:07,440 --> 02:53:09,640 FINALLY, LAST THING TO CALL OUT 3810 02:53:09,640 --> 02:53:11,880 IS A UNIQUE PHENOMENON WE HAVE 3811 02:53:11,880 --> 02:53:15,040 SEEN IN A FEW PATIENTS DISEASE 3812 02:53:15,040 --> 02:53:17,120 PLASTICITY FOLLOWING LINEAGE 3813 02:53:17,120 --> 02:53:20,480 SWITCH AND BLUE LINE IS FLOW 3814 02:53:20,480 --> 02:53:25,600 DETECTIBLE ALL AND RED IS FLOW 3815 02:53:25,600 --> 02:53:28,040 DETECTIBLE AML AND GREEN IS 3816 02:53:28,040 --> 02:53:29,800 [INDISCERNIBLE] AND THIS IS 3817 02:53:29,800 --> 02:53:32,000 PATIENT WITH PERSISTENT DISEASE 3818 02:53:32,000 --> 02:53:37,680 AND GOT CD19 BY CD22 T-CELL AND 3819 02:53:37,680 --> 02:53:40,560 FLOW RAISED REMISSION AND HAD 3820 02:53:40,560 --> 02:53:43,720 LINEAGE SWITCH TREATING WITH 3821 02:53:43,720 --> 02:53:44,880 INTENSIVE MYELOID DIRECTIVE 3822 02:53:44,880 --> 02:53:46,280 THERAPY AND GOT TO REMISSION AND 3823 02:53:46,280 --> 02:53:48,800 WEPT TO TRANSPLANT AND AFTER 3824 02:53:48,800 --> 02:53:51,240 TRANSPLANT THEY REOCCURRED WITH 3825 02:53:51,240 --> 02:53:54,160 CD19 POSITIVE A WILL. L. 3826 02:53:54,160 --> 02:53:56,080 WE DID RECHALLENGE PATIENT AND 3827 02:53:56,080 --> 02:53:58,120 THERE WAS CONCERN THAT IF THEY 3828 02:53:58,120 --> 02:54:00,040 HAD LINEAGE SWITCH IN THE 3829 02:54:00,040 --> 02:54:01,240 BEGINNING THEY MIGHT BE 3830 02:54:01,240 --> 02:54:02,840 PREDETERMINE THE TO HAVE LINEAGE 3831 02:54:02,840 --> 02:54:07,200 SWITCH AND THEY HAVE BEEN IN 3832 02:54:07,200 --> 02:54:10,320 CLONO SEEK REMISSION AND 3833 02:54:10,320 --> 02:54:11,120 PERCEIVED MAINTENANCE AND 3834 02:54:11,120 --> 02:54:14,280 REPORTED WITH A SIMILAR PATIENT 3835 02:54:14,280 --> 02:54:16,840 WITH IDENTICAL PHENOMENON OCCUR 3836 02:54:16,840 --> 02:54:18,280 AND SWITCH IS RARE AND WE DON'T 3837 02:54:18,280 --> 02:54:20,960 HAVE LOTS OF DATA ON HOW IT IS 3838 02:54:20,960 --> 02:54:22,560 DIAGNOSED OR TREATED AND PLUG 3839 02:54:22,560 --> 02:54:25,520 FOR RETROSPECTIVE ANALYSIS AND 3840 02:54:25,520 --> 02:54:27,800 IF YOU HAVE A PATIENT 3841 02:54:27,800 --> 02:54:30,240 EXPERIENCING THIS NOT JUST FROM 3842 02:54:30,240 --> 02:54:31,680 CAR T-CELLS OR THIS WE WOULD 3843 02:54:31,680 --> 02:54:34,240 LOVE TO HEAR ABOUT IT AND IF 3844 02:54:34,240 --> 02:54:35,840 INTERESTED IN PARTICIPATING 3845 02:54:35,840 --> 02:54:40,120 E-MAIL ME AT NIRALI SHAH AT 3846 02:54:40,120 --> 02:54:42,680 NIH.GOV. FOR SAKE OF TIME I 3847 02:54:42,680 --> 02:54:43,880 WILL SKIP THROUGH THE SUMMARY 3848 02:54:43,880 --> 02:54:46,840 AND SAY THANK YOU. 3849 02:54:46,840 --> 02:54:53,200 >> [APPLAUSE]. 3850 02:54:53,200 --> 02:54:57,240 >> THANK YOU FINAL SPEAKER IS 3851 02:54:57,240 --> 02:54:59,200 NIRALI TALKING ABOUT 3852 02:54:59,200 --> 02:55:05,920 [INDISCERN 3853 02:55:05,920 --> 02:55:06,320 [INDISCERNIBLE]. 3854 02:55:06,320 --> 02:55:09,320 >> THANK YOU, EVERYBODY. 3855 02:55:09,320 --> 02:55:13,840 TALKING ABOUT COMBIN TORIAL 3856 02:55:13,840 --> 02:55:23,400 STRATEGIES. COMBIN ATORIAL 3857 02:55:23,400 --> 02:55:27,240 STRATEGIES ARE BASED IN ALL. 3858 02:55:27,240 --> 02:55:28,960 [INDISCERNIBLE] CLEARLY ALL OF 3859 02:55:28,960 --> 02:55:31,200 THE COMBIN ATORIAL STRATEGIES 3860 02:55:31,200 --> 02:55:32,760 SEQUENCING THEM IN AND 3861 02:55:32,760 --> 02:55:34,360 SEPARATING THEM OUT LED TO 3862 02:55:34,360 --> 02:55:37,360 IMPROVED OUTCOMES OVER TIME AND 3863 02:55:37,360 --> 02:55:43,640 ANTIGEN LOSS IS PRIMARY CAUSE OF 3864 02:55:43,640 --> 02:55:44,520 [INDISCERNIBLE]. THE OTHER 3865 02:55:44,520 --> 02:55:45,800 THING I THINK IS A LITTLE 3866 02:55:45,800 --> 02:55:49,520 INTERESTING AND DON'T KNOW IT IS 3867 02:55:49,520 --> 02:55:52,840 FULLY EVALUATIVE EVEN LOSS OF 3868 02:55:52,840 --> 02:55:54,280 CD19 IN EXPRESSED 3869 02:55:54,280 --> 02:55:57,080 [INDISCERNIBLE] WHEN YOU LOSE 3870 02:55:57,080 --> 02:55:58,440 CD19CD22 ALSO TENDS TO 3871 02:55:58,440 --> 02:56:03,240 DOWNREGULATE AND THIS IS LOOKING 3872 02:56:03,240 --> 02:56:06,960 AT PATIENTS. 3873 02:56:06,960 --> 02:56:10,280 RETENTION OF CD19 AND FOLLOWING 3874 02:56:10,280 --> 02:56:12,760 IT IS LOOKING AT CD22 EXPRESSION 3875 02:56:12,760 --> 02:56:15,200 IN SAMPLES THAT ARE IN PATIENTS 3876 02:56:15,200 --> 02:56:17,240 THAT ARE SUBSEQUENTLY CD19 3877 02:56:17,240 --> 02:56:18,480 NEGATIVE AND YOU SEE HERE THERE 3878 02:56:18,480 --> 02:56:20,800 IS I MEAN THERE IS NO 3879 02:56:20,800 --> 02:56:22,120 EXPLANATION WHY YOU WOULD LOSE 3880 02:56:22,120 --> 02:56:23,560 CD22 ALONG WITH IT AND IS 3881 02:56:23,560 --> 02:56:26,480 SOMETHING WE ARE STARTING TO 3882 02:56:26,480 --> 02:56:29,000 SEE. ANOTHER EXAMPLE LOOKING AT 3883 02:56:29,000 --> 02:56:34,920 FLOW DOT PLOTS CD22 ON LEFT AND 3884 02:56:34,920 --> 02:56:39,840 CD19 ON X AXIS YOU HAVE CD19 3885 02:56:39,840 --> 02:56:42,000 NEGATIVE POPULATION AND PARTIAL 3886 02:56:42,000 --> 02:56:44,200 EXPRESSION OF CD22. 3887 02:56:44,200 --> 02:56:48,200 SO, JUST SPEAKING QUICKLY ABOUT 3888 02:56:48,200 --> 02:56:50,760 CD22 CAR T-CELLS AND INITIAL 3889 02:56:50,760 --> 02:56:55,240 THAT HAS MOST LONGEVITY IN TERMS 3890 02:56:55,240 --> 02:56:58,240 OF EFFICACY IS SHOWING OVERALL 3891 02:56:58,240 --> 02:57:00,040 CAR T-CELL CONSTRUCT AND BASED 3892 02:57:00,040 --> 02:57:03,240 ON RESULTS IT IS FIRST IN HUMAN 3893 02:57:03,240 --> 02:57:07,760 AND FIRST IN CHILD EXPERIENCE. 3894 02:57:07,760 --> 02:57:12,720 ON SAME DISEASE WE APPLIED 3895 02:57:12,720 --> 02:57:13,520 RECEIVING BREAK THROUGH THERAPY 3896 02:57:13,520 --> 02:57:18,360 SEVERAL YEARS AGO AND SHOWING 3897 02:57:18,360 --> 02:57:22,800 OVERALL -- BOTTOM LINE HIGHLY 3898 02:57:22,800 --> 02:57:24,320 EFFECTIVE 70% COMPLETE REMISSION 3899 02:57:24,320 --> 02:57:31,840 RATES AND CD19 NEGATIVE DISEASE 3900 02:57:31,840 --> 02:57:32,200 RATES. 3901 02:57:32,200 --> 02:57:35,480 WE LEARNED THAT CRS SEVERITY IS 3902 02:57:35,480 --> 02:57:39,000 WLOEER THAN NEUROTOXICITY IS 3903 02:57:39,000 --> 02:57:41,480 SUBSTANTIALLY MILDER AND THAT 3904 02:57:41,480 --> 02:57:42,760 CD22 EXPRESSION OVERALL WAS EVEN 3905 02:57:42,760 --> 02:57:45,480 THOUGH IT IS ON A B CELL IT 3906 02:57:45,480 --> 02:57:48,360 DIFFERS FROM CD19 AND MANUSCRIPT 3907 02:57:48,360 --> 02:57:50,480 WE HAVE CURRENTLY IN REVIEW 3908 02:57:50,480 --> 02:57:52,960 LOOKING AT DIFFERENCES IN 3909 02:57:52,960 --> 02:57:53,920 NEUROTOXICITY AND WHY THEY MIGHT 3910 02:57:53,920 --> 02:57:55,200 BE DIFFERENT THERE AND KNOWING 3911 02:57:55,200 --> 02:57:58,000 YOU HAVE A DIFFERENT EFFECTIVE 3912 02:57:58,000 --> 02:58:00,480 CD22 CAR T-CELL AND EFFECTIVE 3913 02:58:00,480 --> 02:58:02,920 CD19 TARGETING THOUGHT IS HOW TO 3914 02:58:02,920 --> 02:58:07,240 TAKE THIS FORWARD THINKING OF 3915 02:58:07,240 --> 02:58:10,400 COMBIN ATORIAL CAR T-CELL 3916 02:58:10,400 --> 02:58:13,480 STRATEGIES AND GIVING CD19 CAR 3917 02:58:13,480 --> 02:58:15,400 AND THEY CAN BE DONE 3918 02:58:15,400 --> 02:58:16,880 SIMULTANEOUSLY AND THEY CAN BE 3919 02:58:16,880 --> 02:58:22,400 DONE IN CLOSE SEQUENCE OR SUB 3920 02:58:22,400 --> 02:58:30,480 WRITE IT OUT IS. 3921 02:58:30,480 --> 02:58:34,800 THERE ARE EFFECTIVES AND T-CELL 3922 02:58:34,800 --> 02:58:36,400 PRODUCT AND SEATTLE GROUP IS 3923 02:58:36,400 --> 02:58:37,920 TESTING THIS AND MODEL IS ONE 3924 02:58:37,920 --> 02:58:39,440 THAT WE HAVE A TRIAL THAT WE 3925 02:58:39,440 --> 02:58:42,240 OPENED THAT IS A SINGLE VECTOR 3926 02:58:42,240 --> 02:58:45,400 GOING INTO T-CELLS INTERNAL 3927 02:58:45,400 --> 02:58:48,280 CLEAVAGE AND SHOW THESE IN EQUAL 3928 02:58:48,280 --> 02:58:49,920 PROPORTION ON CELL SURFACE AND 3929 02:58:49,920 --> 02:58:52,080 HAVING A LITTLE MIX YOU HAVE ALL 3930 02:58:52,080 --> 02:58:57,760 YOUR T-CELLS EXPRESSING CD19 AND 3931 02:58:57,760 --> 02:58:59,960 CD22 AND YOU HAVE TANDEM MODELS 3932 02:58:59,960 --> 02:59:03,000 WITH ONE VECTOR GOING INTO THE 3933 02:59:03,000 --> 02:59:06,200 T-CELL AND BEING ABLE TO 3934 02:59:06,200 --> 02:59:07,200 RESPECTIVELY POTENTIALLY 3935 02:59:07,200 --> 02:59:17,760 EFFECTIVELY TARGET THAT AS WELL. 3936 02:59:18,360 --> 02:59:20,040 WALKING THROUGH STRATEGIES PROS 3937 02:59:20,040 --> 02:59:22,920 ARE YOU ARE ABLE TO TAKE TWO 3938 02:59:22,920 --> 02:59:25,480 EFFECTIVE CAR T-CELLS ENSURING 3939 02:59:25,480 --> 02:59:26,720 EFFICACY AND YOU HAVE TO MAKE 3940 02:59:26,720 --> 02:59:29,560 TWO DIFFERENT VECTORS AND CAR 3941 02:59:29,560 --> 02:59:31,560 T-CELL PRODUCTS AND THAT COULD 3942 02:59:31,560 --> 02:59:33,600 REALLY REPRESENT A HUGE 3943 02:59:33,600 --> 02:59:36,360 LOGISTICAL HURDLE TRYING TO DO 3944 02:59:36,360 --> 02:59:38,400 SOMETHING LIKE THIS IN 3945 02:59:38,400 --> 02:59:40,080 PEDIATRICS AND CONCERN FOR 3946 02:59:40,080 --> 02:59:42,160 SYNERGISTIC TOXICITY AND AGAIN 3947 02:59:42,160 --> 02:59:44,240 DEPENDING WHAT MODEL YOU USE 3948 02:59:44,240 --> 02:59:46,320 GIVEN TOGETHER LOWER DOSES OF 3949 02:59:46,320 --> 02:59:48,880 TWO GIVEN SIMULTANEOUSLY AND 3950 02:59:48,880 --> 02:59:50,520 INDUCTION AND SUBSEQUENTLY 3951 02:59:50,520 --> 02:59:51,560 CONSOLIDATION AND YOU MIGHT BE 3952 02:59:51,560 --> 02:59:53,680 ABLE TO ADDRESS IT AND GOT 3953 02:59:53,680 --> 02:59:56,000 BETTER AT ADDRESSING TOXICITY 3954 02:59:56,000 --> 02:59:58,520 AND COINFUSION STRATEGIES 3955 02:59:58,520 --> 03:00:01,640 SIMULTANEOUS OR PAPER PRESENTED 3956 03:00:01,640 --> 03:00:04,320 EARLIER. IT THIS IS WORK DONE 3957 03:00:04,320 --> 03:00:06,920 BY GROUP IN CHINA AND LARGEST 3958 03:00:06,920 --> 03:00:09,600 STUDY DONE PROSPECTIVELY IN 3959 03:00:09,600 --> 03:00:12,360 PEDIATRIC ALL. THEY HAD REALLY 3960 03:00:12,360 --> 03:00:13,520 EXCEPTIONAL OUTCOMES AND LARGE 3961 03:00:13,520 --> 03:00:15,560 PART OF PATIENT POPULATION IS 3962 03:00:15,560 --> 03:00:17,640 FIRST RELAPSE THAT IS CLEARLY 3963 03:00:17,640 --> 03:00:19,160 UNMET NEED FOR CHILDREN AT LEAST 3964 03:00:19,160 --> 03:00:22,000 IN THE UNITED STATES AND IN 3965 03:00:22,000 --> 03:00:24,960 EUROPE. 3966 03:00:24,960 --> 03:00:25,760 SEQUENTIAL SEATING HAD 3967 03:00:25,760 --> 03:00:26,400 OPPORTUNITY TO DO COMMENT AND 3968 03:00:26,400 --> 03:00:29,120 THEY ARE GETTING CD19 SORT OF 3969 03:00:29,120 --> 03:00:32,080 LIKE INDUCTION CD22 IN 3970 03:00:32,080 --> 03:00:34,040 CONSOLIDATION TO TRY TO IMPROVE 3971 03:00:34,040 --> 03:00:37,400 OVERALL DURABLE REMISSIONS AND 3972 03:00:37,400 --> 03:00:38,640 COTRANSDUCTION YOU HAVE A SINGLE 3973 03:00:38,640 --> 03:00:40,480 AND YOU HAVE [INDISCERNIBLE] AND 3974 03:00:40,480 --> 03:00:43,760 YOU ARE LEVERAGING DUAL EFFICACY 3975 03:00:43,760 --> 03:00:46,920 KNOWING THAT SINGLE ANTIGENS 3976 03:00:46,920 --> 03:00:49,920 WILL POTENTIALLY HAVE EFFICACY 3977 03:00:49,920 --> 03:00:52,520 NOT DUALLY TRANCE DEUCED PAYING 3978 03:00:52,520 --> 03:00:55,360 FOR TWO EFFECTORS AND 3979 03:00:55,360 --> 03:00:56,920 HETEROGENEITY IN TERMS OF FINAL 3980 03:00:56,920 --> 03:00:59,760 PRODUCT AND DATA SHARED WITH 3981 03:00:59,760 --> 03:01:02,000 REBECCA GARDENER BASED ON 3982 03:01:02,000 --> 03:01:03,480 STUDIES TWO DIFFERENT VERSIONS 3983 03:01:03,480 --> 03:01:07,640 USING CD22 AND ORIGINAL VERSION 3984 03:01:07,640 --> 03:01:11,160 INCORPORATING CD19 AND CD22 THAT 3985 03:01:11,160 --> 03:01:14,720 WAS NOT VERY EFFECTIVE AND 3986 03:01:14,720 --> 03:01:17,640 BREAKDOWN OF ACTUAL CAR T-CELLS 3987 03:01:17,640 --> 03:01:20,320 THEY HAD PRIMARILY THIS PRODUCT 3988 03:01:20,320 --> 03:01:23,240 AND CD22 IN TERMS OF OVERALL 3989 03:01:23,240 --> 03:01:25,360 EXPANSION AND LOOKING AT DUAL 3990 03:01:25,360 --> 03:01:27,640 TRANSDUCTION AND REVISE THE IT 3991 03:01:27,640 --> 03:01:31,880 LATER CD22 OPTIMIZED IT IMPROVED 3992 03:01:31,880 --> 03:01:33,600 EFFICACY AND YOU SEE EXPANSION 3993 03:01:33,600 --> 03:01:34,720 PARAMETERS ARE DIFFERENT AND YOU 3994 03:01:34,720 --> 03:01:38,680 END UP WITH LOTS MORE CD22 AND 3995 03:01:38,680 --> 03:01:40,480 LOTS OF BIOLOGY NEEDING TO BE 3996 03:01:40,480 --> 03:01:42,360 EXPLORED HERE IN TERMS OF 3997 03:01:42,360 --> 03:01:43,480 DIFFERENCES BETWEEN TWO AND THEY 3998 03:01:43,480 --> 03:01:46,360 ARE CURRENTLY WORKING ON 3999 03:01:46,360 --> 03:01:49,200 REVISING THEIR PROTOCOL A LITTLE 4000 03:01:49,200 --> 03:01:50,680 TO THINK ABOUT DOSING STRATEGIES 4001 03:01:50,680 --> 03:01:54,400 AND IN TERMS OF BIVAILANT WE 4002 03:01:54,400 --> 03:01:56,840 PUBLISHED DATA AGAIN THAT IS 4003 03:01:56,840 --> 03:01:58,240 SINGLE ACTIVATION SINGLE ONE 4004 03:01:58,240 --> 03:02:00,400 VECTOR THAT LOWERS COST AND 4005 03:02:00,400 --> 03:02:03,280 CAUSES I HAVE YET TO SEE DATA 4006 03:02:03,280 --> 03:02:06,880 DUAL TARGETING TO EFFECTIVELY 4007 03:02:06,880 --> 03:02:11,120 TARGET THIS SINGLE CAR T-CELL 4008 03:02:11,120 --> 03:02:14,360 STRATEGIES TARGETING WAS LESS 4009 03:02:14,360 --> 03:02:16,560 EFFECTIVE AND CLINICAL -- SHOWED 4010 03:02:16,560 --> 03:02:18,400 LIMITED PERSISTENCE THAT IS 4011 03:02:18,400 --> 03:02:20,800 PARTICULARLY PROBLEMATIC IN B 4012 03:02:20,800 --> 03:02:23,160 CELL ALL. SAME VECTOR IN 4013 03:02:23,160 --> 03:02:26,640 CONSTRUCT WAS USED IN LYMPHOMA 4014 03:02:26,640 --> 03:02:29,160 COHORT WONDERFUL AND LONG-TERM 4015 03:02:29,160 --> 03:02:31,960 RESULTS AND WE HAVE TO BE 4016 03:02:31,960 --> 03:02:34,520 COGNIZANT OF THE LIMITATION AND 4017 03:02:34,520 --> 03:02:35,560 WITH [INDISCERNIBLE] AND OUR 4018 03:02:35,560 --> 03:02:37,400 TRIAL IS CURRENTLY UP AND 4019 03:02:37,400 --> 03:02:40,680 RUNNING AND TREATED 1 PATIENT 4020 03:02:40,680 --> 03:02:43,240 AND SIMILAR TO BIVAILABILITY 4021 03:02:43,240 --> 03:02:46,000 SINGLE ACTIVATION SINGLE AND 4022 03:02:46,000 --> 03:02:49,360 UNIFORM PRODUCT AND THIS IS DATA 4023 03:02:49,360 --> 03:02:53,120 FROM PERSISTENT SARA'S GROUP IN 4024 03:02:53,120 --> 03:02:57,600 THE UK SHOW LIMITATIONS ON DUAL 4025 03:02:57,600 --> 03:02:59,000 TARGETING THAT IS LESS EFFECTIVE 4026 03:02:59,000 --> 03:03:01,480 AND PROBLEM WITH PERSISTENCE 4027 03:03:01,480 --> 03:03:02,160 USING SLIGHTLY DIFFERENT 4028 03:03:02,160 --> 03:03:05,160 CONSTRUCT AND GOING BACK TO WHAT 4029 03:03:05,160 --> 03:03:07,840 MAKES GOOD CAR T-CELL AND 4030 03:03:07,840 --> 03:03:10,680 POINTING OUT B CELL LYMPHOMA 4031 03:03:10,680 --> 03:03:14,320 VERSUS BCALL THERE ARE HUGE 4032 03:03:14,320 --> 03:03:16,120 DIFFERENCES BEING MINDFUL WHAT 4033 03:03:16,120 --> 03:03:18,760 PEDIATRIC DATA SHOWS IN PATIENTS 4034 03:03:18,760 --> 03:03:21,720 AND PATIENTS REQUIRE YEARS OF 4035 03:03:21,720 --> 03:03:23,360 THERAPY AND LYMPHOMA PATIENTS 4036 03:03:23,360 --> 03:03:28,360 HAVE NEVER REALLY REQUIRED THAT 4037 03:03:28,360 --> 03:03:29,000 THAT IS IMPORTANT AND -- AND I 4038 03:03:29,000 --> 03:03:30,560 THINK THAT THE OTHER THING IN 4039 03:03:30,560 --> 03:03:33,080 TERMS OF TRIAL IS WE ARE TAKING 4040 03:03:33,080 --> 03:03:34,920 PATIENTS RECEIVING PRIOR CAR 4041 03:03:34,920 --> 03:03:35,720 T-CELLS THAT WILL HAVE IMPACT 4042 03:03:35,720 --> 03:03:39,640 WHEN YOU ARE TRYING TO TEST A 4043 03:03:39,640 --> 03:03:42,720 NEW COMBIN ATORIAL STRATEGY AND 4044 03:03:42,720 --> 03:03:44,960 IMPACTING TRIALS FOR EFFICACY 4045 03:03:44,960 --> 03:03:46,280 AND PERSISTENCE AND IN 4046 03:03:46,280 --> 03:03:49,040 CONCLUSION DUAL ANCONTINUALEN 4047 03:03:49,040 --> 03:03:53,720 TARGETED APPROACHES MAY IMPROVE 4048 03:03:53,720 --> 03:03:58,560 OUTCOMES AND -- MAY BE COST 4049 03:03:58,560 --> 03:04:02,080 PROHIBITED AND NEED SECOND 4050 03:04:02,080 --> 03:04:03,280 PROJECT AVAILABLE AND CAR 4051 03:04:03,280 --> 03:04:05,600 T-CELLS WILL BE A NEED TO 4052 03:04:05,600 --> 03:04:08,240 OPTIMIZE UPON SINGLE ANTIGEN 4053 03:04:08,240 --> 03:04:10,960 TARGETING AND WORRY ABOUT 4054 03:04:10,960 --> 03:04:12,520 ANCONTINUALEN MODULATION EVEN IF 4055 03:04:12,520 --> 03:04:15,920 NOT DIRECTLY TARGETED WITH 4056 03:04:15,920 --> 03:04:17,080 SPECIFIC ANTIGEN AND SOMETHING 4057 03:04:17,080 --> 03:04:19,480 TO THINK ABOUT AND WE ARE OPEN 4058 03:04:19,480 --> 03:04:23,200 FOR QUESTIONS FOR THIS SESSION. 4059 03:04:23,200 --> 03:04:25,480 >> [APPLAUSE]. 4060 03:04:25,480 --> 03:04:28,360 >> THANK YOU, NIRALI AND ALL 4061 03:04:28,360 --> 03:04:31,640 SPEAKERS FOR A FANTASTIC 4062 03:04:31,640 --> 03:04:37,760 SESSION. QUESTIONS? 4063 03:04:37,760 --> 03:04:49,240 I THINK THE GRAPH YOU SHOWED WAS 4064 03:04:49,240 --> 03:04:52,680 COMPARING CD22 -- DO YOU ALSO 4065 03:04:52,680 --> 03:04:56,480 HAVE THAT SAME ANALYSIS 4066 03:04:56,480 --> 03:05:00,280 COMPARING THEIR PRE-TREATMENT 4067 03:05:00,280 --> 03:05:03,040 AND WHAT IS THE DIFFERENCE IN 22 4068 03:05:03,040 --> 03:05:06,080 EXPRESSION PRIOR TO TREATMENT 4069 03:05:06,080 --> 03:05:16,440 AND POST TREATMENT? 4070 03:05:19,920 --> 03:05:28,160 >> [INDISCERNIBLE]. 4071 03:05:28,160 --> 03:05:32,840 >> POST 19 TARGETED THERAPY 4072 03:05:32,840 --> 03:05:36,400 [INDISCERNIBLE] I WILL SAY THAT 4073 03:05:36,400 --> 03:05:38,640 COHORT [INDISCERNIBLE] WE WANTED 4074 03:05:38,640 --> 03:05:41,560 TO MAKE SURE IT WAS 4075 03:05:41,560 --> 03:05:43,040 [INDISCERNIBLE] POPULATION AND 4076 03:05:43,040 --> 03:05:53,600 IN PRECLINICAL [INDISCERNIBLE]. 4077 03:05:57,960 --> 03:06:01,960 >> I GUESS IT WAS A LEADING 4078 03:06:01,960 --> 03:06:06,840 QUESTION TO KNOW IS LOW DENSITY 4079 03:06:06,840 --> 03:06:09,920 2022 EXPRESSION A MARKER WHAT 4080 03:06:09,920 --> 03:06:13,040 WILL COME WITH CD19 RELAPSE? AS 4081 03:06:13,040 --> 03:06:17,360 THEY LOSE 19 DOES THAT TYPE OF 4082 03:06:17,360 --> 03:06:21,240 LEUKEMIA HAVE LOW 2022 4083 03:06:21,240 --> 03:06:22,080 EXPRESSION? 4084 03:06:22,080 --> 03:06:32,560 >> YEAH. [INDISCERNIBLE]. 4085 03:06:39,720 --> 03:06:43,000 >> COOL. THANKS. 4086 03:06:43,000 --> 03:06:46,440 >> I'M ASKING A QUESTION. ABOUT 4087 03:06:46,440 --> 03:06:48,240 NGS, YOU KNOW, RIGHT NOW THERE 4088 03:06:48,240 --> 03:06:50,760 IS ONLY ONE BIOTECH COMPANY THAT 4089 03:06:50,760 --> 03:06:53,360 CAN DO THAT FOR US. 4090 03:06:53,360 --> 03:06:56,720 BECAUSE IT IS VERY HARD. YOU 4091 03:06:56,720 --> 03:06:58,720 KNOW, IF YOU LOOK TO GET BELOW 4092 03:06:58,720 --> 03:07:03,240 10 TO THE FIFTH TACKING TO 4093 03:07:03,240 --> 03:07:06,440 MOLECULAR LABS WONDERING IF YOU 4094 03:07:06,440 --> 03:07:09,320 ARE WORRIED AND HAVING ACCESS TO 4095 03:07:09,320 --> 03:07:12,960 ROBUST NGS TESTING TO LESS TAN 4096 03:07:12,960 --> 03:07:16,560 10 TO THE 6 CAN YOU COMMENT ON 4097 03:07:16,560 --> 03:07:16,960 THAT? 4098 03:07:16,960 --> 03:07:19,880 >> SO, THIS IS A PROBLEM 4099 03:07:19,880 --> 03:07:21,440 CERTAINLY. NO ONE EXCEPT FOR 4100 03:07:21,440 --> 03:07:22,240 CUSTOMERS IN THE UNITED STATES 4101 03:07:22,240 --> 03:07:24,520 HAVE ACCESS TO IT AND IT IS 4102 03:07:24,520 --> 03:07:26,760 MOVING TO AUSTRALIA. DON'T KNOW 4103 03:07:26,760 --> 03:07:29,240 ABOUT EUROPE WHETHER ADAPTIVE IS 4104 03:07:29,240 --> 03:07:30,600 PLANNING TO DO ANYTHING IN 4105 03:07:30,600 --> 03:07:34,640 EUROPE. INTERESTINGLY ADAPTIVE 4106 03:07:34,640 --> 03:07:36,120 IS HAPPY TO CELL TECHNOLOGY AND 4107 03:07:36,120 --> 03:07:38,520 HAVE DONE THAT AND ARRANGED IT 4108 03:07:38,520 --> 03:07:41,160 IN AUSTRALIA AND VERY SOON WE 4109 03:07:41,160 --> 03:07:43,160 CAN DO IT IN AUSTRALIA. 4110 03:07:43,160 --> 03:07:45,320 ADAPTIVE IS DOING JUST FINE IT 4111 03:07:45,320 --> 03:07:47,280 IS ONE COMPANY AND VIGOROUS AND 4112 03:07:47,280 --> 03:07:49,240 VERY GOOD TESTING AND AS I 4113 03:07:49,240 --> 03:07:51,000 SHOWED IT REALLY MAKES A 4114 03:07:51,000 --> 03:07:52,560 DIFFERENCE TO GO AS DEEP AS YOU 4115 03:07:52,560 --> 03:07:53,320 CAN. 4116 03:07:53,320 --> 03:07:55,440 SO, I THINK THAT TECHNOLOGY WILL 4117 03:07:55,440 --> 03:07:59,160 BE HERE. WHAT I HOPE IS 4118 03:07:59,160 --> 03:08:01,920 ADAPTIVE FIGURES OUT A WAY TO 4119 03:08:01,920 --> 03:08:03,240 PARTNER WITH THOSE IN EUROPE 4120 03:08:03,240 --> 03:08:04,920 EUROPE IS CLOSE AND WILL GIVE A 4121 03:08:04,920 --> 03:08:07,360 GOOD SIGNAL IF POSITIVE WITH PCR 4122 03:08:07,360 --> 03:08:10,760 BAD THINGS WILL HAPPEN. IT IS 4123 03:08:10,760 --> 03:08:12,240 JUST BETTER IF YOU HAVE THE 4124 03:08:12,240 --> 03:08:14,560 DEEPER SIGNAL. I THINK IT WILL 4125 03:08:14,560 --> 03:08:16,680 BE AROUND FOR A WHILE. 4126 03:08:16,680 --> 03:08:18,880 >> GOOD. 4127 03:08:18,880 --> 03:08:20,840 >> [INDISCERNIBLE]. 4128 03:08:20,840 --> 03:08:31,360 >> >> SO, JUST TO REPEAT FOR THE 4129 03:08:49,880 --> 03:08:52,880 AUDIENCE AT HOME THE QUESTION IS 4130 03:08:52,880 --> 03:08:56,240 IS IT REALLY A PREDICTOR OF 4131 03:08:56,240 --> 03:08:59,400 RELAPSE OR LOW-LEVEL PERSISTENT 4132 03:08:59,400 --> 03:09:03,480 DISEASE? IT IS LOW-LEVEL 4133 03:09:03,480 --> 03:09:04,200 PERSISTENT DISEASE AND IMPORTANT 4134 03:09:04,200 --> 03:09:05,720 THING TO UNDERSTAND WE CAN DO 4135 03:09:05,720 --> 03:09:08,560 DIFFERENT THINGS BASED ON WHERE 4136 03:09:08,560 --> 03:09:09,920 THE DISEASE STARTS AND 4137 03:09:09,920 --> 03:09:11,640 TRANSPLANT IF YOU TRY TO 4138 03:09:11,640 --> 03:09:14,560 TRANSPLANT ALL PATIENT LESS -- 4139 03:09:14,560 --> 03:09:16,920 WITH MORE THAN 10 TO THE MINUS 3 4140 03:09:16,920 --> 03:09:19,280 AT TRANSPLANT, OUTCOME IS DISS 4141 03:09:19,280 --> 03:09:22,040 MAL AND RELAPSE RATE IS 4142 03:09:22,040 --> 03:09:23,440 EXCEPTIONALLY HIGH AND GETTING 4143 03:09:23,440 --> 03:09:26,080 THEM FLOW NEGATIVE WE ARE OKAY 4144 03:09:26,080 --> 03:09:28,160 HAVING DEEP IN NGS WE KNOW WE 4145 03:09:28,160 --> 03:09:30,120 CAN DO THINGS AND ALTHOUGH YES 4146 03:09:30,120 --> 03:09:32,880 IT IS JUST A MARKER OF 4147 03:09:32,880 --> 03:09:33,840 PERSISTENT DISEASE I THINK THAT 4148 03:09:33,840 --> 03:09:37,760 YOU WANT TO CALL IT A BIOMARKER. 4149 03:09:37,760 --> 03:09:39,240 PERSISTENT DISEASE YOU CAN DO 4150 03:09:39,240 --> 03:09:42,400 SOMETHING WITH AND THERAPIES 4151 03:09:42,400 --> 03:09:48,280 WILL BE GAUGED UPON WHETHER 4152 03:09:48,280 --> 03:09:51,160 THERE WILL BE A GOOD OUTCOME AND 4153 03:09:51,160 --> 03:09:52,960 IMPORTANT TO UNDERSTAND PATIENTS 4154 03:09:52,960 --> 03:09:55,240 FLOW NEGATIVE AND NGS POSITIVE 4155 03:09:55,240 --> 03:09:57,680 IT IS NOT BAD AND YOU CAN 4156 03:09:57,680 --> 03:09:59,600 SALVAGE MORE THAN 50% OF THEM 4157 03:09:59,600 --> 03:10:02,320 AND WE SHOWED AT LAST TANDEM 4158 03:10:02,320 --> 03:10:08,720 MEETING AND IS PERSISTENT TO 4159 03:10:08,720 --> 03:10:08,920 SEE. 4160 03:10:08,920 --> 03:10:11,000 >> THANK YOU. 4161 03:10:11,000 --> 03:10:12,200 >> QUESTION IS TO 4162 03:10:12,200 --> 03:10:13,160 [INDISCERNIBLE] AND SECOND 4163 03:10:13,160 --> 03:10:16,560 INFUSION OF FM63 AND SINGLE 4164 03:10:16,560 --> 03:10:18,000 CHAIN BINDING PRODUCT AND YOU 4165 03:10:18,000 --> 03:10:20,480 LOSE VERY SOON OR HAS TEMPORARY 4166 03:10:20,480 --> 03:10:23,000 EFFICACY IT IS OBVIOUS 4167 03:10:23,000 --> 03:10:24,640 IMMUNOLOGICAL REJECTION COULD BE 4168 03:10:24,640 --> 03:10:26,320 INVOLVED IN THIS PHENOMENON THAT 4169 03:10:26,320 --> 03:10:28,320 IS OBVIOUS AND I'M NOT AWARE OF 4170 03:10:28,320 --> 03:10:32,880 ANYONE HAVING SHOWN IT. ARE 4171 03:10:32,880 --> 03:10:37,760 YOU? 4172 03:10:37,760 --> 03:10:40,720 >> THANK YOU. HAS BEEN WORK 4173 03:10:40,720 --> 03:10:43,280 FROM SEATTLE GROUP AND DON'T 4174 03:10:43,280 --> 03:10:45,560 KNOW. MOSTLY FROM ADULT STUDIES 4175 03:10:45,560 --> 03:10:47,080 YOU MIGHT BE ABLE TO COMMENT TO 4176 03:10:47,080 --> 03:10:51,880 THAT. YOU KNOW, THEY HAD 4177 03:10:51,880 --> 03:10:53,200 DETECTED T-CELL RESPONSES 4178 03:10:53,200 --> 03:10:56,160 LEADING TO IMMUNE LOGIC 4179 03:10:56,160 --> 03:10:58,120 REJECTION. WE DO NOT HAVE 4180 03:10:58,120 --> 03:11:03,440 DEFINITIVE DATA SHOWING THAT. 4181 03:11:03,440 --> 03:11:05,160 NEVARTIS LOOKED AT PHASE 2 4182 03:11:05,160 --> 03:11:07,040 TRIALS AND HAVE NOT DETECTED 4183 03:11:07,040 --> 03:11:07,320 THAT. 4184 03:11:07,320 --> 03:11:11,320 I WOULD SAY THAT I THINK AS I 4185 03:11:11,320 --> 03:11:14,840 HAVE SAID TO THEM ABOUT DATA 2, 4186 03:11:14,840 --> 03:11:16,320 I THINK LACK OF DETECTION 4187 03:11:16,320 --> 03:11:18,760 DOESN'T MEAN IT IS NOT THERE BUT 4188 03:11:18,760 --> 03:11:20,880 IS A HARD THING TO LOOK FOR AND 4189 03:11:20,880 --> 03:11:22,680 FIND AND WE NEED TO LOOK FOR IT 4190 03:11:22,680 --> 03:11:24,600 IN OTHER WAYS. BUT, SOMETHING 4191 03:11:24,600 --> 03:11:27,120 THAT WE STILL NEED TO WORK ON. 4192 03:11:27,120 --> 03:11:30,480 >> ANYONE WORKED IT OUT IN VITRO 4193 03:11:30,480 --> 03:11:34,360 TRYING TO GROW? I MEAN IT WOULD 4194 03:11:34,360 --> 03:11:39,640 ONLY BE AN INDICATOR. 4195 03:11:39,640 --> 03:11:43,320 >> AS A WAY TO PREDICT? 4196 03:11:43,320 --> 03:11:47,720 >> PORTION OF FM63. 4197 03:11:47,720 --> 03:11:48,600 >> OH. 4198 03:11:48,600 --> 03:11:52,840 >> TO RAISE CTL RESPONSES TO 4199 03:11:52,840 --> 03:11:57,160 REJECT ADDITIONAL FURTHER CTLS. 4200 03:11:57,160 --> 03:12:02,080 >> YEAH. IT HASN'T BEEN 4201 03:12:02,080 --> 03:12:03,640 WELL-CHARACTERIZED. WOULD 4202 03:12:03,640 --> 03:12:07,040 T-CELL RESPONSE ASSAYS DO IT BY 4203 03:12:07,040 --> 03:12:08,920 PULLING DIFFERENT SECTIONS OF IT 4204 03:12:08,920 --> 03:12:12,600 IT HASN'T BEEN CHARACTERIZED. 4205 03:12:12,600 --> 03:12:22,840 >> THANK YOU. 4206 03:12:33,440 --> 03:12:34,280 >> [INDISCERNIBLE]. 4207 03:12:34,280 --> 03:12:36,040 >> CAN YOU REPEAT QUESTION? 4208 03:12:36,040 --> 03:12:39,280 >> YEAH. CAN YOU HEAR ME? 4209 03:12:39,280 --> 03:12:41,480 QUESTION WAS HAVE WE CONSIDERED 4210 03:12:41,480 --> 03:12:48,320 GIVING CD19APCS BOOSTER STRATEGY 4211 03:12:48,320 --> 03:12:52,080 PRECAR AND NO. WE HAVE NOT IS 4212 03:12:52,080 --> 03:12:53,920 THE SHORT ANSWER AND WAY WE 4213 03:12:53,920 --> 03:12:56,720 DESIGNED TRIAL IS TO DO IT AFTER 4214 03:12:56,720 --> 03:12:58,880 AND INTRIGUING IDEA TO HAVE THAT 4215 03:12:58,880 --> 03:13:01,840 SETUP TO HAVE ENERGY BURDEN FROM 4216 03:13:01,840 --> 03:13:04,000 THE GET-GO AND BRAND NEW PRODUCT 4217 03:13:04,000 --> 03:13:05,440 WITHOUT KNOWING WHAT TO EXPECT 4218 03:13:05,440 --> 03:13:07,240 OR DO WE HADN'T CONSIDERED THAT 4219 03:13:07,240 --> 03:13:09,320 AND THINK THAT SOME THINGS ABOUT 4220 03:13:09,320 --> 03:13:12,760 THIS ARBITRARILY ARE CHOSEN TOO. 4221 03:13:12,760 --> 03:13:14,760 DOSING AND TIMEFRAME WE DECIDED 4222 03:13:14,760 --> 03:13:16,480 FIRST IN HUMAN TRIAL AND 4223 03:13:16,480 --> 03:13:19,080 TWEAKING WE CAN DO TIMING OF 4224 03:13:19,080 --> 03:13:20,880 TAPCS WHEN WE START THEM AND 4225 03:13:20,880 --> 03:13:22,520 DOING THIS MOVING IT FORWARD HOW 4226 03:13:22,520 --> 03:13:24,360 LONG TO GIVE THEM AND HOW LONG 4227 03:13:24,360 --> 03:13:26,440 THEY NEED DOSING AND IF DOSE 4228 03:13:26,440 --> 03:13:28,640 ITSELF COULD BE OPTIMIZED AND WE 4229 03:13:28,640 --> 03:13:35,640 HAVE THAT TYPE OF WORK TO DO. 4230 03:13:35,640 --> 03:13:36,960 >> 4231 03:13:36,960 --> 03:13:38,800 >> GREAT TALKS ALL AROUND AND 4232 03:13:38,800 --> 03:13:40,440 STUFF WE ARE STRUGGLING WITH AND 4233 03:13:40,440 --> 03:13:42,000 INFORMATION WE SOMETIMES DON'T 4234 03:13:42,000 --> 03:13:45,840 KNOW WHAT TO DO WITH. YOUR 4235 03:13:45,840 --> 03:13:50,640 POINT MIKE ABOUT POTENTIAL 4236 03:13:50,640 --> 03:13:52,480 EFFICACY GOING TO THAT MODALITY 4237 03:13:52,480 --> 03:13:55,280 IS SOMETHING TO AFFIRMATIVELY 4238 03:13:55,280 --> 03:13:56,720 EITHER EMBRACE OR NOT. 4239 03:13:56,720 --> 03:13:58,920 I THINK THAT MORE DATA WE HAVE 4240 03:13:58,920 --> 03:14:02,360 IN THAT AREA THE BETTER AND 4241 03:14:02,360 --> 03:14:03,640 PRESENTATION WAS A REALLY 4242 03:14:03,640 --> 03:14:06,880 IMPORTANT IN THAT REGARD. IN MY 4243 03:14:06,880 --> 03:14:08,360 FAVORITE TOPIC OF TRANSPLANT I 4244 03:14:08,360 --> 03:14:09,920 WOULD LIKE TO PUT A COUPLE 4245 03:14:09,920 --> 03:14:11,200 THINGS TOGETHER HEARING FROM ALL 4246 03:14:11,200 --> 03:14:14,400 OF THE PRESENTATIONS AND ONE IS 4247 03:14:14,400 --> 03:14:16,840 THE OBSERVATION THAT FEWER AND 4248 03:14:16,840 --> 03:14:18,600 FEWER AND ANDRÉ YOU MADE THIS 4249 03:14:18,600 --> 03:14:20,680 POINT OF THE RELAPSES WE ARE 4250 03:14:20,680 --> 03:14:23,240 SEEING THAT ARE NEGATIVE AFTER 4251 03:14:23,240 --> 03:14:23,760 COMMERCIAL CAR. 4252 03:14:23,760 --> 03:14:26,320 AND THAT MAY HAVE AN IMPACT ON A 4253 03:14:26,320 --> 03:14:31,200 NUMBER OF THINGS. THE UP-FRONT 4254 03:14:31,200 --> 03:14:34,760 COG STUDY AND GENERAL ISSUE OF 4255 03:14:34,760 --> 03:14:37,440 IF THERE IS SAME PERSISTENCE WE 4256 03:14:37,440 --> 03:14:38,680 DON'T KNOW ANSWER TO THAT 4257 03:14:38,680 --> 03:14:40,520 QUESTION AND IS IMPORTANT TO 4258 03:14:40,520 --> 03:14:42,040 ACKNOWLEDGE THAT PERSISTENCE HAS 4259 03:14:42,040 --> 03:14:45,000 TAKEN A DIP IN THE COMMERCIAL 4260 03:14:45,000 --> 03:14:47,600 ERA THAT IS HOPEFULLY COMING UP 4261 03:14:47,600 --> 03:14:50,800 AND WHAT WE KNOW FROM PUBLIC 4262 03:14:50,800 --> 03:14:55,880 DATA IS NOVARIS CHANGED APPROACH 4263 03:14:55,880 --> 03:14:59,280 AND SOMEWHAT LESS PERSISTENT AND 4264 03:14:59,280 --> 03:15:02,320 CHARACTERISTICS GETTING PATIENTS 4265 03:15:02,320 --> 03:15:05,040 INTO REMISSION AND SHORT TERM NO 4266 03:15:05,040 --> 03:15:07,480 PROBLEM AND LONGER TERM AND 4267 03:15:07,480 --> 03:15:08,240 MEETING EXPECTATIONS HIGHER 4268 03:15:08,240 --> 03:15:11,200 LEVEL OF CD19 POSITIVE RELAPSE 4269 03:15:11,200 --> 03:15:14,000 AND LOWER LEVEL CD19 RELAPSE 4270 03:15:14,000 --> 03:15:16,200 GOES ALONG WITH THAT AND IS 4271 03:15:16,200 --> 03:15:17,680 INDIRECT AND PROBABLY TRUE AND 4272 03:15:17,680 --> 03:15:19,440 WE DON'T KNOW AND I'M 4273 03:15:19,440 --> 03:15:20,360 HYPOTHESIZING THAT IS THE CASE 4274 03:15:20,360 --> 03:15:22,280 AND I HOPE THIS IS REALLY THE 4275 03:15:22,280 --> 03:15:24,200 COMMENT I WOULD LIKE TO HEAR 4276 03:15:24,200 --> 03:15:26,000 ANYBODY'S COMMENTS ON THIS IS 4277 03:15:26,000 --> 03:15:31,120 THAT WITH RESTORATION OF 4278 03:15:31,120 --> 03:15:32,280 NOVARTIS MANUFACTURING APPROACH 4279 03:15:32,280 --> 03:15:34,200 WHAT THEY PROCESS AS F THAT IS 4280 03:15:34,200 --> 03:15:36,520 INFORMATION THAT IS BACK TO THE 4281 03:15:36,520 --> 03:15:37,880 SORT OF MEDIAN CHARACTERISTICS 4282 03:15:37,880 --> 03:15:39,440 THAT THEY STARTED WITH THAT WILL 4283 03:15:39,440 --> 03:15:41,200 BE BACK IN A SITUATION WHERE WE 4284 03:15:41,200 --> 03:15:44,240 SEE THAT, YOU KNOW, 50% 4285 03:15:44,240 --> 03:15:47,720 LONG-TERM B CELL APLASIA WE SAW 4286 03:15:47,720 --> 03:15:51,640 NEXT LIANA AND OTHER STUDIES AND 4287 03:15:51,640 --> 03:15:53,240 IF FOLKS FEEL THAT IS THE CASE 4288 03:15:53,240 --> 03:15:55,480 THEY DON'T HAVE DATA TO ADDRESS 4289 03:15:55,480 --> 03:15:57,240 IT BUT CHANGING CHARACTERISTICS 4290 03:15:57,240 --> 03:16:01,760 OF CD19 POSITIVE VERSUS CD19 4291 03:16:01,760 --> 03:16:03,640 NEGATIVE MIGHT BE A CLUE. 4292 03:16:03,640 --> 03:16:05,880 >> IT IS LEVEL OF DISEASE AT 4293 03:16:05,880 --> 03:16:06,880 TREATMENT ALSO. MUST HAVE 4294 03:16:06,880 --> 03:16:08,320 SOMETHING TO DO WITH IT. 4295 03:16:08,320 --> 03:16:10,120 >> MUST HAVE SOMETHING? 4296 03:16:10,120 --> 03:16:10,320 SORRY. 4297 03:16:10,320 --> 03:16:12,120 >> I THINK IF YOU LOOK AT REAL 4298 03:16:12,120 --> 03:16:14,320 WORLD DATA SO MANY PATIENTS ARE 4299 03:16:14,320 --> 03:16:18,200 TREATED AT A LOWER LEVEL OF 4300 03:16:18,200 --> 03:16:23,680 DISEASE. SO TROUBLE IS I WOULD 4301 03:16:23,680 --> 03:16:34,080 LOVE FOR FORM LALGS F? 4302 03:16:39,760 --> 03:16:41,680 >> THAT IS RIGHT. TWO THINGS 4303 03:16:41,680 --> 03:16:43,480 ARE HAPPENING AND MAYBE THERE IS 4304 03:16:43,480 --> 03:16:45,800 FOR SURE DISRUPTION IN THE 4305 03:16:45,800 --> 03:16:47,440 PRODUCT AND MAYBE EFFECTED 4306 03:16:47,440 --> 03:16:49,560 QUALITY AND SAME TIME WE 4307 03:16:49,560 --> 03:16:51,920 TRANSPLANT PATIENTS AT LOWER 4308 03:16:51,920 --> 03:16:52,160 LEVELS. 4309 03:16:52,160 --> 03:16:52,960 >> GREAT POINT. 4310 03:16:52,960 --> 03:16:54,720 >> OF DISEASE AND DON'T KNOW HOW 4311 03:16:54,720 --> 03:16:57,240 TO TEASE IT APART BUT HAVE TO 4312 03:16:57,240 --> 03:16:58,720 THINK CAREFULLY ABOUT IT. 4313 03:16:58,720 --> 03:17:01,920 >> COMMENTING ON THAT IS A GREAT 4314 03:17:01,920 --> 03:17:04,040 POINT AND THERE ARE OR HAVE BEEN 4315 03:17:04,040 --> 03:17:06,440 DATA THAT IS SHOWING THAT 4316 03:17:06,440 --> 03:17:07,480 PATIENTS WITH HIGH DISEASE 4317 03:17:07,480 --> 03:17:12,760 BURDEN ARE LIKELY TO RELAPSE IN 4318 03:17:12,760 --> 03:17:13,720 19 NEGATIVE DISEASE AND HOWEVER 4319 03:17:13,720 --> 03:17:15,640 I THINK THAT NUMBER OF THE 4320 03:17:15,640 --> 03:17:17,920 PROPORTION OF PATIENTS RELAPSING 4321 03:17:17,920 --> 03:17:20,760 WITH COMMERCIAL PRODUCT IS 4322 03:17:20,760 --> 03:17:22,360 HOLDING KIND OF STEADY WITH WHAT 4323 03:17:22,360 --> 03:17:25,480 WE WERE SEEING ON INITIAL PHASE 4324 03:17:25,480 --> 03:17:27,880 1 TRIAL AND ELIANA TRIAL AND YOU 4325 03:17:27,880 --> 03:17:31,080 EXPECT WITH PATIENTS WITH LOWER 4326 03:17:31,080 --> 03:17:34,400 DISEASE BURDEN THERE WOULD BE 4327 03:17:34,400 --> 03:17:38,240 FEWER PATIENTS RELAPSING AND 4328 03:17:38,240 --> 03:17:39,920 HIGHER PROPORTION OF 19 POSITIVE 4329 03:17:39,920 --> 03:17:42,200 RELAPSES AND SEEING THEM IS 4330 03:17:42,200 --> 03:17:44,840 SUGGESTING WE ARE SEEING POORER 4331 03:17:44,840 --> 03:17:45,640 PERSISTENCE AND QUESTION IS 4332 03:17:45,640 --> 03:17:46,760 WHETHER IT GOT BETTER WITH A 4333 03:17:46,760 --> 03:17:49,480 CHANGE AND DO WE HAVE LONG 4334 03:17:49,480 --> 03:17:50,920 ENOUGH DATA TO KNOW THAT? 4335 03:17:50,920 --> 03:17:51,960 >> THANK YOU EVERYBODY. IN 4336 03:17:51,960 --> 03:17:53,240 INTEREST OF TIME WE HAVE TO MOVE 4337 03:17:53,240 --> 03:17:55,560 TO THE NEXT EVENT THAT IS A 4338 03:17:55,560 --> 03:17:57,560 GROUP PHOTO IN THE BACK. 4339 03:17:57,560 --> 03:17:59,920 AND LUNCH. 4340 03:17:59,920 --> 03:18:04,000 >> WE WILL GET STARTED THIS IS 4341 03:18:04,000 --> 03:18:06,760 THIRD SESSION PREVENTION AND 4342 03:18:06,760 --> 03:18:09,560 MANAGEMENT AND WILL START WITH 4343 03:18:09,560 --> 03:18:12,080 REBEKAH GARDNER FROM SEATTLE 4344 03:18:12,080 --> 03:18:15,920 CHILDREN'S TALKING ABOUT 4345 03:18:15,920 --> 03:18:17,800 PRE-EMPTIVE PROPHYLACTIVE 4346 03:18:17,800 --> 03:18:18,680 OPTIONS FOR CF. 4347 03:18:18,680 --> 03:18:21,360 >> I WILL TRY NOT TO BE OFFENDED 4348 03:18:21,360 --> 03:18:25,040 THAT NOBODY CAME BACK FOR MY 4349 03:18:25,040 --> 03:18:28,480 TALK. 4350 03:18:28,480 --> 03:18:37,720 JUST KIDDING. 4351 03:18:37,720 --> 03:18:39,600 APPARENTLY I DON'T KNOW HOW TO 4352 03:18:39,600 --> 03:18:42,200 WORK A COMPUTER EITHER. 4353 03:18:42,200 --> 03:18:43,560 THERE WE GO. 4354 03:18:43,560 --> 03:18:46,120 NOW IT IS GOING. 4355 03:18:46,120 --> 03:18:48,680 OKAY. SO, I AM HAPPY TO TALK TO 4356 03:18:48,680 --> 03:18:53,480 YOU ABOUT PRE-EMPTIVE AND 4357 03:18:53,480 --> 03:18:55,520 PROPHYLACTIVE STRATEGIES 4358 03:18:55,520 --> 03:18:58,000 FOR-CRS. CHALLENGE TO DO IN 8 4359 03:18:58,000 --> 03:19:00,040 MINUTES AND WILL DO MY BEST AND 4360 03:19:00,040 --> 03:19:01,640 A LOT OF INFORMATION WON'T BE 4361 03:19:01,640 --> 03:19:04,080 INCLUDED BUT WE CAN TALK ABOUT 4362 03:19:04,080 --> 03:19:06,720 IT WITH OUR DISCUSSION. 4363 03:19:06,720 --> 03:19:09,560 THIS EARLY INTERVENTION AFTER WE 4364 03:19:09,560 --> 03:19:11,320 TREATED 20 MASHIENTS AND MANY 4365 03:19:11,320 --> 03:19:13,520 GOING TO ICU AND STARTED TO 4366 03:19:13,520 --> 03:19:17,400 NOTICE WHEN ADMINISTERING 4367 03:19:17,400 --> 03:19:19,080 STEROIDS PATIENTS WERE HAVING 4368 03:19:19,080 --> 03:19:20,600 ROBUST EXPANSION GETTING INTO 4369 03:19:20,600 --> 03:19:22,080 COMPLETE REMISSIONS AND STARTED 4370 03:19:22,080 --> 03:19:24,400 TO CHANGE R OUR STRATEGY AND DO 4371 03:19:24,400 --> 03:19:27,200 INTERVENTION EARLY ON WITH 4372 03:19:27,200 --> 03:19:29,920 PERSISTENT SYMPTOMS OF MILD CRS 4373 03:19:29,920 --> 03:19:32,240 TO PREVENT MILD CRS. THIS IS A 4374 03:19:32,240 --> 03:19:34,640 GRAPH OF OUR STRATEGY THAT IS 4375 03:19:34,640 --> 03:19:37,120 ESSENTIALLY HAVING PERSISTENT 4376 03:19:37,120 --> 03:19:38,600 FEVERS AND RECURRENT 4377 03:19:38,600 --> 03:19:40,400 HYPERTENSION NOT RESPONDING TO 4378 03:19:40,400 --> 03:19:44,120 FLUID BOLISES OR REFUSING OXYGEN 4379 03:19:44,120 --> 03:19:45,440 SUPPLEMENTATION AND ADMINISTERED 4380 03:19:45,440 --> 03:19:51,800 T OWE, SIE. IF SYMPTOMS 4381 03:19:51,800 --> 03:19:53,760 PROGRESSED -- HOWEVER AFTER 48 4382 03:19:53,760 --> 03:19:55,600 HOURS YOU COULD GET A SECOND 4383 03:19:55,600 --> 03:19:58,200 DOSE OF TOESEE. IN THE GRAPHS 4384 03:19:58,200 --> 03:20:00,880 YOU CAN SEE IN THE COHORT BEFORE 4385 03:20:00,880 --> 03:20:03,120 EARLIER INTERVENTION YOU SEE A 4386 03:20:03,120 --> 03:20:06,280 DIFFERENCE IN MAX TEMPERATURE 4387 03:20:06,280 --> 03:20:08,400 BETWEEN NOT SEVERE CRS AND 4388 03:20:08,400 --> 03:20:11,400 SEVERE CRS AND NO LONGER SAW 4389 03:20:11,400 --> 03:20:12,680 DIFFERENCE IN TEMPERATURE AND 4390 03:20:12,680 --> 03:20:14,800 PATIENTS THAT WENT ON TO HAVE 4391 03:20:14,800 --> 03:20:16,520 SEVERE CRS AND THOSE THAT DIDN'T 4392 03:20:16,520 --> 03:20:20,360 AND BOTTOM DLT COHORT WE WERE 4393 03:20:20,360 --> 03:20:23,360 INTERVENING WITH PATIENTS WITH 4394 03:20:23,360 --> 03:20:26,000 -- INTERVENING FOR MILD CRS THAT 4395 03:20:26,000 --> 03:20:28,000 IS DESCRIPTIVE AND NOT POWERED 4396 03:20:28,000 --> 03:20:30,560 AND WE SAW A DROP IN RATE OF 4397 03:20:30,560 --> 03:20:33,840 SEVERE CRS FROM 30 TO 15% AND 4398 03:20:33,840 --> 03:20:34,880 IMPORTANTLY SAW NO DIFFERENCE 4399 03:20:34,880 --> 03:20:36,640 AND IMPORTANTLY FOR MANY REASONS 4400 03:20:36,640 --> 03:20:39,760 WE SAW NO DITCHES IN SEVERE 4401 03:20:39,760 --> 03:20:41,080 NEUROTOXICITY WE WERE NOT MAKING 4402 03:20:41,080 --> 03:20:44,280 IT WORSE AT SAME TIME 4403 03:20:44,280 --> 03:20:45,680 INTERVENING TOES SEE AND 4404 03:20:45,680 --> 03:20:49,320 STEROIDS IS NOT IMPACTING IN A 4405 03:20:49,320 --> 03:20:52,000 GOOD WAY THE NEUROTOXICITY AND 4406 03:20:52,000 --> 03:20:57,760 SAW NO IMPACT ON -- 4407 03:20:57,760 --> 03:21:01,120 >> ANTIGEN RECEPTOR. 4408 03:21:01,120 --> 03:21:02,920 >> THANK YOU, KRYSTAL. 4409 03:21:02,920 --> 03:21:03,440 >> [LAUGHING]. 4410 03:21:03,440 --> 03:21:05,240 >> AS WE WERE DOING THIS OTHER 4411 03:21:05,240 --> 03:21:07,120 GROUPS STARTED TO DO THIS AS 4412 03:21:07,120 --> 03:21:09,840 WELL AND HAVING LESS CONCERN 4413 03:21:09,840 --> 03:21:11,880 ABOUT EARLIER INTERVENTION AND I 4414 03:21:11,880 --> 03:21:13,520 DIDN'T SAY THAT IN THE BEGINNING 4415 03:21:13,520 --> 03:21:16,680 NOBODY WANT THE TO TAKE AWAY 4416 03:21:16,680 --> 03:21:19,440 EFFICACY OF CARS AND WE LET 4417 03:21:19,440 --> 03:21:21,920 PATIENTS GET VERY SICK AND CHOC 4418 03:21:21,920 --> 03:21:24,840 WENT ON TO DO AN EARLY STUDY OF 4419 03:21:24,840 --> 03:21:28,280 IT IN EARLY COHORT AND 4420 03:21:28,280 --> 03:21:30,560 PERSISTENT FEVER AND TWO 4421 03:21:30,560 --> 03:21:32,480 TEMPERATURES MEASURED 4 HOURS 4422 03:21:32,480 --> 03:21:34,440 APART AND THEY COMPARED THIS TO 4423 03:21:34,440 --> 03:21:36,080 AN INITIAL COHORT. 4424 03:21:36,080 --> 03:21:38,120 AND THEY WERE SAYING IT WOULD BE 4425 03:21:38,120 --> 03:21:40,960 SUCCESS IF LESS THAN OR EQUAL TO 4426 03:21:40,960 --> 03:21:48,160 5 OF 15 HIGH REGARDING PAIENTS 4427 03:21:48,160 --> 03:21:49,480 PATIENTS WENT ON TO DEVELOP 4428 03:21:49,480 --> 03:21:52,360 GRADE FOR CRS. THAT WAS 4429 03:21:52,360 --> 03:21:54,520 MEASURED AS A SUCCESS AND 4430 03:21:54,520 --> 03:21:57,600 HISTORIC PHASE 1 CONTROL HAD 51% 4431 03:21:57,600 --> 03:21:59,440 RATE OF GRADE 4 AND SUGING THAT 4432 03:21:59,440 --> 03:22:06,400 IT WAS PREVENTING SEVERE CRSS. 4433 03:22:06,400 --> 03:22:09,800 RECENTLY THIS IS FROM SDVMENT 4434 03:22:09,800 --> 03:22:11,200 UMA1 AND THIS CELL POPULATION 4435 03:22:11,200 --> 03:22:13,800 AND THERE IS A LOT OF COHORTS ON 4436 03:22:13,800 --> 03:22:15,040 SDOOUMA. I DIDN'T PARTICIPATE 4437 03:22:15,040 --> 03:22:17,240 IN IT AND GET CONFUSE THE AND 4438 03:22:17,240 --> 03:22:21,080 COHORT 6 IS ONE THEY LOOKED AT 4439 03:22:21,080 --> 03:22:23,360 PROPHYLACTIC STEROIDS AND IDEA 4440 03:22:23,360 --> 03:22:28,080 IS PATIENTS GET 10 MILLIGRAMS ON 4441 03:22:28,080 --> 03:22:32,360 DAY 0 AND DAY 1 AND DAY 2 AND 4442 03:22:32,360 --> 03:22:38,600 THREE DAYS ARROW AND AT TOP 4443 03:22:38,600 --> 03:22:41,440 ORIGINAL STRATEGY AND PATIENTS 4444 03:22:41,440 --> 03:22:45,520 WERE NOT GETTING TOSIE OR 4445 03:22:45,520 --> 03:22:48,240 STEROIDS WELL UNTIL THEY WERE IN 4446 03:22:48,240 --> 03:22:52,200 GRADE 2 AND 4 AND COHORT 6 4447 03:22:52,200 --> 03:22:54,400 INTERVENING EARLIER AT CRS FOR 4448 03:22:54,400 --> 03:22:57,160 GRADE 1 AND INITIAL TWO COHORTS 4449 03:22:57,160 --> 03:22:59,520 SEVERE CRS RATE WAS THEIR TA EN% 4450 03:22:59,520 --> 03:23:01,800 THAT IS BASED ON LEAD CRITERIA 4451 03:23:01,800 --> 03:23:09,160 OF GRADING AND SEVERE CRS COHORT 4452 03:23:09,160 --> 03:23:10,800 INTERVENTION WITH THIS 4453 03:23:10,800 --> 03:23:11,600 PROPHYLACTICALLY. HOST WOULD 4454 03:23:11,600 --> 03:23:17,360 LIKE TO UNMUTE ME. STAY MUTED. 4455 03:23:17,360 --> 03:23:21,440 SEVERE CRS DROPPED FROM 13 TO 0% 4456 03:23:21,440 --> 03:23:23,240 THAT IS DESCRIPTIVE NOT 4457 03:23:23,240 --> 03:23:24,920 STATISTICALLY POWERED AND THEY 4458 03:23:24,920 --> 03:23:28,440 NOTICED CRS OCCURRED IN 80% OF 4459 03:23:28,440 --> 03:23:30,080 PATIENTS ALL GRADE 1 AND 2 AND 4460 03:23:30,080 --> 03:23:33,080 ALL RESOLVED AND MEDIAN TIME TO 4461 03:23:33,080 --> 03:23:35,560 ONSET CRS WAS 5 DAYS WITH 4462 03:23:35,560 --> 03:23:37,320 DURATION OF 4 DAYS AND COMPARE 4463 03:23:37,320 --> 03:23:40,720 TODAY COHORT 1 AND 2 DELAYED ON 4464 03:23:40,720 --> 03:23:43,200 SET OF CRS AND DURATION AND 4465 03:23:43,200 --> 03:23:44,880 IMPORTANT FACT INTERVENING EARLY 4466 03:23:44,880 --> 03:23:48,280 WITH STEROIDS 7 TAEN% OF 4467 03:23:48,280 --> 03:23:50,560 PATIENTS RECEIVED STEROIDS FOR 4468 03:23:50,560 --> 03:23:52,320 TREATMENT RATHER THAN 4469 03:23:52,320 --> 03:23:53,640 PROPHYLAXIS AND DOSE THAT WAS 4470 03:23:53,640 --> 03:23:55,800 GIVEN IN COHORT 1 AND 2 WAS 4471 03:23:55,800 --> 03:23:58,000 HIGHER AND COHORT 1 AND 2 4472 03:23:58,000 --> 03:24:00,960 CUMULATIVE DOSE OF STEROIDS WAS 4473 03:24:00,960 --> 03:24:05,280 THIS VERSUS 1800 IN COHORT 6 AND 4474 03:24:05,280 --> 03:24:06,920 INTERVENING EARLY YOU CAN 4475 03:24:06,920 --> 03:24:09,440 PREVENT CRS AND OVERALL GIVE 4476 03:24:09,440 --> 03:24:11,280 LESS STEROIDS AND INTERESTING 4477 03:24:11,280 --> 03:24:14,040 THING HERE DESCRIPTIVELY IS 4478 03:24:14,040 --> 03:24:18,440 PATIENTS HAD IMPROVED EFFICACY 4479 03:24:18,440 --> 03:24:23,200 FROM AXIES CELL. 4480 03:24:23,200 --> 03:24:26,840 SO TOSIE AND STEROIDS WERE GREAT 4481 03:24:26,840 --> 03:24:29,120 TO GET US STARTED AND WE SHOULD 4482 03:24:29,120 --> 03:24:31,120 HEAD NOW AND BE MORE PRECISE AND 4483 03:24:31,120 --> 03:24:33,720 LIKE THIS DIAGRAM THAT IS 4484 03:24:33,720 --> 03:24:34,760 CONTEMPORARY OVERVIEW OF 4485 03:24:34,760 --> 03:24:37,360 PATHOLOGY OF CRS THAT OBVIOUSLY 4486 03:24:37,360 --> 03:24:41,120 IS MULTIFACTORIAL AND YOU ARE 4487 03:24:41,120 --> 03:24:42,320 ENGAGING CAR T-CELL WITH TUMOR 4488 03:24:42,320 --> 03:24:44,560 AND RECRUITING PARTS OF THE 4489 03:24:44,560 --> 03:24:48,160 IMMUNE SYSTEM AND MONOCITES PLAY 4490 03:24:48,160 --> 03:24:52,240 A BIG ROLE IN CRS AND THERE IS 4491 03:24:52,240 --> 03:24:56,600 AISLE 1 TO AISLE 6 CREATING 4492 03:24:56,600 --> 03:24:59,160 CYTOKINE CASCADE AND SYNDROME IN 4493 03:24:59,160 --> 03:25:01,800 ORGAN TOXICITY YOU SEE AND 4494 03:25:01,800 --> 03:25:03,400 CORRELATED WITH ENGRAPHMENT AND 4495 03:25:03,400 --> 03:25:07,880 HAVE DIFFERENTIATING PEEKS WITH 4496 03:25:07,880 --> 03:25:09,280 ICANS RELATED TO DIFFERENTIAL 4497 03:25:09,280 --> 03:25:10,680 EXPRESSION OF CYTOKINES AS WELL 4498 03:25:10,680 --> 03:25:13,520 AND THIS IS A STUDY PUBLISHED 6 4499 03:25:13,520 --> 03:25:16,240 OR 5 YEARS AGO NOW LOOKING AT 4500 03:25:16,240 --> 03:25:18,920 MOUSE MODEL AT ROLE OF MONOCITES 4501 03:25:18,920 --> 03:25:21,040 DRIVING IN CRS AND THOSE THAT 4502 03:25:21,040 --> 03:25:23,720 HAVE NOT READ THIS PAPER I 4503 03:25:23,720 --> 03:25:25,040 RECOMMEND GOING THROUGH LOOKING 4504 03:25:25,040 --> 03:25:29,040 AT PAPER IN ENTIRETY AND IF YOU 4505 03:25:29,040 --> 03:25:30,600 DEPLETED MONOCITES YOU ARE ABLE 4506 03:25:30,600 --> 03:25:32,720 TO HAVE LONG-TERM SURVIVAL AND 4507 03:25:32,720 --> 03:25:34,920 HAVING MONOCITES IN THERE YOU 4508 03:25:34,920 --> 03:25:38,640 HAVE MORTALITY FROM CRS. THIS 4509 03:25:38,640 --> 03:25:41,120 REALLY LED TO SOME INCLINATION 4510 03:25:41,120 --> 03:25:44,000 THAT ANAKINRA WOULD BE HELPFUL 4511 03:25:44,000 --> 03:25:47,320 IN MANAGEMENT OF CRS THAT THERE 4512 03:25:47,320 --> 03:25:48,920 HAVE BEEN SEVERAL SMALL 4513 03:25:48,920 --> 03:25:49,920 INVESTIGATED INITIATIVE TRIALS 4514 03:25:49,920 --> 03:25:51,720 IT THAT HAVE BEEN TALKED ABOUT 4515 03:25:51,720 --> 03:25:54,040 AT VARIOUS MEETINGS OVER THE 4516 03:25:54,040 --> 03:25:56,040 LAST COUPLE OF YEARS AND THIS IS 4517 03:25:56,040 --> 03:25:59,440 TWO OF THEM AND ONE IS FROM 4518 03:25:59,440 --> 03:26:00,920 KETERRING AND B CELL PATIENTS 4519 03:26:00,920 --> 03:26:02,520 AND THEY LOOKED AND SAID YOU CAN 4520 03:26:02,520 --> 03:26:07,040 GET 100 MILLIGRAM SUBCUTANEOUS 4521 03:26:07,040 --> 03:26:11,840 HOURS ON DAY 2 AND PROPHYLACTIC 4522 03:26:11,840 --> 03:26:15,320 SETTING IN TWO FEVERS AND 74% 4523 03:26:15,320 --> 03:26:18,440 RATE CRS AND LOW RATES OF GRADE 4524 03:26:18,440 --> 03:26:23,960 3 AND 4 AND 20% OF ICANS MOSTLY 4525 03:26:23,960 --> 03:26:25,720 LOW GRADE OR NO GRADE 3 OR 5 AND 4526 03:26:25,720 --> 03:26:27,960 WHAT IS FASCINATING ABOUT KINN 4527 03:26:27,960 --> 03:26:31,920 RA IS EFFECTIVE FOR CRS AND 4528 03:26:31,920 --> 03:26:34,480 ICANS WE FEEL LIKE TOESO LUS 4529 03:26:34,480 --> 03:26:36,880 MAED IS NOT EFFECTIVE WITH ICANS 4530 03:26:36,880 --> 03:26:40,800 AND PATIENTS WERE GETTING TOE 4531 03:26:40,800 --> 03:26:42,720 SEE AND COURTI CO STEROIDS AND 4532 03:26:42,720 --> 03:26:46,920 THAT SAME 100 TO 2 MILLIGRAMS 4533 03:26:46,920 --> 03:26:49,400 SUBIS CUTANEOUS OR 4534 03:26:49,400 --> 03:26:50,600 [INDISCERNIBLE] WAS MORE FOR 4535 03:26:50,600 --> 03:26:53,600 TREATMENT REFRACTORY CRS ANY 4536 03:26:53,600 --> 03:26:56,920 CANS AND NOTED 73% OF PATIENTS 4537 03:26:56,920 --> 03:26:59,680 HAD IMPROVEMENT IN SYMPTOMS AND 4538 03:26:59,680 --> 03:27:03,280 WITH HIGH DOSE REJIMMEN AND 4539 03:27:03,280 --> 03:27:05,760 SIDENOTE THEY ARE LOGISTICALLY 4540 03:27:05,760 --> 03:27:08,640 CHALLENGING AND IS EXPENSIVE AND 4541 03:27:08,640 --> 03:27:11,520 SOBI IS ENGAGED INITIALLY 4542 03:27:11,520 --> 03:27:13,880 GETTING CRS AND ICANS AND THEY 4543 03:27:13,880 --> 03:27:16,160 BACKED AWAY FROM IT THINKING IT 4544 03:27:16,160 --> 03:27:17,880 LOGISTICALLY WOULD BE 4545 03:27:17,880 --> 03:27:19,680 CHALLENGING MOVING FORWARD WITH 4546 03:27:19,680 --> 03:27:23,240 ANAKIN IN A BIG WAY WITH 4547 03:27:23,240 --> 03:27:24,680 PROPHYLAXIS AND OTHER 4548 03:27:24,680 --> 03:27:26,160 ALTERNATIVES OUT THERE BEING 4549 03:27:26,160 --> 03:27:28,840 INVESTIGATED CLINICALLY IS 4550 03:27:28,840 --> 03:27:30,080 RAERLLY RESULTS FROM 4551 03:27:30,080 --> 03:27:34,160 [INDISCERNIBLE] AN ANTI-GMSCSF 4552 03:27:34,160 --> 03:27:36,680 ANTIBODY AND ON SDOOUMA THEY 4553 03:27:36,680 --> 03:27:41,080 LOOKED AT 6 PATIENTS AND 3 + 3 4554 03:27:41,080 --> 03:27:44,040 DESIGN DOSING PRIOR TO CAR AND 4555 03:27:44,040 --> 03:27:48,520 ADMINISTRATION OF IT REDUCED -- 4556 03:27:48,520 --> 03:27:51,600 THEY DID NOT SEE IMPACT ON 4557 03:27:51,600 --> 03:27:53,640 RESPONSES AND ALL 6 PATIENTS HAD 4558 03:27:53,640 --> 03:27:55,240 OBJECTIVE RESPONSES AND DIDN'T 4559 03:27:55,240 --> 03:27:58,600 SEE SEVERE CRS OR SEVERE I KANS 4560 03:27:58,600 --> 03:28:01,120 AND ARE WORKING ON PHASE 2 4561 03:28:01,120 --> 03:28:03,080 POTENTIAL REGISTRATION TRIAL AND 4562 03:28:03,080 --> 03:28:07,160 LYMPHOMA TO USE IN PROPHYLACTIC 4563 03:28:07,160 --> 03:28:09,000 SETTING AND YOU SEE REFERENCE OF 4564 03:28:09,000 --> 03:28:12,080 BLOOD AND EARLY PRECLINICAL DATA 4565 03:28:12,080 --> 03:28:14,040 LEADING TO INITIAL EXPLORATION 4566 03:28:14,040 --> 03:28:18,640 OF THIS AS PART OF ZUMA. 4567 03:28:18,640 --> 03:28:21,960 THEN LASTLY I THINK THIS IS ONE 4568 03:28:21,960 --> 03:28:25,200 THAT I AM MOST EXCITED ABOUT AND 4569 03:28:25,200 --> 03:28:29,680 STEVE ELUDED TO THIS EARLIER 4570 03:28:29,680 --> 03:28:33,280 TODAY INTERFERING GAMA IS A 4571 03:28:33,280 --> 03:28:35,440 CYTOKINE THAT IS QUITE ELEVATED 4572 03:28:35,440 --> 03:28:37,200 AND MIGHT BE A TRUE DRIVER. IF 4573 03:28:37,200 --> 03:28:41,240 WE CAN BLOCK INTERFERING GAMMA 4574 03:28:41,240 --> 03:28:42,640 AND POTENTIALLY WE COULD ABROW 4575 03:28:42,640 --> 03:28:46,760 GATE CRS AND DOWNSTREAM EFFECTS 4576 03:28:46,760 --> 03:28:51,400 OF THAT INCLUDING I- KANS AND 4577 03:28:51,400 --> 03:28:54,400 CARS HRH AND THIS IS A GROUP IN 4578 03:28:54,400 --> 03:28:57,960 BOSTON AND SHOWING ACTIVATION OF 4579 03:28:57,960 --> 03:28:59,840 CAR T-CELLS LEADS TO PRODUCTION 4580 03:28:59,840 --> 03:29:02,400 THAT LEADS TO MACROPHAGES AND 4581 03:29:02,400 --> 03:29:04,880 BLOCKING INTERFERING GAMMA YOU 4582 03:29:04,880 --> 03:29:08,400 CAN GO TO IMPROVED EFFICACY AND 4583 03:29:08,400 --> 03:29:11,800 DATA FROM TRIALS WITH PATIENTS 4584 03:29:11,800 --> 03:29:15,360 WITH SEVERE TOXICITY MATCH IN 4585 03:29:15,360 --> 03:29:16,680 MACHINE LEARNING WAY 4586 03:29:16,680 --> 03:29:18,040 DYSFUNCTIONAL RESPONDERS AND 4587 03:29:18,040 --> 03:29:20,000 THERE IS THOUGHT BLOCKING 4588 03:29:20,000 --> 03:29:21,920 INTERFERON GAMMA YOU WILL NOT 4589 03:29:21,920 --> 03:29:24,320 ONLY REDUCE TOXICITY BUT YOU CAN 4590 03:29:24,320 --> 03:29:26,520 IMPROVE EFFICACY AND ON BOTTOM 4591 03:29:26,520 --> 03:29:29,520 HERE YOU CAN SEE COMPARING GAMMA 4592 03:29:29,520 --> 03:29:37,360 WITH ANAKIN RA AND TOE SEW LUSA 4593 03:29:37,360 --> 03:29:42,760 MAB CYTOKINES IN COMPARISON TO 4594 03:29:42,760 --> 03:29:44,960 BLOCKING AISLE 1 AND RECEPTOR 4595 03:29:44,960 --> 03:29:47,320 BLOCKADE AND THIS IS EXCITING 4596 03:29:47,320 --> 03:29:49,600 AND SOBI SEEMS TO BE MORE 4597 03:29:49,600 --> 03:29:53,440 ENGAGED NOW USING GAMMA IN 4598 03:29:53,440 --> 03:29:55,160 PROPHYLACTIC SETTING IN CAR 4599 03:29:55,160 --> 03:29:57,120 T-CELLS AND INVESTIGATOR 4600 03:29:57,120 --> 03:29:58,960 INITIATED TRIALS COME OUT IN THE 4601 03:29:58,960 --> 03:30:01,040 NEXT YEAR TO INVESTIGATE THIS 4602 03:30:01,040 --> 03:30:02,600 CLINICALLY AND ONE THING THAT IS 4603 03:30:02,600 --> 03:30:05,360 IMPORTANT MOVING LATER IN THE 4604 03:30:05,360 --> 03:30:07,840 DAY TALKING ABOUT SOLID TUMORS 4605 03:30:07,840 --> 03:30:09,480 BLOCKING INTERFERON GAMMA IN 4606 03:30:09,480 --> 03:30:11,480 TUMORS IN PROPHYLACTIC SETTING 4607 03:30:11,480 --> 03:30:13,400 IT IS CRITICAL FOR TUMOR KILLING 4608 03:30:13,400 --> 03:30:15,760 IN SOLID TUMORS AND WOULD BE 4609 03:30:15,760 --> 03:30:23,560 SPECIFIC TO LIQUID TUMORS. 4610 03:30:23,560 --> 03:30:25,440 MOVING FORWARD QUESTIONS TO ASK 4611 03:30:25,440 --> 03:30:28,280 OURSELVES IS HOW TO PRIORITIZE 4612 03:30:28,280 --> 03:30:30,240 AGENTS TO INVESTIGATE AND 4613 03:30:30,240 --> 03:30:32,840 DECIDING WHEN TO INTERVENE AND 4614 03:30:32,840 --> 03:30:35,840 DECIDE WHAT OPTIMAL THERAPY IS 4615 03:30:35,840 --> 03:30:42,160 FOR PREVENTION AND TREATMENT AND 4616 03:30:42,160 --> 03:30:54,520 WITH THAT I WILL SIT DOWN. 4617 03:30:54,520 --> 03:31:02,760 >> WE WILL GET INTO THE NEXT 4618 03:31:02,760 --> 03:31:05,520 TALK. I HAVE BEEN TASKED WITH 4619 03:31:05,520 --> 03:31:07,520 DISCUSSING PRE-EMPTIVE 4620 03:31:07,520 --> 03:31:09,880 STRATEGIES AND MANAGEMENT 4621 03:31:09,880 --> 03:31:12,200 STRATEGIES ANY CANS THERAPY AND 4622 03:31:12,200 --> 03:31:18,960 I HAVE NO DISCLOSURES. AS YOU 4623 03:31:18,960 --> 03:31:22,680 KNOW IN PIVOTAL STUDIES NO 4624 03:31:22,680 --> 03:31:25,320 UNIFORM GRADING EXISTED TALKING 4625 03:31:25,320 --> 03:31:28,240 ABOUT TOXICITY IN T-CELL THERAPY 4626 03:31:28,240 --> 03:31:30,800 AND ACROSS TRIALS EVALUATING 4627 03:31:30,800 --> 03:31:33,680 SUBJECTS EFFECTIVELY TO HAVE 4628 03:31:33,680 --> 03:31:34,320 REPRODUCIBILITY AND 4629 03:31:34,320 --> 03:31:37,720 COMPARABILITY AND WHAT WE NEEDED 4630 03:31:37,720 --> 03:31:40,480 WAS TO HAVE TESTS OR TESTING TO 4631 03:31:40,480 --> 03:31:42,600 EASILY ADMINISTER ALLOWING FOR 4632 03:31:42,600 --> 03:31:45,160 RAPID AND DYNAMIC ASSESSMENTS 4633 03:31:45,160 --> 03:31:49,560 AND AS SUCH ASTCT LIKE CRS 4634 03:31:49,560 --> 03:31:52,240 CREATED CONSENSUS UNIFORM 4635 03:31:52,240 --> 03:31:55,280 GRADING SYSTEM TERMS ICANS AND 4636 03:31:55,280 --> 03:31:58,400 IT INCLUDES COMPOSITE SCORE OF 4637 03:31:58,400 --> 03:32:00,440 ENCEPHALOPATHY SCALES THAT IS 4638 03:32:00,440 --> 03:32:02,600 BASED ON AGE AND SCIENCE AND 4639 03:32:02,600 --> 03:32:04,280 SYMPTOMS OF FOUR GLOBAL DOMAINS 4640 03:32:04,280 --> 03:32:06,000 INCLUDING LEVEL OF CONSCIOUSNESS 4641 03:32:06,000 --> 03:32:10,120 AND SEIZURES AND MOTOR WEAKNESS 4642 03:32:10,120 --> 03:32:13,320 AND NOTABLY SYMPTOMS EXCLUDED 4643 03:32:13,320 --> 03:32:16,600 FROM ICANS INCLUDE HEADACHE 4644 03:32:16,600 --> 03:32:19,440 TREMORS WEAKNESS HALLUCINATIONS 4645 03:32:19,440 --> 03:32:26,480 AND INTERCRANIAL HEMORRHAGE. IN 4646 03:32:26,480 --> 03:32:28,080 PIVOTAL PEDIATRIC TRIALS THERE 4647 03:32:28,080 --> 03:32:31,280 ARE VARYING RATES OF SEVERE 4648 03:32:31,280 --> 03:32:32,760 NEUROTOXICITY AND WE DISCUSSED 4649 03:32:32,760 --> 03:32:35,160 NO UNIFORM GRADING ACROSS TRIALS 4650 03:32:35,160 --> 03:32:38,040 AND ADVERSE EVENTS DIFFERED IN 4651 03:32:38,040 --> 03:32:39,480 DESCRIPTIONS AND DEFINITIONS 4652 03:32:39,480 --> 03:32:42,440 THAT IS NOT COMPARABLE. THERE 4653 03:32:42,440 --> 03:32:44,720 ARE SEVERAL SPECIFIC AND 4654 03:32:44,720 --> 03:32:45,960 PEDIATRIC CONSIDERATIONS NEEDING 4655 03:32:45,960 --> 03:32:48,320 TO BE TAKEN WHEN DISCUSSING 4656 03:32:48,320 --> 03:32:49,800 ICANN AND CURRENT TREATMENT 4657 03:32:49,800 --> 03:32:52,200 PARADIGM ASSESSING NEUROTOXICITY 4658 03:32:52,200 --> 03:32:55,800 RELIES ON LANGUAGE AND MOTOR 4659 03:32:55,800 --> 03:32:56,880 SKILLS CHILDREN MIGHT NOT HAVE 4660 03:32:56,880 --> 03:32:58,680 DEPENDING ON AGE AND 4661 03:32:58,680 --> 03:32:59,520 ADDITIONALLY IS IMPORTANT TO 4662 03:32:59,520 --> 03:33:02,400 NOTE THAT THEY ARE CAPTIVE 4663 03:33:02,400 --> 03:33:05,160 RECOGNIZING DELL EARIUM IN ICU 4664 03:33:05,160 --> 03:33:08,320 SETTINGS AND IS NOT VALIDATED IN 4665 03:33:08,320 --> 03:33:09,520 INPATIENT AND OUTPATIENT 4666 03:33:09,520 --> 03:33:11,640 SETTINGS AND WHAT WE USE IT 4667 03:33:11,640 --> 03:33:14,360 FORMILD TOXICITY MAY MANIFEST 4668 03:33:14,360 --> 03:33:19,160 SUBTLE BEHAVIORAL CHANGES NOTING 4669 03:33:19,160 --> 03:33:20,600 CAREGIVERS WITH PATIENTS AND 4670 03:33:20,600 --> 03:33:22,640 NEUR LOGIC EXAM COULD BE 4671 03:33:22,640 --> 03:33:24,160 DIFFICULT IN CHILDREN THAT ARE 4672 03:33:24,160 --> 03:33:26,240 HEALTHY AND COMPOUND WITH 4673 03:33:26,240 --> 03:33:27,560 PATIENTS RECEIVING CAR T-CELL 4674 03:33:27,560 --> 03:33:29,880 THERAPY AND ARE ASKING PATIENTS 4675 03:33:29,880 --> 03:33:32,960 WITH REGARDS TO COOPERATION AND 4676 03:33:32,960 --> 03:33:34,480 PARTICIPATION TO OBTAIN MOST 4677 03:33:34,480 --> 03:33:37,560 EXCELLENT NEUROEXAM WE CAN. 4678 03:33:37,560 --> 03:33:38,720 PATIENT DEPENDENT FACTORS 4679 03:33:38,720 --> 03:33:40,600 INCLUDE ABILITY TO TOLERATE MRIS 4680 03:33:40,600 --> 03:33:46,360 AND EEGS WITHOUT PUNCTURES OR 4681 03:33:46,360 --> 03:33:48,280 ANTHEESHA AND IF THEY CAN'T DO 4682 03:33:48,280 --> 03:33:50,480 IT IT COULD DELAY DIAGNOSIS AND 4683 03:33:50,480 --> 03:33:53,040 COURSE OF THE DAY AND COMMON 4684 03:33:53,040 --> 03:33:55,880 SYMPTOMS OF ICANS INCLUDES 4685 03:33:55,880 --> 03:33:57,320 DLEERIUM AND LANGUAGE 4686 03:33:57,320 --> 03:33:59,400 DISTURBANCES AND CONFUSION AND 4687 03:33:59,400 --> 03:34:02,520 ALTERED MENTAL STATUS WITH 4688 03:34:02,520 --> 03:34:04,880 CONCEPTS BEING FOCAL DEFICITS 4689 03:34:04,880 --> 03:34:08,280 AND EDEMA IN PEDIATRIC 4690 03:34:08,280 --> 03:34:10,760 POPULATION AND DEMONSTRATING IN 4691 03:34:10,760 --> 03:34:12,520 SCHEMATIC IT PROCEEDS ICANS AND 4692 03:34:12,520 --> 03:34:14,440 THEY HAVE TEMPORAL OVERLAP AND 4693 03:34:14,440 --> 03:34:16,440 TALK WILL HAVE LOTS OF OVERLAP 4694 03:34:16,440 --> 03:34:19,680 AS WELL. THANKFULLY IN 4695 03:34:19,680 --> 03:34:23,400 PEDIATRICS ICANS IS REVERSIBLE 4696 03:34:23,400 --> 03:34:24,080 AND SELF-LIMITED TREATMENT 4697 03:34:24,080 --> 03:34:26,400 APPROACH IS BASED ON SEVERITY 4698 03:34:26,400 --> 03:34:31,120 AND SYMPTOMS PRESENT AND TO DATE 4699 03:34:31,120 --> 03:34:38,280 COURTI CO STEROIDS EXIST -- AREA 4700 03:34:38,280 --> 03:34:41,240 OF ACTIVE INVESTIGATION INCLUDES 4701 03:34:41,240 --> 03:34:42,840 SUPPORTIVE CARE AND PREVENTION 4702 03:34:42,840 --> 03:34:45,440 STRATEGIES METHODS AND CURRENT 4703 03:34:45,440 --> 03:34:46,640 PRACTICES FOR PREVENTION 4704 03:34:46,640 --> 03:34:50,640 STRATEGIES ARE ANTISEIZURE 4705 03:34:50,640 --> 03:34:54,080 PROPHYLAXIS AND SCHEMATIC PUT 4706 03:34:54,080 --> 03:34:57,600 FORTH IN REVIEW PAPER SIMILAR TO 4707 03:34:57,600 --> 03:35:00,200 CRS ICANS PREVENTION STRATEGIES 4708 03:35:00,200 --> 03:35:02,600 ARE TARGETING INFLAMMATORY 4709 03:35:02,600 --> 03:35:05,080 CYTOKINES AND BY ACTIVATION OF 4710 03:35:05,080 --> 03:35:08,000 CAR T-CELLS BINDING TUMOR 4711 03:35:08,000 --> 03:35:11,520 ANTIGENS RESULTS IN 4712 03:35:11,520 --> 03:35:14,480 PROINFLAMMATORY CYTOKINE CASCADE 4713 03:35:14,480 --> 03:35:18,520 LEADING TO ACTIVATION THAT IN 4714 03:35:18,520 --> 03:35:20,560 TURN CONTINUES CASCADE WITH 4715 03:35:20,560 --> 03:35:23,320 AISLE 1 AND NITRIC OXIDE AND 4716 03:35:23,320 --> 03:35:24,800 THERE IS SIGNIFICANT PRECLINICAL 4717 03:35:24,800 --> 03:35:27,680 DATA SHOWING PROMISING RESULTS 4718 03:35:27,680 --> 03:35:30,440 USING SEVERAL BYLOGIC AGENTS TO 4719 03:35:30,440 --> 03:35:33,440 TREAT AND PREVENT CRS ICANS. WE 4720 03:35:33,440 --> 03:35:34,840 HEARD THERE IS SEVERAL PHASE 1 4721 03:35:34,840 --> 03:35:38,000 AND 2 STUDIES PUT FORTH IN ADULT 4722 03:35:38,000 --> 03:35:39,720 LITERATURE DEMONSTRATING 4723 03:35:39,720 --> 03:35:42,600 FEASIBILITY SAFETY AND EFFICACY 4724 03:35:42,600 --> 03:35:50,120 USING BUY LOGIC AGENTS TO REDUCE 4725 03:35:50,120 --> 03:35:52,680 CRS IN ICANS. 4726 03:35:52,680 --> 03:35:55,160 INTEGRAL PART SEEN AS 4727 03:35:55,160 --> 03:35:57,200 PROPHYLAXIS IN PEDIATRIC ALL 4728 03:35:57,200 --> 03:36:02,000 THERAPY PARADIGM UTILIZATION OF 4729 03:36:02,000 --> 03:36:03,800 ANL-BASED CHILDREN'S ONCOLOGY 4730 03:36:03,800 --> 03:36:05,400 GROUP HAS DEMONSTRATED 4731 03:36:05,400 --> 03:36:08,440 FEASIBILITY AND EFFECTIVENESS IN 4732 03:36:08,440 --> 03:36:13,360 TREATMENT FOR ICANS IN NIH AND 4733 03:36:13,360 --> 03:36:15,760 PEDIATRIC ONCOLOGY BADGE AND 4734 03:36:15,760 --> 03:36:17,400 CHALLENGES REMAIN IN POPULATION 4735 03:36:17,400 --> 03:36:19,720 AND WITH PEDIATRICS YOUNG 4736 03:36:19,720 --> 03:36:23,320 PATIENTS REQUIRING ANESTHESIA 4737 03:36:23,320 --> 03:36:26,720 AND DEPENDENT ON CAR CONSTRUCT 4738 03:36:26,720 --> 03:36:28,800 THEY ARE RECEIVING AND WITH 4739 03:36:28,800 --> 03:36:32,800 CEREBRAL ED EMA AND SAFE 4740 03:36:32,800 --> 03:36:35,960 PUVENGURE AND WE HAVE BEEN ABLE 4741 03:36:35,960 --> 03:36:38,680 TO UTILIZE CORTISONE AND FIVE 4742 03:36:38,680 --> 03:36:44,800 SUBJECTS WITH CD19 DIRECTED OR 4743 03:36:44,800 --> 03:36:50,160 CD19-22 DIRECTED CAR T-CELLS OR 4744 03:36:50,160 --> 03:36:52,000 WORSENING SYMPTOMOLOGY DESPITE 4745 03:36:52,000 --> 03:36:56,400 USE OF SYSTEMIC HYDRO STEROIDS 4746 03:36:56,400 --> 03:36:58,960 THERE IS RAPID SYMPTOMS WITHIN 4747 03:36:58,960 --> 03:37:03,280 24 HOURS OF ADMINISTRATION OF 4748 03:37:03,280 --> 03:37:05,600 CORTISONE WE ARE ABLE TO 4749 03:37:05,600 --> 03:37:08,160 FACILITATE RAPID SYSTEMIC 4750 03:37:08,160 --> 03:37:10,040 [INDISCERNIBLE] AND NOTABLY ABLE 4751 03:37:10,040 --> 03:37:12,560 TO DEMONSTRATE CAR T-CELL 4752 03:37:12,560 --> 03:37:14,880 PERSISTENCE IN CSF IS UNCHANGED 4753 03:37:14,880 --> 03:37:19,440 IN COMPARING PATIENTS RECEIVING 4754 03:37:19,440 --> 03:37:20,320 HYDROCORTISONE VERSUS THOSE THAT 4755 03:37:20,320 --> 03:37:22,080 RECEIVED STANDARD OF CARE THAT 4756 03:37:22,080 --> 03:37:24,360 INCLUDED PATIENTS RECEIVING HIGH 4757 03:37:24,360 --> 03:37:26,800 DOSE SYSTEMIC STEROIDS AND SO IN 4758 03:37:26,800 --> 03:37:28,280 THIS GRAPH THAT YOU SEE TO THE 4759 03:37:28,280 --> 03:37:30,560 RIGHT OF THE SCREEN, PERCENTAGE 4760 03:37:30,560 --> 03:37:33,680 OF T-CELLS POSITIVE FOR CAR IN 4761 03:37:33,680 --> 03:37:37,320 CSF, IT IS AS COMPARED TO THE 4762 03:37:37,320 --> 03:37:38,720 GROUP VERSUS STANDARD OF CARE 4763 03:37:38,720 --> 03:37:41,640 GROUP DEMONSTRATES GROUPS HAVE 4764 03:37:41,640 --> 03:37:44,760 CAR T-CELL PERSISTENCE AT DAY 28 4765 03:37:44,760 --> 03:37:49,920 AND THUS INTRATHECAL 4766 03:37:49,920 --> 03:37:52,600 HYDROCORTISONE -- ICANS AS 4767 03:37:52,600 --> 03:37:55,160 PRE-EMPTIVE STRATEGY TO PREVENT 4768 03:37:55,160 --> 03:37:57,320 GRADE 4 ICANS AND MOST PATIENTS 4769 03:37:57,320 --> 03:38:00,280 WILL HAVE EVOLVED TO SEVERE 4770 03:38:00,280 --> 03:38:03,000 ICANS WHILE ON SYSTEMIC STEROIDS 4771 03:38:03,000 --> 03:38:08,120 AND SEVERAL ADULT CASE RESUPORT 4772 03:38:08,120 --> 03:38:10,760 HAVE BEEN PUBLISHED PLUS OR 4773 03:38:10,760 --> 03:38:13,960 MINUS CHEMOTHERAPY AND TREATING 4774 03:38:13,960 --> 03:38:17,240 STEROID REFRACTORY ICANS AND 4775 03:38:17,240 --> 03:38:22,200 PAPER PUBLISHED IS DEMONSTRATED 4776 03:38:22,200 --> 03:38:24,840 INTRATHECAL THERAPY WITH 4777 03:38:24,840 --> 03:38:26,640 HYDROCORTISONE -- IMPROVED 4778 03:38:26,640 --> 03:38:28,840 PROGRESSION FREE SURVIVAL AND 4779 03:38:28,840 --> 03:38:31,280 OVERALL SURVIVAL IN THOSE THAT 4780 03:38:31,280 --> 03:38:33,920 RECEIVE THERAPY AND ADDITIONALLY 4781 03:38:33,920 --> 03:38:36,320 LOWER MEDIAN CUMULATIVE DOSE OF 4782 03:38:36,320 --> 03:38:40,840 SYSTEMIC STEROIDS USED. 4783 03:38:40,840 --> 03:38:43,560 USE IN PEDIATRIC PATIENTS WITH 4784 03:38:43,560 --> 03:38:46,480 T-CELL TOXICITIES IS PUBLISHED 4785 03:38:46,480 --> 03:38:48,000 BY SEVERAL CENTERS PRESENT HERE 4786 03:38:48,000 --> 03:38:50,800 TODAY MULTICENTER RETROSPECTIVE 4787 03:38:50,800 --> 03:38:53,000 STUDY EVALUATING INDICATIONS 4788 03:38:53,000 --> 03:38:54,440 TIMING OF ADMINISTRATION AND 4789 03:38:54,440 --> 03:38:58,720 DOSING FOR ANAKIN RA AND MOST 4790 03:38:58,720 --> 03:39:09,280 FROO EBBING WENT INDICATIONS -- 4791 03:39:18,520 --> 03:39:22,840 AS DEMONSTRATED EARLIER ANAKIN 4792 03:39:22,840 --> 03:39:25,800 RIN TREATMENT FOR ICANS ADULTS 4793 03:39:25,800 --> 03:39:28,640 BENEFIT IN MOST REPORTS AND I 4794 03:39:28,640 --> 03:39:29,840 WILL SKIP THROUGH SLIDE FOR SAKE 4795 03:39:29,840 --> 03:39:34,720 OF TIME. DATA WAS PRESENTED 4796 03:39:34,720 --> 03:39:37,840 ALTERNATIVE TREATMENT OPTIONS 4797 03:39:37,840 --> 03:39:39,560 INCLUDE MONO CLONAL ANTIBODY AND 4798 03:39:39,560 --> 03:39:42,280 WILL SAY THERE IS NO DATA IN 4799 03:39:42,280 --> 03:39:44,520 TREATMENT FOR ICANS IN PEDIATRIC 4800 03:39:44,520 --> 03:39:46,720 POPULATION AND THERE IS EMERGING 4801 03:39:46,720 --> 03:39:48,720 DATA AND POOR TOXIN OF USE IN 4802 03:39:48,720 --> 03:39:50,640 FIRST LINE THERAPY THAT WAS 4803 03:39:50,640 --> 03:39:54,600 RECENTLY PRESENTED AT TCT THIS 4804 03:39:54,600 --> 03:40:04,840 PAST YEAR. 4805 03:40:11,240 --> 03:40:13,040 AS WE MOVE FORWARD INTO THE 4806 03:40:13,040 --> 03:40:16,960 WORLD IT IS IMPORTANT TO NOTE 4807 03:40:16,960 --> 03:40:22,320 NOT ALL NEUROTOXICITIES ARE 4808 03:40:22,320 --> 03:40:27,600 EQUAL WHAT WE KNOW SO FAR IS 4809 03:40:27,600 --> 03:40:31,480 ENDOTHELIAL ACTIVATIONS ARE 4810 03:40:31,480 --> 03:40:35,920 IMPLEMENTED AND CD22 CAR T-CELL 4811 03:40:35,920 --> 03:40:39,640 TRIAL ENDOTHELIAL ACTIVATION AND 4812 03:40:39,640 --> 03:40:41,320 DISRUPTION CITY DIDN'T SEE 4813 03:40:41,320 --> 03:40:43,240 CORRELATIONS WITH HIGH LEVELS OF 4814 03:40:43,240 --> 03:40:44,680 NEUROTOXICITY AND WHEN LOOKING 4815 03:40:44,680 --> 03:40:47,200 AT SINGLE CELL RNA EXPRESSION 4816 03:40:47,200 --> 03:40:49,320 OVER THREE DATABASES WE DIDN'T 4817 03:40:49,320 --> 03:40:52,840 SEE CD22 EXPRESSION DEMONSTRATED 4818 03:40:52,840 --> 03:40:55,240 IN NEUROVASCULAR CELLS AND 4819 03:40:55,240 --> 03:40:58,200 HYPOTHESIS COULD BE DIFFERENTIAL 4820 03:40:58,200 --> 03:41:01,040 ANTIGEN EXPRESSION IN CNS MAY 4821 03:41:01,040 --> 03:41:03,760 IMPACT CLINICAL SYMPTOMS AND 4822 03:41:03,760 --> 03:41:05,520 ADDITIONALLY MOST RECENT 4823 03:41:05,520 --> 03:41:08,000 PUBLICATION OUT OF STANFORD 4824 03:41:08,000 --> 03:41:10,520 USING GT2 CAR CELLS WITH 4825 03:41:10,520 --> 03:41:13,320 PATIENTS WITH CAR CELLS WITH 4826 03:41:13,320 --> 03:41:15,120 GLEOMAS DEMONSTRATED DIFFERENT 4827 03:41:15,120 --> 03:41:18,880 TYPE OF NEUROTOXICITY -- WHERE 4828 03:41:18,880 --> 03:41:20,440 PATIENTS DEVELOP TRANSIENT 4829 03:41:20,440 --> 03:41:22,400 WORSENING OF EXISTING DEFICITS 4830 03:41:22,400 --> 03:41:27,640 WITH EPISODES OF EDEMA AND THIS 4831 03:41:27,640 --> 03:41:29,280 IS DIFFERENT THAN ICANS 4832 03:41:29,280 --> 03:41:30,120 TRADITIONALLY AND HAVE TO KEEP 4833 03:41:30,120 --> 03:41:33,360 IT IN MIND AS WE MOVE FORWARD IN 4834 03:41:33,360 --> 03:41:35,960 THE CAR T-CELL WORLD AND CURRENT 4835 03:41:35,960 --> 03:41:38,320 APPROACH TO DIAGNOSIS AND 4836 03:41:38,320 --> 03:41:41,080 MANAGEMENT OF ICANS IS DOG 4837 03:41:41,080 --> 03:41:42,600 COMPREHENSIVE PREINFUSION 4838 03:41:42,600 --> 03:41:44,640 EVALUATION WITH BASELINE NEUR 4839 03:41:44,640 --> 03:41:49,240 LOGIC EVALUATIONS WITH 4840 03:41:49,240 --> 03:41:52,320 NEUROTESTING AND NEUROCONSULTS 4841 03:41:52,320 --> 03:41:58,040 FOR HIGH RISK PATIENTS ENGAGING 4842 03:41:58,040 --> 03:41:58,760 PROPHYLACTIC KEPPRA FOR PATIENTS 4843 03:41:58,760 --> 03:42:00,800 POST MONITORING LOOKS TO 4844 03:42:00,800 --> 03:42:03,720 ADDITIONAL INCREASED TESTING FOR 4845 03:42:03,720 --> 03:42:05,880 PATIENTS DEVELOPING CYTOKINE 4846 03:42:05,880 --> 03:42:07,760 SYNDROME OR PATIENTS GETTING CAR 4847 03:42:07,760 --> 03:42:10,200 WE KNOW TO HAVE HIGHER TOXICITY 4848 03:42:10,200 --> 03:42:11,920 PROFILE AND FOR SAKE OF TIME I 4849 03:42:11,920 --> 03:42:14,600 WILL SAY THIS IS THE CURRENT 4850 03:42:14,600 --> 03:42:16,920 ICANS MANAGEMENT STRATEGY AND 4851 03:42:16,920 --> 03:42:22,120 HIGHLIGHTING GRADE 3 WE 4852 03:42:22,120 --> 03:42:24,760 TYPICALLY DO LUMBAR PUNCTURE AND 4853 03:42:24,760 --> 03:42:26,960 DURING THAT TIME POINT IF NOT 4854 03:42:26,960 --> 03:42:31,280 CONCERNED FOR INFECTION WE 4855 03:42:31,280 --> 03:42:35,880 ADMINISTER -- GOAL PREVENTING 4856 03:42:35,880 --> 03:42:37,680 SEVERE LIFE THREATENING TOXICITY 4857 03:42:37,680 --> 03:42:41,840 IN PATIENTS RECEIVING CAR T-CELL 4858 03:42:41,840 --> 03:42:43,640 THERAPY THERE IS LARGE NEED TO 4859 03:42:43,640 --> 03:42:46,520 PATIENT POPULATION TO UTILIZE 4860 03:42:46,520 --> 03:42:48,320 BIOMARKERS AND PREDICTIVE 4861 03:42:48,320 --> 03:42:50,600 MODELING TO ASSESS PATIENTS WITH 4862 03:42:50,600 --> 03:42:52,280 SIGNIFICANT ICANS AS WE 4863 03:42:52,280 --> 03:42:54,760 DEVELOPED A RETROSPECTIVE STUDY 4864 03:42:54,760 --> 03:42:57,240 ALONGSIDE INSTITUTIONS PRESENT 4865 03:42:57,240 --> 03:43:00,560 HERE THAT ARE RETROSPECTIVE 4866 03:43:00,560 --> 03:43:02,400 NEUROIMAGING STUDY DATA BASE AND 4867 03:43:02,400 --> 03:43:04,840 BRAIN IMAGING FINDINGS AT 4868 03:43:04,840 --> 03:43:06,720 VARIOUS TIME POINTS CORRELATING 4869 03:43:06,720 --> 03:43:09,520 WITH ICANS AND I WOULD LIKE TO 4870 03:43:09,520 --> 03:43:10,840 INCORPORATE PRE-EMPTIVE 4871 03:43:10,840 --> 03:43:13,320 TREATMENT STRATEGIES TO PREVENT 4872 03:43:13,320 --> 03:43:15,480 WORSENING ICANS. WE ARE HERE TO 4873 03:43:15,480 --> 03:43:17,720 CONTINUE TO CONDUCT PRESCRIPTIVE 4874 03:43:17,720 --> 03:43:20,360 CLINICAL TRIALS COLLABORATIVELY 4875 03:43:20,360 --> 03:43:24,560 AND WE OPENED A THREE SITE 4876 03:43:24,560 --> 03:43:25,720 MULTICENTER TRIAL LOOKING AT 4877 03:43:25,720 --> 03:43:29,640 LONG TERM OUTCOMES AND -- POST 4878 03:43:29,640 --> 03:43:31,080 CAR T-CELL THERAPY AND WOULD 4879 03:43:31,080 --> 03:43:32,480 LOVE TO PROPOSE AND TALK TO 4880 03:43:32,480 --> 03:43:34,280 THOSE INTERESTED IN 4881 03:43:34,280 --> 03:43:35,920 NEUROTOXICITY WORKING MANAGEMENT 4882 03:43:35,920 --> 03:43:38,480 GROUP TO CONSIDER DEVELOPING A 4883 03:43:38,480 --> 03:43:40,600 MULTI-SITE INTERVENTIONAL STUDY 4884 03:43:40,600 --> 03:43:42,440 FOR THESE PATIENTS AND WITH THAT 4885 03:43:42,440 --> 03:43:50,520 I THANK YOU FOR YOUR ATTENTION. 4886 03:43:50,520 --> 03:43:55,000 >> NEXT IS KEVIN MCNERNEY FROM 4887 03:43:55,000 --> 03:44:01,840 JOHNS HOPKINS HOSPITAL. 4888 03:44:01,840 --> 03:44:07,040 >> THANKS SO MUCH. MY NAME IS 4889 03:44:07,040 --> 03:44:09,360 KEVIN MCNERNEY. 4890 03:44:09,360 --> 03:44:11,600 NO DISCLOSURES TO REPORT AND 4891 03:44:11,600 --> 03:44:13,200 JUST A BRIEF OUTLINE I WILL TALK 4892 03:44:13,200 --> 03:44:17,640 ABOUT CRS AND OVERLAP WITH HLH 4893 03:44:17,640 --> 03:44:22,360 AND GO INTO HLHLIKE TOXICITIES 4894 03:44:22,360 --> 03:44:25,440 INCLUDING DEFINITIONS THAT HAVE 4895 03:44:25,440 --> 03:44:27,440 BEEN USED SO FAR AND INCIDENCE 4896 03:44:27,440 --> 03:44:30,520 IN TIMING AND CLINICAL FINDINGS 4897 03:44:30,520 --> 03:44:33,720 AND CORE BIOLOGY AND OUTCOMES 4898 03:44:33,720 --> 03:44:35,760 AND POTENTIAL CONCLUSIONS AND 4899 03:44:35,760 --> 03:44:38,600 STARTING WITH OVERLAP OF 4900 03:44:38,600 --> 03:44:41,640 CYTOKINE SYNDROME AND HLH IS A 4901 03:44:41,640 --> 03:44:44,000 TERM INITIALLY USED TO DESCRIBE 4902 03:44:44,000 --> 03:44:47,840 A SYNDROME THAT OCCURRED WITH 4903 03:44:47,840 --> 03:44:50,080 CD3 MONOCLONAL ANTIBODY THAT 4904 03:44:50,080 --> 03:44:51,880 RESEMBLED WHAT WAS HAPPENING 4905 03:44:51,880 --> 03:44:56,040 WHEN MICE WERE DIRECTLY INJECTED 4906 03:44:56,040 --> 03:44:58,280 WITH CYTOKINES AND SYMPTOMS 4907 03:44:58,280 --> 03:45:00,280 RANGING WITH MILD FEVER MAIALGIA 4908 03:45:00,280 --> 03:45:03,160 AND NAUSHIA AND THIS HAS BEEN 4909 03:45:03,160 --> 03:45:07,200 OBSERVED BY SPECIFIC T-CELL 4910 03:45:07,200 --> 03:45:09,240 ENGAGERS AND STEM CELL 4911 03:45:09,240 --> 03:45:10,960 TRANSPLANT AND CAR T-CELL 4912 03:45:10,960 --> 03:45:14,600 THERAPY AND DISEASE BURDEN AND 4913 03:45:14,600 --> 03:45:20,840 ANCONTINUAL ENLOAD AND -- ARE 4914 03:45:20,840 --> 03:45:22,880 SIMILAR TO WHAT IS DESCRIBED IN 4915 03:45:22,880 --> 03:45:24,960 HLH AND BOTTOM RIGHT SEE WORKED 4916 03:45:24,960 --> 03:45:27,240 BY SHOWING PATIENTS WITH GRADE 4 4917 03:45:27,240 --> 03:45:32,280 TO 5CRS IN RED AND GRADE 0 TO 4918 03:45:32,280 --> 03:45:34,560 3CRS WITH OPEN CIRCLES THAT 4919 03:45:34,560 --> 03:45:38,680 THERE IS GREATER ELEVATION OF 4920 03:45:38,680 --> 03:45:41,160 INTERFERON GAMMA AND TO NAME A 4921 03:45:41,160 --> 03:45:42,920 FEW THAT ARE CONSISTENT WITH 4922 03:45:42,920 --> 03:45:45,560 WHAT IS SEEN IN HLH AND 4923 03:45:45,560 --> 03:45:49,000 SIMILARLY CRITERIA FOR HLH ARE 4924 03:45:49,000 --> 03:45:50,920 ALSO OFTEN MET BY HIGH GRADE C 4925 03:45:50,920 --> 03:45:54,560 ARE. S PATIENTS AND LEFT IS 4926 03:45:54,560 --> 03:45:57,640 HLH2004 CRITERIA DEVELOPED TO 4927 03:45:57,640 --> 03:46:00,720 DIAGNOSE HLH IN PRIMARY HLH 4928 03:46:00,720 --> 03:46:03,480 SETTING IN A CLINICAL TRIAL AND 4929 03:46:03,480 --> 03:46:06,720 ON RIGHT IS TABLE BY CAROLINE 4930 03:46:06,720 --> 03:46:09,120 WITH EACH ROW REPRESENTING A 4931 03:46:09,120 --> 03:46:13,440 PATIENT WITH GRADE 3 AND 4CRS 4932 03:46:13,440 --> 03:46:17,520 AND COLUMN WITH CRITERIA AND 4933 03:46:17,520 --> 03:46:22,080 MEETING SOME GRADE 3 PATIENTS AS 4934 03:46:22,080 --> 03:46:24,560 WELL RECOGNIZING THAT POST CAR T 4935 03:46:24,560 --> 03:46:26,840 BAR FOR HLH MIGHT BE HIGHER AND 4936 03:46:26,840 --> 03:46:31,000 SEEMS TO BE POPULATION THAT 4937 03:46:31,000 --> 03:46:32,720 EXPERIENCES EXTREME 4938 03:46:32,720 --> 03:46:34,000 HYPERINFLAMMATION AND TWO 4939 03:46:34,000 --> 03:46:38,240 DIFFERENT CRITERIA INITIALLY PUT 4940 03:46:38,240 --> 03:46:41,280 FORTH AND SUGGESTING THRESHOLD 4941 03:46:41,280 --> 03:46:48,160 OF OVER 10,000 CRS WITH ORGAN 4942 03:46:48,160 --> 03:46:54,440 TOXICITIES AND PHAGOCYTOSIS AND 4943 03:46:54,440 --> 03:46:57,120 -- 100,000 THAT WAS RECOMMENDED 4944 03:46:57,120 --> 03:47:00,480 IN A PATIENT WHO HAD CRS AND IN 4945 03:47:00,480 --> 03:47:03,600 ADDITION TO AT LEAST TWO ORGAN 4946 03:47:03,600 --> 03:47:07,440 TOXICITIES AND PHAGOCYTOSIS AND 4947 03:47:07,440 --> 03:47:10,920 CO AGROLOP OJY AND MOST DATA I 4948 03:47:10,920 --> 03:47:14,480 WILL PRESENT GOING FORWARD IS 4949 03:47:14,480 --> 03:47:17,240 USING THESE DEFINITIONS AND 4950 03:47:17,240 --> 03:47:18,680 WORKING GROUP DEVELOPED 4951 03:47:18,680 --> 03:47:20,560 CONSENSUS CRITERIA. I WILL SHOW 4952 03:47:20,560 --> 03:47:23,480 THEM AT THE END AND INCIDENCE 4953 03:47:23,480 --> 03:47:26,560 USING TWO DEFINITIONS RANGES AND 4954 03:47:26,560 --> 03:47:29,080 SEEMS IT DEPENDS ON CAR T-CELL 4955 03:47:29,080 --> 03:47:31,280 PRODUCT IT THAT IS BEING USED 4956 03:47:31,280 --> 03:47:33,200 AND INCIDENCE WAS REPORT TODAY 4957 03:47:33,200 --> 03:47:36,240 BE 35.6% THAT IS HIGHEST 4958 03:47:36,240 --> 03:47:37,160 REPORTED YET. 4959 03:47:37,160 --> 03:47:40,120 WITH CD19 CARS SEEMS LOWER 4960 03:47:40,120 --> 03:47:43,680 RANGING FROM 0 TO 14.8%. 4961 03:47:43,680 --> 03:47:46,000 MEDIAN ONSETS REPORTED A RANGE 4962 03:47:46,000 --> 03:47:49,640 FROM 9 TO 14 DAYS AND NOTABLY 4963 03:47:49,640 --> 03:47:51,920 YOU CAN SEE SOME PATIENTS 4964 03:47:51,920 --> 03:47:54,160 DEVELOP TOXICITY QUITE LATE WITH 4965 03:47:54,160 --> 03:47:57,960 LATEST HERE BEING 25 DAYS AFTER 4966 03:47:57,960 --> 03:48:00,200 CAR T-CELL INFUSION. 4967 03:48:00,200 --> 03:48:03,880 THEN THIS IS LOOKING AT CD22 4968 03:48:03,880 --> 03:48:06,160 DIRECTED EXPERIENCE THAT WE HAVE 4969 03:48:06,160 --> 03:48:09,080 MOST OF THE CORRELATIVE BIOLOGY 4970 03:48:09,080 --> 03:48:10,760 DATA IS FROM AND LAB FINDINGS 4971 03:48:10,760 --> 03:48:14,080 AND PATIENTS WITH CAR HLH ARE 4972 03:48:14,080 --> 03:48:17,360 SHOWN IN RED AND CRS IS SHOWN IN 4973 03:48:17,360 --> 03:48:22,280 BLUE AND THOSE TAKEAWAY ARE 4974 03:48:22,280 --> 03:48:24,080 HIGHER BILLY RUBIN LEVELS AND 4975 03:48:24,080 --> 03:48:25,920 COMPARED TO PATIENTS WHO JUST 4976 03:48:25,920 --> 03:48:30,000 HAD CRS AND MORE PROFOUND AND 4977 03:48:30,000 --> 03:48:33,600 PROLONGED NEUTROPENIA AND -- 4978 03:48:33,600 --> 03:48:37,600 WHEN CYTOKINES WERE EVALUATED 4979 03:48:37,600 --> 03:48:39,600 SIMILAR CYTOKINES TO WHAT HAS 4980 03:48:39,600 --> 03:48:44,320 BEEN DESCRIBED IN HLH IN THESE 4981 03:48:44,320 --> 03:48:46,240 PATIENTS THESE ARE PUT AT THE 4982 03:48:46,240 --> 03:48:48,040 TOP. THEY ARE MOST COMMONLY 4983 03:48:48,040 --> 03:48:49,720 TARGETED ONES AND THERE IS A 4984 03:48:49,720 --> 03:48:53,160 HOST OF OTHER MONOCITE AND 4985 03:48:53,160 --> 03:48:56,160 MACROFANL DERIVED CYTOKINES THAT 4986 03:48:56,160 --> 03:48:58,320 ARE HIGHER IN THIS GROUP AND 4987 03:48:58,320 --> 03:49:04,520 FROM ALPHA T-CELLS AND CELLULAR 4988 03:49:04,520 --> 03:49:07,360 KINETICS LOOKING AT T-CELL 4989 03:49:07,360 --> 03:49:08,840 PROLIFERATION IS HIGHER AND 4990 03:49:08,840 --> 03:49:11,800 PERSISTED AT DAY 28 AND ARE 4991 03:49:11,800 --> 03:49:15,120 FEWER PERIPHERAL BLOOD AND K 4992 03:49:15,120 --> 03:49:17,800 CELLS IN GROUP THAT HAD CAR HLH 4993 03:49:17,800 --> 03:49:20,360 THAT IS SHOWN BELOW WITH FEWER K 4994 03:49:20,360 --> 03:49:23,040 CELLS IN BASELINE AND GROUP OF 4995 03:49:23,040 --> 03:49:29,080 CAR HLH ON LEFT AND CAR T-CELL 4996 03:49:29,080 --> 03:49:32,200 EXPANSION THIS IS ACKREN TUATED 4997 03:49:32,200 --> 03:49:35,960 AND THEN AT D28 THESE CHANGES 4998 03:49:35,960 --> 03:49:38,120 WERE PERSISTENT AND ON FAR RIGHT 4999 03:49:38,120 --> 03:49:41,080 YOU SEE PATIENTS RECEIVING 5000 03:49:41,080 --> 03:49:46,800 T-CELL EXPANDED CAR T-CELLS AND 5001 03:49:46,800 --> 03:49:48,560 GREATER PROPORTION OF PATIENTS 5002 03:49:48,560 --> 03:49:50,800 THAT HAD T-CELL SELECTED 5003 03:49:50,800 --> 03:49:52,560 PRODUCTS DEVELOPED CAR 5004 03:49:52,560 --> 03:49:54,760 ASSOCIATED HLH. 5005 03:49:54,760 --> 03:49:58,520 SO, SHIFTING NOW TO CD19 5006 03:49:58,520 --> 03:50:00,080 DIRECTED CAR T-CELL PRODUCTS 5007 03:50:00,080 --> 03:50:02,920 THIS IS DATA FROM PEDIATRIC REAL 5008 03:50:02,920 --> 03:50:05,360 WORLD CONSORTIUM AND IDENTIFIED 5009 03:50:05,360 --> 03:50:07,720 A POPULATION DEVELOPING CARS HLH 5010 03:50:07,720 --> 03:50:11,280 AND LOOKED AT PREINFUSION LAB 5011 03:50:11,280 --> 03:50:14,840 VALUES FINDING BONE MARROW BLAST 5012 03:50:14,840 --> 03:50:17,480 REACTIVE PROTEIN FAIR ACONTINUE 5013 03:50:17,480 --> 03:50:19,920 AND PLATELETS WERE ASSOCIATED 5014 03:50:19,920 --> 03:50:22,560 WITH DEVELOPMENT OF CAR HRH AND 5015 03:50:22,560 --> 03:50:25,400 WE DEVELOPED THRESHOLDS USING 5016 03:50:25,400 --> 03:50:28,200 ROC ANALYSIS TO DETERMINE A 5017 03:50:28,200 --> 03:50:29,240 POINT TO HELP DISTINGUISH THOSE 5018 03:50:29,240 --> 03:50:31,200 THAT GO ON TO DEVELOP IT AND 5019 03:50:31,200 --> 03:50:33,280 THOSE THAT DON'T. WHEN ALL ARE 5020 03:50:33,280 --> 03:50:37,480 PUT INTO MULTIVARIABLE LOGISTIC 5021 03:50:37,480 --> 03:50:39,440 REGRESSION MODEL DISEASE BURDEN 5022 03:50:39,440 --> 03:50:42,640 AND LESS THAN 2% ARE PREDICTIVE 5023 03:50:42,640 --> 03:50:48,280 WHO GOES ON TO DEVELOP CAR HRH 5024 03:50:48,280 --> 03:50:50,320 AND MODEL BIOLOGY DESCRIBED 5025 03:50:50,320 --> 03:50:52,800 BEFORE B CELL BLASTS ACTIVATING 5026 03:50:52,800 --> 03:50:56,720 CAR T-CELL ACTIVATE AZ MACROFANL 5027 03:50:56,720 --> 03:51:00,160 AND CRS YOU HAVE NATURAL 5028 03:51:00,160 --> 03:51:01,640 REACTION TO CAR T-CELL AND 5029 03:51:01,640 --> 03:51:03,480 PROCESS WILL RESOLVE AND CAR 5030 03:51:03,480 --> 03:51:06,600 ASSOCIATED HLH WE PROPOSE 5031 03:51:06,600 --> 03:51:08,040 ACTIVATION OF T-CELLS AND 5032 03:51:08,040 --> 03:51:11,400 EXTREME ACTIVATION OF ENDOGENOUS 5033 03:51:11,400 --> 03:51:13,880 T-CELLS AND TISSUE INJURY OCCURS 5034 03:51:13,880 --> 03:51:17,280 AND EXCESSIVE ACTIVATION OF 5035 03:51:17,280 --> 03:51:19,720 CYTOKINE RELEASE AND POSITIVE 5036 03:51:19,720 --> 03:51:21,200 FEEDBACK LOOP AND DOWNREGULATION 5037 03:51:21,200 --> 03:51:24,680 OF T-CELLS WITH OTHER CELLS THAT 5038 03:51:24,680 --> 03:51:28,080 DOWNREGULATE T-CELLS THAT LEADS 5039 03:51:28,080 --> 03:51:32,440 TO HYPERFAIRO 10EMIA AND 5040 03:51:32,440 --> 03:51:35,480 SHIFTING TO OUTCOMES OF PATIENTS 5041 03:51:35,480 --> 03:51:40,280 DEVELOPING HLHLIKE TOXICITIES IS 5042 03:51:40,280 --> 03:51:43,600 DATA FROM PEDIATRIC WORLD AND WE 5043 03:51:43,600 --> 03:51:46,120 IDENTIFIED 26 PATIENTS 5044 03:51:46,120 --> 03:51:50,360 DEVELOPING HLH TOXICITIES OR 5045 03:51:50,360 --> 03:51:53,800 THESE AND FOUND THEY HAD 5046 03:51:53,800 --> 03:51:56,840 INFERIOR OVERALL SURVIVAL 5047 03:51:56,840 --> 03:51:58,080 COMPARED TO GROUP WITH GRADE 5048 03:51:58,080 --> 03:52:01,680 TWLEE OR 4CRS AND 12 MONTH 5049 03:52:01,680 --> 03:52:04,240 RELAPSE SURVIVAL ARE 25 AND 5% 5050 03:52:04,240 --> 03:52:06,240 AND SIMILAR OUTCOMES WERE SHOWN 5051 03:52:06,240 --> 03:52:10,480 IN PATIENTS DEVELOPING CAR HLH 5052 03:52:10,480 --> 03:52:14,880 AND ADULT LYMPHOMA PATIENTS 5053 03:52:14,880 --> 03:52:18,800 TREATED WITH AXI CELL AND 5054 03:52:18,800 --> 03:52:21,600 LOOKING AT CAUSES OF DAENL AND 5055 03:52:21,600 --> 03:52:25,880 PATIENTS DYING IN PEDIATRIC REAL 5056 03:52:25,880 --> 03:52:30,120 WORLD WHO DEVELOPED LEUKEMIA WAS 5057 03:52:30,120 --> 03:52:33,960 MAIN CAUSE AND OF THESE 5058 03:52:33,960 --> 03:52:37,120 INFECTIONS, DYING DRINKS CRS OR 5059 03:52:37,120 --> 03:52:40,240 ICANS AND CARDIAC FAILURE WHERE 5060 03:52:40,240 --> 03:52:41,880 CAUSE IS LISTED. 5061 03:52:41,880 --> 03:52:45,240 BECAUSE DATA HAS BEEN PRESENTED 5062 03:52:45,240 --> 03:52:47,560 UP TO NOW HAS BEEN USED 5063 03:52:47,560 --> 03:52:50,200 DIFFERING IN CRITERIA AND LARGE 5064 03:52:50,200 --> 03:52:52,320 EFFORT WAS MADE BY NIRALI TO 5065 03:52:52,320 --> 03:52:56,760 ORGANIZE THROUGH ASCT A GROUP OF 5066 03:52:56,760 --> 03:53:00,880 ONCOLOGIST, RUM TOLLS AND HLH 5067 03:53:00,880 --> 03:53:03,840 EXPERTS TO COME UP WITH 5068 03:53:03,840 --> 03:53:06,200 CONSENSUS CRITERIA AFTER IECS 5069 03:53:06,200 --> 03:53:08,600 AND THAT IS IECHS. 5070 03:53:08,600 --> 03:53:12,240 GOAL OF THIS IS TO UNIFY FIELD 5071 03:53:12,240 --> 03:53:15,560 GOING FORWARD TO BE ABLE TO 5072 03:53:15,560 --> 03:53:17,480 CHARACTERIZE IT BETTER IN TERMS 5073 03:53:17,480 --> 03:53:20,280 OF INCIDENCE AND OUTCOMES IN 5074 03:53:20,280 --> 03:53:23,040 CORRELATIVE BIOLOGY AND FOCUS TO 5075 03:53:23,040 --> 03:53:26,360 DISTINGUISH IS THAT MUCH OF THE 5076 03:53:26,360 --> 03:53:28,840 HLH LIKE TOXICITIES WE OBSERVE 5077 03:53:28,840 --> 03:53:31,400 MAY HAVE BEEN OVERLAPPING WITH 5078 03:53:31,400 --> 03:53:33,360 CRS AND GOAL TO DISTINGUISH 5079 03:53:33,360 --> 03:53:35,160 PATIENTS DEVELOPING LATER AFTER 5080 03:53:35,160 --> 03:53:38,840 RESOLUTION OF CRS AND GOING 5081 03:53:38,840 --> 03:53:41,440 FORWARD THAT IS ONE GOAL WE HAVE 5082 03:53:41,440 --> 03:53:44,440 TO CHARACTERIZE THAT BETTER AND 5083 03:53:44,440 --> 03:53:48,280 THROUGH THIS GROUP SUGGESTED 5084 03:53:48,280 --> 03:53:50,520 ICHS TREATMENT IS PUT FORTH 5085 03:53:50,520 --> 03:53:53,120 FOCUSED ON GROUP DEVELOPING 5086 03:53:53,120 --> 03:53:56,200 TOXICITIES AFTER RESOLUTION OF 5087 03:53:56,200 --> 03:53:58,120 CRS AND ONCE THESE HAVE BEEN 5088 03:53:58,120 --> 03:54:01,040 USED AND GIVEN INCREASE IN IO1 5089 03:54:01,040 --> 03:54:03,600 BETA AND IT WAS SUGGESTED AS 5090 03:54:03,600 --> 03:54:05,080 FIRST LINE THERAPY AND THOSE 5091 03:54:05,080 --> 03:54:07,160 WITH MORE SEVERE DISEASE OR 5092 03:54:07,160 --> 03:54:08,680 THOSE THAT DIDN'T RESPOND AND 5093 03:54:08,680 --> 03:54:12,160 STEROIDS HAVE NOW BEEN ADDED 5094 03:54:12,160 --> 03:54:13,400 CONSIDERING STARTING THOSE AND 5095 03:54:13,400 --> 03:54:14,240 CONSIDERING ADDING 5096 03:54:14,240 --> 03:54:16,600 [INDISCERNIBLE] AS WELL AND 5097 03:54:16,600 --> 03:54:20,720 THIRD LINER LIFE THREATENING 5098 03:54:20,720 --> 03:54:23,280 TOXICITIES GIVEN -- AND THESE 5099 03:54:23,280 --> 03:54:25,360 ARE BALANCED WITH CONCERN FOR 5100 03:54:25,360 --> 03:54:27,640 POTENTIAL IMPACT AND EFFICACY 5101 03:54:27,640 --> 03:54:32,520 FOR CAR T-CELLS AND TO CONCLUDE 5102 03:54:32,520 --> 03:54:37,000 HLHLIKE TOXICITIES THERE IS 5103 03:54:37,000 --> 03:54:43,000 TIMING IN PATIENTS DEVELOPING 5104 03:54:43,000 --> 03:54:44,600 TOXICITIES AND INCREASE 5105 03:54:44,600 --> 03:54:46,480 EXPANSION SUCH AS T-CELL 5106 03:54:46,480 --> 03:54:51,640 SELECTION AND DISEASE BURDEN AND 5107 03:54:51,640 --> 03:54:53,800 INCREASE T-CELL DOWN REGULATION 5108 03:54:53,800 --> 03:54:56,560 AND DESCRIBED SURVIVALS ARE POOR 5109 03:54:56,560 --> 03:55:00,400 AND CONSENSUS CRITERIA RECENTLY 5110 03:55:00,400 --> 03:55:01,920 DEVELOPED FOR BETTER 5111 03:55:01,920 --> 03:55:03,040 CHARACTERIZATIONS OF RISK 5112 03:55:03,040 --> 03:55:04,320 FACTORS AND TREATMENT OUTCOMES 5113 03:55:04,320 --> 03:55:08,160 AND NEXT STEPS ARE TO DO 5114 03:55:08,160 --> 03:55:09,480 RETROSPECTIVE DATA COLLECTION 5115 03:55:09,480 --> 03:55:11,240 STUDYING TOXICITY AND POTENTIAL 5116 03:55:11,240 --> 03:55:14,320 TRIALS FOR USING PREVENTIVE 5117 03:55:14,320 --> 03:55:16,800 THERAPIES AND PATIENTS WITH HIGH 5118 03:55:16,800 --> 03:55:20,440 RISK OF THIS TOXICITY. THANK 5119 03:55:20,440 --> 03:55:30,560 YOU S- 5120 03:55:46,160 --> 03:55:49,600 >> I'M A CLINICAL INVESTIGATOR 5121 03:55:49,600 --> 03:55:51,880 FOR STUDIES AT ST. JUDE AND 5122 03:55:51,880 --> 03:55:53,760 FORTUNATE TO WORK WITH MANY IN 5123 03:55:53,760 --> 03:55:55,880 AUDIENCE TODAY DEVELOPING A 5124 03:55:55,880 --> 03:56:03,040 PROSPECTIVE MULTICENTERED STUDY. 5125 03:56:03,040 --> 03:56:05,000 >> TO START TO SUMMARIZE CURRENT 5126 03:56:05,000 --> 03:56:07,080 STATE OF KNOWLEDGE ABOUT WHAT 5127 03:56:07,080 --> 03:56:09,720 DELAYED TOXICITIES LOOK LIKE WE 5128 03:56:09,720 --> 03:56:11,160 NEED MORE INFORMATION AND WE 5129 03:56:11,160 --> 03:56:13,200 HEARD THROUGHOUT DAY INITIAL 5130 03:56:13,200 --> 03:56:16,560 FOCUS IS DESCRIBING ACUTE 5131 03:56:16,560 --> 03:56:19,560 TOXICITY PROFILE ESTABLISHING 5132 03:56:19,560 --> 03:56:21,640 EFFICACY PREVENTING RELAPSE AND 5133 03:56:21,640 --> 03:56:27,240 START TO SEE PATTERNS EMERGING 5134 03:56:27,240 --> 03:56:37,800 WITH COHORT INTEGRATING THIS IN 5135 03:56:40,840 --> 03:56:43,760 STANDARD OF CARE. 5136 03:56:43,760 --> 03:56:47,000 PRIORITIES SUPPOSED TO HAPPEN IN 5137 03:56:47,000 --> 03:56:51,360 BUILDING IN SPRING OF 2020 5138 03:56:51,360 --> 03:56:54,360 IMPACT OF INFECTIONS AND ONGOING 5139 03:56:54,360 --> 03:56:56,600 DELAYED CONSTITUTION AS INITIAL 5140 03:56:56,600 --> 03:56:58,080 PRIORITIES AND THINKING FOR MORE 5141 03:56:58,080 --> 03:56:59,720 OF A TRADITIONAL LATE OF 5142 03:56:59,720 --> 03:57:02,240 EXCELLENCE WE KNOW IT IS 5143 03:57:02,240 --> 03:57:03,880 IMPORTANT TO CONSIDER AND 5144 03:57:03,880 --> 03:57:05,800 SUBSEQUENT MALIGNANCIES WHAT 5145 03:57:05,800 --> 03:57:08,480 HAPPENS TO REST OF ORGANS WE 5146 03:57:08,480 --> 03:57:09,640 HAVEN'T HIGHLIGHTED YET AND WHAT 5147 03:57:09,640 --> 03:57:12,440 IT MEANS FOR PATIENTS FROM 5148 03:57:12,440 --> 03:57:14,160 PSYCHOSOCIAL STANDPOINT AND 5149 03:57:14,160 --> 03:57:15,800 STARTING WITH BONE MARROW 5150 03:57:15,800 --> 03:57:17,560 DISFUNCTION AREA WE ARE STARTING 5151 03:57:17,560 --> 03:57:19,160 TO SEE CLINICAL QUESTIONS POP 5152 03:57:19,160 --> 03:57:19,600 UP. 5153 03:57:19,600 --> 03:57:23,560 SO, WE KNOW WHEN WE GIVE LYMPHO 5154 03:57:23,560 --> 03:57:27,680 DEPLETING CHEMOTHERAPY FOLLOWED 5155 03:57:27,680 --> 03:57:32,160 BY T-CELL -- LOOKING AT PACE OF 5156 03:57:32,160 --> 03:57:33,800 RECOVERY IT IS BIMODAL 5157 03:57:33,800 --> 03:57:35,040 DISTRIBUTION MAJORITY OF 5158 03:57:35,040 --> 03:57:37,320 PATIENTS RECOVER IN THE FIRST 5159 03:57:37,320 --> 03:57:40,040 MONTH AND SMALLER SUBSET 5160 03:57:40,040 --> 03:57:42,080 CONTINUE TO HAVE LOW COUNTS 5161 03:57:42,080 --> 03:57:44,240 PERSISTING OUT MONTHS AND MONTHS 5162 03:57:44,240 --> 03:57:48,520 AFTER THEY RECEIVED THEIR 5163 03:57:48,520 --> 03:57:50,280 THERAPY DEFINITIONS USING WORD 5164 03:57:50,280 --> 03:57:52,440 DELAYED AND SUBACUTE AND 5165 03:57:52,440 --> 03:57:54,160 POPULATION HASN'T GROWN TO HAVE 5166 03:57:54,160 --> 03:57:56,360 LARGE COHORT IN WHAT IS TRUE 5167 03:57:56,360 --> 03:57:58,760 EFFECTS OF SURVIVORSHIP AND 5168 03:57:58,760 --> 03:57:59,400 POPULATION AND IMPORTANT 5169 03:57:59,400 --> 03:58:00,960 TIMEFRAME TO CONSIDER AND 5170 03:58:00,960 --> 03:58:02,480 LOOKING BEYOND FIRST MONTH INTO 5171 03:58:02,480 --> 03:58:07,200 FIRST MONTH AND 2 YEARS AFTER 5172 03:58:07,200 --> 03:58:08,720 THERAPY CONSIDERING TALKING 5173 03:58:08,720 --> 03:58:13,600 ABOUT CRYTOPINAS IN CONSTRUCTS. 5174 03:58:13,600 --> 03:58:16,360 WHAT WE BEGIN TO OBSERVE GOES 5175 03:58:16,360 --> 03:58:20,080 BEYOND THAT WHILE NO CONSENSUS 5176 03:58:20,080 --> 03:58:21,720 DEFINITIONS YESTERDAY WE START 5177 03:58:21,720 --> 03:58:29,760 WITH DIAGNOSIS SEVERE PLASTIC 5178 03:58:29,760 --> 03:58:32,400 ENEMIA AND THERE IS CASES WITH 5179 03:58:32,400 --> 03:58:34,760 PEOPLE WITH CRYTOPINAS RELATED 5180 03:58:34,760 --> 03:58:38,360 TO PROCESSES AUTO IMMUNE OR 5181 03:58:38,360 --> 03:58:39,520 DISSTRUCKTIVE AND LOOKING TO SEE 5182 03:58:39,520 --> 03:58:42,000 RISK FACTORS LOOKING FOR 5183 03:58:42,000 --> 03:58:44,200 DEVELOPING THIS CONSIDER 5184 03:58:44,200 --> 03:58:45,440 BASELINE CRYTOPENIAS AND 5185 03:58:45,440 --> 03:58:47,320 PATIENTS EXPERIENCING TREATMENTS 5186 03:58:47,320 --> 03:58:50,480 FOR CYTOKINE RELEASE SYNDROME 5187 03:58:50,480 --> 03:58:53,800 AND MANY HYPOTHESIZE PRIOR BONE 5188 03:58:53,800 --> 03:58:55,600 MARROW TRANSPLANT MIGHT BE RISK 5189 03:58:55,600 --> 03:58:59,040 FACTOR DON'T HAVE DATA TO SUPOWE 5190 03:58:59,040 --> 03:59:03,640 RT THAT THERE IS PREDICTIVE 5191 03:59:03,640 --> 03:59:04,520 SCORES VALIDATED LOOKING AT 5192 03:59:04,520 --> 03:59:08,600 MEASURES OF BASELINE 5193 03:59:08,600 --> 03:59:10,400 INFLAMMATION NOT VALIDATED IN 5194 03:59:10,400 --> 03:59:11,440 PEDIATRIC SETTING AND 5195 03:59:11,440 --> 03:59:12,680 SUMMARIZING WHEN PEOPLE ARE 5196 03:59:12,680 --> 03:59:15,040 DOING WITH PATIENTS IN MOMENT 5197 03:59:15,040 --> 03:59:17,480 LOOKING TO ACQUIRE MORE DATA 5198 03:59:17,480 --> 03:59:18,880 BEYOND STANDARD TRANSFUSION 5199 03:59:18,880 --> 03:59:20,240 SUPPORT WE PROVIDE INITIAL 5200 03:59:20,240 --> 03:59:22,440 QUESTION THAT COMES UP IS WHAT 5201 03:59:22,440 --> 03:59:26,280 IS ROLE OF GROWTH FACTORS IN 5202 03:59:26,280 --> 03:59:28,520 POPULATION MANY ARE HESITANT 5203 03:59:28,520 --> 03:59:31,440 USING FACTORS WITH CONCERN IT 5204 03:59:31,440 --> 03:59:35,920 MAY PROMPT OR WORSEN SYMPTOMS OF 5205 03:59:35,920 --> 03:59:38,000 CYTOKINE SYNDROME USED SPARINGLY 5206 03:59:38,000 --> 03:59:40,440 IN POPULATIONS IN INIRNL 5207 03:59:40,440 --> 03:59:42,640 EXPERIENCE AND CASES COMING OUT 5208 03:59:42,640 --> 03:59:46,400 WITH SEVERE INFECTION IN 5209 03:59:46,400 --> 03:59:49,360 CRYTOPENIAS GCSF IS USED AND 5210 03:59:49,360 --> 03:59:52,720 EARLIER USE COMING OUT AGAIN IN 5211 03:59:52,720 --> 03:59:56,080 ADULT LYMPHOMA SETTING SESSION. 5212 03:59:56,080 --> 03:59:58,600 CAUTION AND WEIGHING RISKS AND 5213 03:59:58,600 --> 04:00:00,280 BENEFITS FOR ANY GIVEN PATIENT 5214 04:00:00,280 --> 04:00:02,840 AND EMERGING AREA IS FOR 5215 04:00:02,840 --> 04:00:05,040 PATIENTS WITH PRIOR BONE MARROW 5216 04:00:05,040 --> 04:00:07,840 TRANSPLANT WITH ONGOING SEVERE 5217 04:00:07,840 --> 04:00:11,080 CRYTOPENIAS USING CD4 SELECTED 5218 04:00:11,080 --> 04:00:13,160 STEM CELL BOOST TO RECOVER 5219 04:00:13,160 --> 04:00:15,200 ACCOUNTS AND PEDIATRIC CASE 5220 04:00:15,200 --> 04:00:17,480 REPORTS COMING OUT AND SHOWING 5221 04:00:17,480 --> 04:00:19,160 IN PATIENTS THIS IS EFFECTIVE 5222 04:00:19,160 --> 04:00:20,920 WAY TO RECOVER ACCOUNTS AND 5223 04:00:20,920 --> 04:00:23,280 SMALL COHORT CAN GO ON TO HAVE 5224 04:00:23,280 --> 04:00:26,240 SUSTAINED RESPONSES AND OF 5225 04:00:26,240 --> 04:00:31,760 COURSE LEUKO PINA REQUIREMENT 5226 04:00:31,760 --> 04:00:34,360 FOR IMMUNOGOB YOU'LLANCE 5227 04:00:34,360 --> 04:00:35,400 SUPPLEMENTATION AND RISK IS 5228 04:00:35,400 --> 04:00:38,080 ONGOING AND WILL TALK ABOUT IT 5229 04:00:38,080 --> 04:00:42,920 IN NEXT PORTION AND MOVING TO 5230 04:00:42,920 --> 04:00:46,040 NEUROTOXICITY AS HANEEN 5231 04:00:46,040 --> 04:00:49,000 DISCUSSED WE SEE THIS RECOVER 5232 04:00:49,000 --> 04:00:50,400 AFTER FIRST FEW WEEKS OF 5233 04:00:50,400 --> 04:00:52,240 TREATMENT. HAVEN'T LOOKED TO 5234 04:00:52,240 --> 04:00:53,800 SEE YET WHAT PATIENTS HAVE AS 5235 04:00:53,800 --> 04:00:56,400 FAR AS NEUROCOGNITIVE FUNCTION 5236 04:00:56,400 --> 04:00:59,520 AND IMAGING CHARACTERISTICS OR 5237 04:00:59,520 --> 04:01:00,960 MARKERS LATE EFFECTS 5238 04:01:00,960 --> 04:01:02,680 EXPERIENCING TOXICITIES AND 5239 04:01:02,680 --> 04:01:04,680 ADULT SETTING WHERE THEY START 5240 04:01:04,680 --> 04:01:06,320 TODAY INCORPORATE PATIENT 5241 04:01:06,320 --> 04:01:08,920 REPORTED NEUROOUTCOMES PATIENTS 5242 04:01:08,920 --> 04:01:11,360 REPORT HIGHER INCIDENCE OF MOOD 5243 04:01:11,360 --> 04:01:12,840 DISORDERS COMPARED TO HEALTHY 5244 04:01:12,840 --> 04:01:14,760 POPULATION AND LOOKING AT 5245 04:01:14,760 --> 04:01:17,480 PATIENT REPORTED OUTCOMES AS 5246 04:01:17,480 --> 04:01:19,360 COMPARE TER REPORTING CAR TO 5247 04:01:19,360 --> 04:01:22,000 OTHER THERAPIES SUCH AS 5248 04:01:22,000 --> 04:01:24,000 TRANSPLANTS AND ADULT SETTINGS 5249 04:01:24,000 --> 04:01:25,880 CAR HAS FAVORABLE PROFILE AND 5250 04:01:25,880 --> 04:01:28,680 GROUP LOOKING HOW TO INTEGRATE 5251 04:01:28,680 --> 04:01:31,560 INTO UP FRONT STUDIES AND HOW TO 5252 04:01:31,560 --> 04:01:33,440 INCORPORATE MOVING FORWARD AND 5253 04:01:33,440 --> 04:01:35,880 PEDIATRIC SURVIVORSHIP COHORT 5254 04:01:35,880 --> 04:01:38,640 AND BLA POPULATION WE HAVE TO 5255 04:01:38,640 --> 04:01:43,400 THINK IMPACT OF PRIOR THERAPIES 5256 04:01:43,400 --> 04:01:46,000 AND PRIOR TRANSPLANTS CAN IMPACT 5257 04:01:46,000 --> 04:01:47,120 NEUROOUTCOMES AND WE NEED TO 5258 04:01:47,120 --> 04:01:51,720 COLLECT THAT DATA ALONG WITH CAR 5259 04:01:51,720 --> 04:01:53,160 TREATMENT RELATED INFORMATION. 5260 04:01:53,160 --> 04:01:56,320 OTHER ORGANS IN ACUTE PHASE WE 5261 04:01:56,320 --> 04:01:58,320 HAVE SEEN IMPACT ON HEART AND 5262 04:01:58,320 --> 04:02:00,160 KIDNEYS AND PARTICULARLY IN 5263 04:02:00,160 --> 04:02:03,680 PATIENTS EXPERIENCING CYTOKINE 5264 04:02:03,680 --> 04:02:05,440 RELEASE SYNDROME AND IN GENERAL 5265 04:02:05,440 --> 04:02:07,400 THIS APPEARS IN SETTING WE HAVE 5266 04:02:07,400 --> 04:02:09,680 NOT LOOKED WHAT IT MEANS GOING 5267 04:02:09,680 --> 04:02:13,440 FORWARD HIGHER INCIDENCE OF LATE 5268 04:02:13,440 --> 04:02:15,200 CARDIAC EFFECTS OR TOXICITIES 5269 04:02:15,200 --> 04:02:17,000 AND ADULT SETTINGS WE HAVE SEEN 5270 04:02:17,000 --> 04:02:20,280 A HANDFUL OF LATE IMMUNE EVENTS 5271 04:02:20,280 --> 04:02:22,360 WITH MORE AUTO IMMUNE PHENOTYPE 5272 04:02:22,360 --> 04:02:24,360 THAT IS NOT REPORTED IN 5273 04:02:24,360 --> 04:02:27,520 PEDIATRICS AND SOMETHING TO LOOK 5274 04:02:27,520 --> 04:02:29,400 FOR AND PARTICULAR INTEREST FROM 5275 04:02:29,400 --> 04:02:31,400 PEDIATRIC STANDPOINT FROM 5276 04:02:31,400 --> 04:02:32,560 SURVIVORSHIP LENS WHAT IS IMPACT 5277 04:02:32,560 --> 04:02:36,720 FROM PATIENTS IN TERMS OF ENDO 5278 04:02:36,720 --> 04:02:38,840 KIND GROWTH FOR WHEN PATIENT IS 5279 04:02:38,840 --> 04:02:40,680 DECIDING ABOUT WEIGHING RIFBLG 5280 04:02:40,680 --> 04:02:43,480 AND BENEFIT OF GOING TO 5281 04:02:43,480 --> 04:02:46,520 TRANSPLANT VERSUS CAR T AS A 5282 04:02:46,520 --> 04:02:48,280 DEFINITIVE THERAPY AND OVERALL 5283 04:02:48,280 --> 04:02:49,640 FROM SAFETY STANDPOINT WE ARE 5284 04:02:49,640 --> 04:02:51,880 INTERESTED IN POTENTIAL IMPACT 5285 04:02:51,880 --> 04:02:55,880 ON RISK OF SUBSEQUENT MALIGNANT 5286 04:02:55,880 --> 04:02:57,480 NEOPLASMS AND FRAMING BASELINE 5287 04:02:57,480 --> 04:02:59,040 POPULATION RISK IN POPULATION 5288 04:02:59,040 --> 04:03:02,000 FOR PATIENTS WHO ARE SURVIVORS 5289 04:03:02,000 --> 04:03:06,600 OF RELAPSE REFRACTORY BL 5290 04:03:06,600 --> 04:03:07,960 UNDERGONE A TRANCE PLANT WE 5291 04:03:07,960 --> 04:03:10,000 THINK OF RISK OF 4% THIS IS 5292 04:03:10,000 --> 04:03:12,400 HEIGHTENED IN PATIENTS WITH 5293 04:03:12,400 --> 04:03:14,240 KNOWN CANCER PREDISPOSITION 5294 04:03:14,240 --> 04:03:15,680 SYNDROMES AND INITIAL WORK 5295 04:03:15,680 --> 04:03:17,280 COMING OUT OF COHORT FOUND A 5296 04:03:17,280 --> 04:03:20,280 RATE OF 1.5% AND IN LINE WITH 5297 04:03:20,280 --> 04:03:22,520 WHAT IS EXPECTED IN POPULATION 5298 04:03:22,520 --> 04:03:24,920 BECAUSE OF UNDERLYING RATE IS SO 5299 04:03:24,920 --> 04:03:26,920 LOW WE NEED BIG NUMBERS TO START 5300 04:03:26,920 --> 04:03:29,160 TO DRAW COMPARISONS BETWEEN 5301 04:03:29,160 --> 04:03:31,080 THERAPIES IT IS REASSURING WHEN 5302 04:03:31,080 --> 04:03:33,560 YOU LOOK AT ADULT COHORT WHERE'S 5303 04:03:33,560 --> 04:03:35,200 NUMBERS ARE BIGGER THEIR RATES 5304 04:03:35,200 --> 04:03:37,320 ARE PARALLELING ANL-RELATED 5305 04:03:37,320 --> 04:03:40,200 RISKS THAT ARE CLOSER TO 15% IN 5306 04:03:40,200 --> 04:03:43,320 THEIR POPULATION AND PHENOTYPE 5307 04:03:43,320 --> 04:03:45,760 SEEING FOR MALIGNANCIES EXPECTED 5308 04:03:45,760 --> 04:03:49,000 FOR AGE-RELATED RISKS AND I WILL 5309 04:03:49,000 --> 04:03:51,680 CLOSE WITH VISION AND HOW WE CAN 5310 04:03:51,680 --> 04:03:54,520 START TO WORK TOGETHER TO BEGIN 5311 04:03:54,520 --> 04:03:57,480 ANSWERING QUESTIONS IN SUBACUTE 5312 04:03:57,480 --> 04:03:59,320 AND DELAYED TOXICITY SPACE AND 5313 04:03:59,320 --> 04:04:01,320 DEVELOPING STUDY PLANNING TO 5314 04:04:01,320 --> 04:04:03,760 INITIATE IN PILOT PHASE ACROSS 9 5315 04:04:03,760 --> 04:04:06,160 PEDIATRIC CENTERS LOOKING AT CAR 5316 04:04:06,160 --> 04:04:08,360 T-CELL RECIPIENTS HIGHLIGHTING 5317 04:04:08,360 --> 04:04:11,120 INTERVAL FROM 3 MONTHS TO 2 5318 04:04:11,120 --> 04:04:13,280 YEARS AS THERAPY IN FIRST ROUND 5319 04:04:13,280 --> 04:04:14,800 AND PARTNERING WITH AS MAR CELLA 5320 04:04:14,800 --> 04:04:17,240 DESCRIBED THIS MORNING TO TRY TO 5321 04:04:17,240 --> 04:04:20,920 REDUCE BURDEN OF DATA ENTRY 5322 04:04:20,920 --> 04:04:22,320 REDUCING PREVENTION ACROSS 5323 04:04:22,320 --> 04:04:24,200 MULTIPLE DIFFERENT STUDIES AND 5324 04:04:24,200 --> 04:04:25,480 FORMATS AND OUR GOAL WITH THE 5325 04:04:25,480 --> 04:04:27,640 STUDY IS THAT WE CAN LOOK NOT 5326 04:04:27,640 --> 04:04:30,040 JUST WITHIN A POPULATION 5327 04:04:30,040 --> 04:04:31,680 RECEIVING 1 CAR T-CELL PRODUCT 5328 04:04:31,680 --> 04:04:33,280 OR ONE INDICATION AND REALLY 5329 04:04:33,280 --> 04:04:34,880 DESIGNING THIS IN WAY THAT WE 5330 04:04:34,880 --> 04:04:37,080 CAN BUILD UPON AS WE HOPE 5331 04:04:37,080 --> 04:04:39,200 THERAPIES FOR MALIGNANCIES AND 5332 04:04:39,200 --> 04:04:40,960 SOLID TUMORS WILL GROW WITH US 5333 04:04:40,960 --> 04:04:42,560 OVER THE NEXT COUPLE OF YEARS 5334 04:04:42,560 --> 04:04:46,760 AND SO WILL INTEGRATING STANDARD 5335 04:04:46,760 --> 04:04:49,280 METRICS FOR COMPREHENSIVE 5336 04:04:49,280 --> 04:04:51,240 EVALUATION IN PATIENTS LOOKING 5337 04:04:51,240 --> 04:04:54,680 AT CLINICAL DATA AND BUY LOGIC 5338 04:04:54,680 --> 04:04:56,520 CORRELATES AND FOCUS KNOWING 5339 04:04:56,520 --> 04:04:59,480 COHORT IS ENRICHED FOR BLA 5340 04:04:59,480 --> 04:05:01,560 PATIENTS IN AREAS THAT HAVE HAD 5341 04:05:01,560 --> 04:05:04,520 EMERGING SIGNALS FROM INITIAL 5342 04:05:04,520 --> 04:05:06,160 DATA INCORPORATING EXPLORATORY 5343 04:05:06,160 --> 04:05:08,760 AIMS WITH SYSTEMATIC EVALUATION 5344 04:05:08,760 --> 04:05:11,720 OF ORGAN SYSTEM TOXICITIES 5345 04:05:11,720 --> 04:05:13,280 REPORTING PATIENT OUTCOMES AS 5346 04:05:13,280 --> 04:05:16,520 WELL TO PICK UP SIGNALS EARLIER 5347 04:05:16,520 --> 04:05:17,600 ACROSS EXPANDED INDICATIONS AND 5348 04:05:17,600 --> 04:05:18,640 OUR GOAL IS REALLY THINKING 5349 04:05:18,640 --> 04:05:21,760 ABOUT DOING THIS IN A SYSTEMATIC 5350 04:05:21,760 --> 04:05:23,360 WAY SO WE CAN GET MOST 5351 04:05:23,360 --> 04:05:26,880 INFORMATION FROM OUR POPULATION. 5352 04:05:26,880 --> 04:05:31,240 THANK YOU. 5353 04:05:31,240 --> 04:05:33,680 >> ALL RIGHT. WE WILL LASTLY 5354 04:05:33,680 --> 04:05:36,520 HAVE JOSHUA HILL FROM FED HUTCH 5355 04:05:36,520 --> 04:05:39,320 SPEAK ABOUT VACCINATION AND 5356 04:05:39,320 --> 04:05:40,360 IMMUNOCONSTITUTION IN A 5357 04:05:40,360 --> 04:05:41,480 PRE-RECORDED SESSION. 5358 04:05:41,480 --> 04:05:48,040 >> ORGANIZING COMMITTEE FOR IN 5359 04:05:48,040 --> 04:05:52,160 -- RECIPIENTS AND HOPE TO REVIEW 5360 04:05:52,160 --> 04:05:54,320 WHAT WE LEARNED IN PAST FEW 5361 04:05:54,320 --> 04:05:56,520 YEARS AND GAPS WE NEED TO 5362 04:05:56,520 --> 04:05:57,800 UNDERSTAND MOVING FORWARD AND 5363 04:05:57,800 --> 04:05:59,920 APOLOGIZE I CAN'T BE THERE IN 5364 04:05:59,920 --> 04:06:01,480 PERSON AND LOOK FORWARD TO 5365 04:06:01,480 --> 04:06:06,480 DISCUSSING AT END OF THE SES 5366 04:06:06,480 --> 04:06:06,760 SESSION. 5367 04:06:06,760 --> 04:06:07,960 THESE ARE MY DISCLOSURES AND 5368 04:06:07,960 --> 04:06:11,040 WILL TALK ABOUT IMMUNE DEFICITS 5369 04:06:11,040 --> 04:06:12,360 CAR T-CELL THERAPY AND WHAT WE 5370 04:06:12,360 --> 04:06:14,680 KNOW IN THIS AREA. MOVING 5371 04:06:14,680 --> 04:06:17,360 QUICKLY TIME IS LIMITED HERE 5372 04:06:17,360 --> 04:06:20,000 DON'T NEED TO DWELL TOO MUCH ON 5373 04:06:20,000 --> 04:06:22,640 FACT THIS AUDIENCE CAR T-CELL 5374 04:06:22,640 --> 04:06:27,200 RECIPIENTS HAVE HIGH STATE OF 5375 04:06:27,200 --> 04:06:29,800 IMMUNO -- IN RELATION TO 5376 04:06:29,800 --> 04:06:32,840 UNDERLYING HEMATOLOGIC THERAPY 5377 04:06:32,840 --> 04:06:37,000 AND PATIENTS RECEIVED PRECAR 5378 04:06:37,000 --> 04:06:40,160 THERAPY ALL CONTRIBUTE TO IMMUNE 5379 04:06:40,160 --> 04:06:42,680 SUPPRESSION AND FACTORS 5380 04:06:42,680 --> 04:06:44,360 PRIMARILY B CELL DEPLETION WE 5381 04:06:44,360 --> 04:06:46,720 SEE AS RESULT OF CAR T-CELLS IN 5382 04:06:46,720 --> 04:06:48,840 PATIENT POPULATION IN ADDITION 5383 04:06:48,840 --> 04:06:52,680 TO TOXICITIES CRS AND ICANS 5384 04:06:52,680 --> 04:06:54,880 ASSOCIATED IMMUNOSUPPRESSION WE 5385 04:06:54,880 --> 04:06:57,120 HEARD ABOUT IN PRIOR TALKS AND 5386 04:06:57,120 --> 04:06:58,720 LEADING TO THESE AND WE ARE 5387 04:06:58,720 --> 04:07:00,680 LEARNING TO WHAT DEGREE THIS 5388 04:07:00,680 --> 04:07:03,720 IMPACTS PATHOGEN SPECIFIC 5389 04:07:03,720 --> 04:07:06,040 ANTI-BEAUEDIES OR PATHOGEN 5390 04:07:06,040 --> 04:07:09,080 SPECIFIC T-CELL IMMUNE MEMORY IN 5391 04:07:09,080 --> 04:07:11,880 PATIENTS RECOVERING IN CARS AND 5392 04:07:11,880 --> 04:07:15,800 STAT JIS IMPLEMENTED IN 5393 04:07:15,800 --> 04:07:17,360 IMMUNOGLOBIN THERAPY AND WE WILL 5394 04:07:17,360 --> 04:07:20,360 TALK ABOUT ANTI-MICROBIAL 5395 04:07:20,360 --> 04:07:22,000 PROPHYLAXIS AND VARIETY OF 5396 04:07:22,000 --> 04:07:25,160 PAPERS LOOKING AT CONSTITUTION 5397 04:07:25,160 --> 04:07:26,920 AFTER CAR T-CELL THERAPY THAT IS 5398 04:07:26,920 --> 04:07:30,680 A QUICK SNAPSHOT FROM PAPER BY 5399 04:07:30,680 --> 04:07:35,680 FRED'S GROUP IN MOV ET AND 5400 04:07:35,680 --> 04:07:40,440 LYMPHOCYTE ACCOUNTS AND CD19B 5401 04:07:40,440 --> 04:07:41,680 CELL ACCOUNTS ORIGINATE AROUND 5402 04:07:41,680 --> 04:07:44,840 DAY 30 AND SLOWLY RECOVER OVER 5403 04:07:44,840 --> 04:07:47,720 OF A YEAR AND ABSENT IN PATIENTS 5404 04:07:47,720 --> 04:07:49,640 THAT RESPOND IN 6 MONTHS AND SEE 5405 04:07:49,640 --> 04:07:51,920 A SUBSET OF PATIENTS BEGINNING 5406 04:07:51,920 --> 04:07:55,520 TO HAVE RECOVERY AND TOTAL IGG 5407 04:07:55,520 --> 04:07:57,880 DATA SHOWS A LITTLE OF A DROP 5408 04:07:57,880 --> 04:08:01,640 AFTER FIRST MONTH OR SO THAT IS 5409 04:08:01,640 --> 04:08:03,320 PERSISTENT WITH RECOVERY A YEAR 5410 04:08:03,320 --> 04:08:05,760 OR FURTHER OUT. BY ONE YEAR 10% 5411 04:08:05,760 --> 04:08:07,480 OF PATIENTS CONTINUE TO HAVE 5412 04:08:07,480 --> 04:08:11,200 SOME DEGREE OF CRYTOPENIA AFTER 5413 04:08:11,200 --> 04:08:14,240 CAR T INFUSION FOR VARIETY OF 5414 04:08:14,240 --> 04:08:15,320 FACTORS WE DON'T HAVE TIME TO 5415 04:08:15,320 --> 04:08:16,560 GET INTO TODAY. 5416 04:08:16,560 --> 04:08:19,240 THIS IS A COMPLICATED SLIDE I 5417 04:08:19,240 --> 04:08:20,720 WILL WALK THROUGH TO MAKE KEY 5418 04:08:20,720 --> 04:08:22,760 POINTS AND IS A CROSS-SECTIONAL 5419 04:08:22,760 --> 04:08:25,280 STUDY IN INDIVIDUALS RECEIVING 5420 04:08:25,280 --> 04:08:28,760 CD19 OR BCMA CAR SOME AREPEDIA 5421 04:08:28,760 --> 04:08:30,440 THE TRICK PATIENTS A YEAR OR UP 5422 04:08:30,440 --> 04:08:32,840 TO 5 YEARS OUT LOOKING AT 5423 04:08:32,840 --> 04:08:34,680 DIFFERENT IMMUNE METRICS IN 5424 04:08:34,680 --> 04:08:36,800 BLOOD AND DATA IS PATIENT TIME 5425 04:08:36,800 --> 04:08:39,160 POINT HERE AND TOTAL IGG WE 5426 04:08:39,160 --> 04:08:41,320 DIDN'T HAVE PEDIATRIC PATIENTS 5427 04:08:41,320 --> 04:08:45,800 ON PLOT ALL RECEIVING IVG AND 5428 04:08:45,800 --> 04:08:47,520 MEASUREMENTS WERE CONFOUNDED AND 5429 04:08:47,520 --> 04:08:49,280 SEE A MIX 12 MONTHS UP TO 5 5430 04:08:49,280 --> 04:08:51,840 YEARS OF PATIENTS BELOW NORMAL 5431 04:08:51,840 --> 04:08:53,760 IGG LEVEL AND THOSE THAT ARE 5432 04:08:53,760 --> 04:08:57,760 ABOVE WITH AND WITHOUT IV 5433 04:08:57,760 --> 04:09:00,760 REPLACEMENT LOOK AT TOTAL IGA IN 5434 04:09:00,760 --> 04:09:03,000 BLUE SQUARES ARE PEDIATRIC 5435 04:09:03,000 --> 04:09:05,080 PATIENTS SEEING 12 MONTHS TO 5 5436 04:09:05,080 --> 04:09:08,160 YEARS OUT AND NO PATIENTS TESTED 5437 04:09:08,160 --> 04:09:11,200 IN COHORT HAD MEASURABLE IGA AND 5438 04:09:11,200 --> 04:09:14,360 SAME STORY IN BLUE SQUARES 5439 04:09:14,360 --> 04:09:16,040 PEDIATRIC PATIENTS FOR IGM UP TO 5440 04:09:16,040 --> 04:09:18,640 5 YEARS PATIENTS WE TESTED HAD 5441 04:09:18,640 --> 04:09:23,640 NO IGM DETECTIBLE CIRCULATION 5442 04:09:23,640 --> 04:09:26,760 AND SIMILARLY CELL COUNT SPREAD 5443 04:09:26,760 --> 04:09:29,600 IN ADULT PATIENTS SOME WITH 5444 04:09:29,600 --> 04:09:31,680 RECOVERY AND SEEMS TO BE 5445 04:09:31,680 --> 04:09:35,160 DIFFERENT AND HAVE PROLONGED 5446 04:09:35,160 --> 04:09:36,920 IMMUNE DEFICIENCY 5447 04:09:36,920 --> 04:09:38,680 CROSS-SECTIONAL STUDY WE LOOKED 5448 04:09:38,680 --> 04:09:41,320 AT SAME TIME POINTS AND 5449 04:09:41,320 --> 04:09:43,040 INDIVIDUALS 12 MONTHS OUT TO SEE 5450 04:09:43,040 --> 04:09:45,640 HOW WELL THEY RETAINED PRIOR 5451 04:09:45,640 --> 04:09:48,880 PATHOGEN SPECIFIC ANTIBODIES TO 5452 04:09:48,880 --> 04:09:50,320 VACCINE PREVENTIBLE INFECTIONS 5453 04:09:50,320 --> 04:09:53,120 THAT ARE ON X AXIS AND Y AXIS IS 5454 04:09:53,120 --> 04:09:55,200 PROPORTION OF PATIENTS TESTED 5455 04:09:55,200 --> 04:09:58,520 WITH PROTECTIVE LEVEL IN BLUE OR 5456 04:09:58,520 --> 04:10:03,240 CD19 CAR T RECIPIENTS ADULTS ON 5457 04:10:03,240 --> 04:10:07,160 THIS PLOT AND PATIENTS ARE 5458 04:10:07,160 --> 04:10:09,320 PROTECTED AND OTHERS YOU SUSPECT 5459 04:10:09,320 --> 04:10:11,440 PROTECTION IS NOT AS GOOD AND 5460 04:10:11,440 --> 04:10:14,160 PATIENTS CAN RETAIN PROTECTIVE 5461 04:10:14,160 --> 04:10:17,280 ANTIBODIES WITH CD19BC DEPLETION 5462 04:10:17,280 --> 04:10:21,720 AND TARGETING PLASMA CELLS WITH 5463 04:10:21,720 --> 04:10:24,480 THIS YOU SEE FEWER PROPORTION OF 5464 04:10:24,480 --> 04:10:26,600 PATIENTS HERE ARE PROTECTED 5465 04:10:26,600 --> 04:10:29,800 GIVING INSIGHTS YOU EXPECT 5466 04:10:29,800 --> 04:10:31,240 KNOCKING OUT IMMUNE CELL SUBS 5467 04:10:31,240 --> 04:10:34,840 AND TARGETS HAVE IMMUNE 5468 04:10:34,840 --> 04:10:36,880 [INDISCERNIBLE] FOR IMMUNE 5469 04:10:36,880 --> 04:10:40,000 SYSTEM AND LONGITUDINAL STUDY 5470 04:10:40,000 --> 04:10:42,240 COLLECTING SAMPLES AND INCLUDING 5471 04:10:42,240 --> 04:10:46,840 PEDIATRICS AND ADULTS ARE DATA 5472 04:10:46,840 --> 04:10:49,680 BASELINE PRECAR T INFUSION WITH 5473 04:10:49,680 --> 04:10:58,120 TEENS 11 TO 18 AND ADULTS 18 AND 5474 04:10:58,120 --> 04:10:58,440 OLDER. 5475 04:10:58,440 --> 04:11:01,880 WHAT YOU CAN SEE FOR THE MOST 5476 04:11:01,880 --> 04:11:03,440 PART IS CHILDREN AND YOUNG 5477 04:11:03,440 --> 04:11:05,560 ADULTS ARE SIMILAR TO ADULTS AND 5478 04:11:05,560 --> 04:11:08,760 IF ANYTHING THEY HAVE HIGHER 5479 04:11:08,760 --> 04:11:12,320 BASELINE PROTECTIVE ANTIBODY 5480 04:11:12,320 --> 04:11:19,120 [INDISCERNIBLE] FOR DIFFERENT 5481 04:11:19,120 --> 04:11:19,960 VACCINE PREVENTABLE INFECTIONS 5482 04:11:19,960 --> 04:11:23,200 AND NOTABLY 60 TO 70% OF 5483 04:11:23,200 --> 04:11:24,480 PEDIATRIC PATIENTS HAD 5484 04:11:24,480 --> 04:11:26,760 [INDISCERNIBLE] TO HEPATITIS TO 5485 04:11:26,760 --> 04:11:29,400 MUMPS TO MEASLES AND RUBELLA AND 5486 04:11:29,400 --> 04:11:31,240 THERE IS A LARGE CHUNK OF 5487 04:11:31,240 --> 04:11:33,800 PATIENTS GOING INTO CAR T 5488 04:11:33,800 --> 04:11:35,360 THERAPY WITHOUT PROTECTIVE 5489 04:11:35,360 --> 04:11:37,720 TIGHTERS AND WITH PEDIATRIC 5490 04:11:37,720 --> 04:11:39,360 PATIENTS WITH PROTECTIVE 5491 04:11:39,360 --> 04:11:40,560 TIGHTERS WE STILL DON'T 5492 04:11:40,560 --> 04:11:42,320 UNDERSTAND TRANL ECTRY AFTER CAR 5493 04:11:42,320 --> 04:11:42,960 T THERAPY. 5494 04:11:42,960 --> 04:11:45,040 WHAT CAN WE DO ABOUT THIS? 5495 04:11:45,040 --> 04:11:48,080 VACCINATION IS OBVIOUSLY AN 5496 04:11:48,080 --> 04:11:50,720 IMPORTANT STRATEGY IN INFECTION 5497 04:11:50,720 --> 04:11:52,600 PREVENTION AND TRANSPLANT 5498 04:11:52,600 --> 04:11:54,520 PATIENTS AND WILL BE IN CAR T 5499 04:11:54,520 --> 04:11:56,560 PATIENTS AS WELL AND DON'T 5500 04:11:56,560 --> 04:11:58,280 UNDERSTAND WELL HOW PATIENTS 5501 04:11:58,280 --> 04:12:00,480 RESPOND AND WHEN TO GIVE 5502 04:12:00,480 --> 04:12:00,760 VACCINES. 5503 04:12:00,760 --> 04:12:02,280 WE HAVE DONE STUDIES AND OTHERS 5504 04:12:02,280 --> 04:12:04,280 HAVE AS WELL TRYING TO FOCUS ON 5505 04:12:04,280 --> 04:12:06,080 THIS QUESTION AND LOOKING AT 5506 04:12:06,080 --> 04:12:10,280 PRECAR VACCINES AND POST CAR 5507 04:12:10,280 --> 04:12:14,160 VACCINES AND USING SARS COV2 5508 04:12:14,160 --> 04:12:16,880 EXAMPLE STUDY WE DID PATIENTS 5509 04:12:16,880 --> 04:12:20,640 WITH TWO DOSES OF THE VACCINE 5510 04:12:20,640 --> 04:12:22,840 PRECAR DON'T MOUNT A GREAT 5511 04:12:22,840 --> 04:12:25,600 ANTIBODY TIGHTER WHAT THEY MOUNT 5512 04:12:25,600 --> 04:12:26,840 PERSISTS IN FIRST FEW MONTHS 5513 04:12:26,840 --> 04:12:29,080 THAT IS IMPORTANT AND YOU CAN 5514 04:12:29,080 --> 04:12:33,200 GET RESPONSE VACCINATING 3 TO 6 5515 04:12:33,200 --> 04:12:34,560 MONTHS AFTER CAR T-CELL THERAPY 5516 04:12:34,560 --> 04:12:36,720 AND WHAT YOU SEE IN PRECAR T 5517 04:12:36,720 --> 04:12:38,800 PERIOD IS PATIENTS HAVE GOOD 5518 04:12:38,800 --> 04:12:40,600 RESPONSE WITH T-CELL RESPONSE 5519 04:12:40,600 --> 04:12:46,840 THAT DROPS AS YOU EXPECT DAY 30 5520 04:12:46,840 --> 04:12:47,880 THAT BOUNCES BACK AND IS 5521 04:12:47,880 --> 04:12:50,160 IMPORTANT AND SUPPORTS CONCEPT 5522 04:12:50,160 --> 04:12:52,200 FOR CERTAIN PATHOGENS GIVING 5523 04:12:52,200 --> 04:12:54,760 PRECAR VACCINE COULD INDUCE 5524 04:12:54,760 --> 04:12:58,320 MEMORY THAT CAN SUBSEQUENTLY 5525 04:12:58,320 --> 04:13:00,800 RECOVER AND ESTABLISH IMMUNITY 5526 04:13:00,800 --> 04:13:01,880 PERSISTING AFTER A PERIOD OF 5527 04:13:01,880 --> 04:13:04,560 TIME FOR INITIAL CAR T INFUSION 5528 04:13:04,560 --> 04:13:07,520 AND WE DON'T HAVE TIME TO DIVE 5529 04:13:07,520 --> 04:13:09,480 INTO DETAILS OF PLOT BUT LOOKED 5530 04:13:09,480 --> 04:13:12,880 AT VARIETY OF CLINICAL MATRIX 5531 04:13:12,880 --> 04:13:14,920 AND DO A GOOD JOB PREDICTING 5532 04:13:14,920 --> 04:13:16,240 WHETHER A PATIENT WILL RESPOND 5533 04:13:16,240 --> 04:13:19,560 TO VACCINE AND SHOWED THAT IN 5534 04:13:19,560 --> 04:13:22,400 PATIENTS WITH UNDETECTABLE IGG 5535 04:13:22,400 --> 04:13:25,720 LEVELS AND UNDETECTABLE B CELLS 5536 04:13:25,720 --> 04:13:28,600 IN PROLIFERATION THEY COULD 5537 04:13:28,600 --> 04:13:30,240 MOUNT OF GOOD ANTIBODY RESPONSE 5538 04:13:30,240 --> 04:13:33,000 AND I THINK THIS GOES TO SHOW 5539 04:13:33,000 --> 04:13:35,040 THESE ARE NOT GREAT MATRIX FOR 5540 04:13:35,040 --> 04:13:38,440 WHAT IS HAPPENING IN LYMPH NODES 5541 04:13:38,440 --> 04:13:40,880 AND ASPECTS OF IMMUNE SYSTEM AND 5542 04:13:40,880 --> 04:13:42,240 DON'T HELP STRATIFY THAT WELL 5543 04:13:42,240 --> 04:13:43,800 WHO WILL RESPOND TO VACCINE OR 5544 04:13:43,800 --> 04:13:46,160 RIGHT TIME TO GIVE A VACCINE AND 5545 04:13:46,160 --> 04:13:48,120 ASIDE FROM COVID VACCINES AND 5546 04:13:48,120 --> 04:13:50,160 PAPER WE PUBLISHED ON FLU THERE 5547 04:13:50,160 --> 04:13:53,120 IS NOT MUCH OWE TLUT ON VACCINES 5548 04:13:53,120 --> 04:13:55,880 UNTIL THIS PAPER CAME OUT FOR 5549 04:13:55,880 --> 04:13:59,360 FRED LOCKE'S GROUP DOWN IN MOVE 5550 04:13:59,360 --> 04:14:05,520 ET LAST YEAR AFTER CAR T-CELL 5551 04:14:05,520 --> 04:14:07,520 THERAPY AFTER ADULTS SMALL STUDY 5552 04:14:07,520 --> 04:14:09,200 13 INDIVIDUALS WERE VACCINATED 5553 04:14:09,200 --> 04:14:11,840 AND WHEN YOU COMPARED BASELINE 5554 04:14:11,840 --> 04:14:15,240 TIGHTERS DAY 90 AND THEY GOT 5555 04:14:15,240 --> 04:14:17,640 VACCINATED LOOKING AT DAY 1-80 5556 04:14:17,640 --> 04:14:20,640 THERE IS NO IMPROVEMENT AND ARE 5557 04:14:20,640 --> 04:14:24,000 A HANDFUL OF PATIENTS 5558 04:14:24,000 --> 04:14:26,400 VACCINATION DAY 90 AND 180 AS 5559 04:14:26,400 --> 04:14:28,400 WELL AND SOME DIDN'T SEEM TO 5560 04:14:28,400 --> 04:14:31,320 BOOST TIGHTERS EITHER AND 5561 04:14:31,320 --> 04:14:32,960 PATIENTS NEED MULTIPLE ROUNDS OR 5562 04:14:32,960 --> 04:14:35,440 IT IS TOO EARLY BUT NOT 5563 04:14:35,440 --> 04:14:38,840 ENCOURAGING FROM EARLY VACCINE 5564 04:14:38,840 --> 04:14:39,440 RESPONSE. 5565 04:14:39,440 --> 04:14:43,280 ASIDE FROM SARS C- CO-V2 5566 04:14:43,280 --> 04:14:45,120 RESPONSE AND THREE MONTHS AFTER 5567 04:14:45,120 --> 04:14:47,840 CAR AND GETTING MORE DATA AND 5568 04:14:47,840 --> 04:14:50,360 ROUTINE VACCINES WE CONSIDER 5569 04:14:50,360 --> 04:14:53,840 POTENTIALLY GIVING VACCINES 6 5570 04:14:53,840 --> 04:14:58,520 MONTHS AFTER CAR T-CELL THERAPY 5571 04:14:58,520 --> 04:15:02,640 AND PATHOGENS AND VACCINATING 5572 04:15:02,640 --> 04:15:05,160 FOR THOSE WITH VACCINES 5573 04:15:05,160 --> 04:15:08,320 RECHECKING TIGHTERS AND 5574 04:15:08,320 --> 04:15:09,040 UNDERSTANDING PATIENTS SPONTDING 5575 04:15:09,040 --> 04:15:12,840 OR NOT AND BASED ON THAT WE 5576 04:15:12,840 --> 04:15:14,160 DETERMINED TO CONTINUE 5577 04:15:14,160 --> 04:15:16,160 MONITORING GIVING ADDITIONAL 5578 04:15:16,160 --> 04:15:18,560 VACCINES WAITING 6 MONTHS AND 5579 04:15:18,560 --> 04:15:20,120 RE-EVALUATE AND TRYING AGAIN AND 5580 04:15:20,120 --> 04:15:24,320 LEADING US TO TRY AGAIN PATIENTS 5581 04:15:24,320 --> 04:15:29,680 DEVELOP DETECTIBLE -- AND CD4 5582 04:15:29,680 --> 04:15:33,400 COUNT AS ABOVE 200 AND METRICS 5583 04:15:33,400 --> 04:15:35,280 DIDN'T DO GREAT JOB PREDICTING 5584 04:15:35,280 --> 04:15:37,320 AND SUPPORTING IMMUNE RECOVERY 5585 04:15:37,320 --> 04:15:39,760 AND INCREASED LIKELIHOOD OF THE 5586 04:15:39,760 --> 04:15:42,640 VACCINE RESPONSE. 5587 04:15:42,640 --> 04:15:53,000 HOW DO WE MANAGE THIS? THIS IS 5588 04:15:53,000 --> 04:15:53,880 IMPORTANT BRANCH POINT. 5589 04:15:53,880 --> 04:15:55,960 WE DON'T KNOW IF THERE ARE 5590 04:15:55,960 --> 04:15:58,280 PATIENTS THAT DON'T NEED IT AND 5591 04:15:58,280 --> 04:15:59,520 HOW FREQUENTLY SHOULD WE GIVE IT 5592 04:15:59,520 --> 04:16:01,920 AND HOW LONG TO TARGET SPECIFIC 5593 04:16:01,920 --> 04:16:07,080 IGG TIGHTERS IS ONGOING AREA OF 5594 04:16:07,080 --> 04:16:07,400 DISCUSSION. 5595 04:16:07,400 --> 04:16:11,000 THIS IS AN EXPENSIVE PRODUCT AS 5596 04:16:11,000 --> 04:16:13,280 SUB-QIGG REPLACEMENT COULD BE 5597 04:16:13,280 --> 04:16:15,400 BURDEN SOME AS WELL WE HAVE LOTS 5598 04:16:15,400 --> 04:16:18,680 TO LEARN IN PEDIATRIC PATIENTS 5599 04:16:18,680 --> 04:16:21,360 ABOUT COST BENEFITS HERE AND 5600 04:16:21,360 --> 04:16:24,440 WHAT IVIG MIGHT BE DOING FOR 5601 04:16:24,440 --> 04:16:25,920 PATIENTS IN THE LONG TERM AND I 5602 04:16:25,920 --> 04:16:27,200 MOVED QUICKLY THROUGH THAT. 5603 04:16:27,200 --> 04:16:29,320 THAT IS WHERE WE ARE WITH 5604 04:16:29,320 --> 04:16:32,320 CURRENT STATE OF UNDERSTANDING 5605 04:16:32,320 --> 04:16:35,720 IMMUNE RECOVERY AND VACCINATION 5606 04:16:35,720 --> 04:16:38,800 AND IMMUNOGLOB YOU'LLIN 5607 04:16:38,800 --> 04:16:40,160 REPLACEMENT STRATEGIES AND 5608 04:16:40,160 --> 04:16:41,920 BETTER TO UNDERSTAND PATIENTS 5609 04:16:41,920 --> 04:16:44,480 AND THANKING COLLABORATORS 5610 04:16:44,480 --> 04:16:45,760 ACROSS UNIVERSITY OF WASHINGTON 5611 04:16:45,760 --> 04:16:47,800 SYSTEM AND SEATTLE AND FUNDERS 5612 04:16:47,800 --> 04:16:50,200 OF WORK AND LOOK FORWARD TO 5613 04:16:50,200 --> 04:16:51,160 CHATTING WITH YOU DISCUSS 5614 04:16:51,160 --> 04:16:56,880 SECTION AND THANK YOU FOR YOUR 5615 04:16:56,880 --> 04:16:57,480 ATTENT 5616 04:16:57,480 --> 04:16:57,800 ATTENTION. 5617 04:16:57,800 --> 04:17:00,360 >> I THINK WE HAVE TIME FOR A 5618 04:17:00,360 --> 04:17:04,880 COUPLE QUESTIONS IF ANYONE HAS 5619 04:17:04,880 --> 04:17:09,440 A 5620 04:17:09,440 --> 04:17:09,640 ANY. 5621 04:17:09,640 --> 04:17:11,720 >> THANK YOU, EVERYBODY, FOR A 5622 04:17:11,720 --> 04:17:12,080 GREAT SESSION. 5623 04:17:12,080 --> 04:17:13,960 YOU KNOW, I WAS THINKING WE SEEM 5624 04:17:13,960 --> 04:17:15,720 LIKE WE ARE LEARNING MORE AND 5625 04:17:15,720 --> 04:17:17,480 MORE THAT WE DON'T NECESSARILY 5626 04:17:17,480 --> 04:17:19,280 NEED INFLAMMATION AFTER CAR. AT 5627 04:17:19,280 --> 04:17:22,280 LEAST IN ALL. I PONDER THIS 5628 04:17:22,280 --> 04:17:26,680 ALSO A LOT AS WE DO BRAIN TUMOR 5629 04:17:26,680 --> 04:17:29,200 TRIALS AS WELL. WE GET INTO 5630 04:17:29,200 --> 04:17:30,680 TROUBLES STILL THAT WE ARE 5631 04:17:30,680 --> 04:17:34,080 WORRIED WE WILL TURN OFF THE 5632 04:17:34,080 --> 04:17:34,400 CAR. 5633 04:17:34,400 --> 04:17:37,120 I'M CURIOUS WHAT PEOPLE'S 5634 04:17:37,120 --> 04:17:38,240 THOUGHTS ARE OF BLUNTING 5635 04:17:38,240 --> 04:17:42,160 INFORMATION WITH THINGS LIKE 5636 04:17:42,160 --> 04:17:44,160 STEROIDS EARLY TOESEE WE HAVE 5637 04:17:44,160 --> 04:17:46,520 SEEN SOME ARE TARGETED FOR SOME 5638 04:17:46,520 --> 04:17:48,080 THINGS BUT NOT ALWAYS GOOD FOR 5639 04:17:48,080 --> 04:17:51,720 ALL AND CURIOUS ABOUT PEOPLE'S 5640 04:17:51,720 --> 04:17:59,560 THOUGHTS ABOUT THAT QUESTION. 5641 04:17:59,560 --> 04:18:04,200 >> I THINK, YOU KNOW, 5642 04:18:04,200 --> 04:18:07,360 [INDISCERNIBLE] THERE IS A FEW 5643 04:18:07,360 --> 04:18:10,120 TIMES WITH PATIENTS WITH 98% 5644 04:18:10,120 --> 04:18:11,640 DISEASE IN BONE MARROW AND WE 5645 04:18:11,640 --> 04:18:13,840 REALLY DON'T WANT TO GO THERE 5646 04:18:13,840 --> 04:18:16,960 AND WE GIVE THEM CELLS AND DAY 2 5647 04:18:16,960 --> 04:18:20,160 AND 3 AND 4 WE WILL DO STEROIDS 5648 04:18:20,160 --> 04:18:21,840 AND THEY DO FINE AND I THINK IT 5649 04:18:21,840 --> 04:18:24,080 WOULD BE REALLY HELPFUL FOR US 5650 04:18:24,080 --> 04:18:26,320 TO UNDERSTAND A LITTLE BIT MORE 5651 04:18:26,320 --> 04:18:29,760 HOW T-CELLS ARE RESISTANT TO 5652 04:18:29,760 --> 04:18:30,840 STEROIDS AND THINK YOUR FIRST 5653 04:18:30,840 --> 04:18:33,640 POINT THAT WE ARE LEARNING YOU 5654 04:18:33,640 --> 04:18:35,800 DON'T NEED FOR INFLAMMATION FOR 5655 04:18:35,800 --> 04:18:38,480 CAR RESPONSES AND POTENTIALLY IF 5656 04:18:38,480 --> 04:18:42,680 WE DECREASE INFLAMMATION MAY 5657 04:18:42,680 --> 04:18:45,320 IMPROVE RESPONSES. 5658 04:18:45,320 --> 04:18:48,640 IT IS FOR THIS IN THE LAST YEAR 5659 04:18:48,640 --> 04:18:51,200 AND AS WE LEARN MORE WE CAN GET 5660 04:18:51,200 --> 04:18:54,320 TO THAT IDEAL STATE OF LETTING 5661 04:18:54,320 --> 04:18:55,560 T-CELLS HAVE FUNCTIONAL RESPONSE 5662 04:18:55,560 --> 04:18:59,960 ABOUT ALL OF THE EXCESS 5663 04:18:59,960 --> 04:19:05,080 INFLAMMATORY RESPONSE. 5664 04:19:05,080 --> 04:19:07,640 >> MINE IS NOT DIRECTED AT ONE 5665 04:19:07,640 --> 04:19:09,200 SPEAKER. YOU DID GREAT. AWARE 5666 04:19:09,200 --> 04:19:12,880 OF BIOMARKERS THAT COULD 5667 04:19:12,880 --> 04:19:14,320 POTENTIALLY CORRELATE WITH 5668 04:19:14,320 --> 04:19:15,800 TOXICITY WHERE THERE IS NO 5669 04:19:15,800 --> 04:19:17,760 CLINICAL PHENOTYPE FOR EXAMPLE 5670 04:19:17,760 --> 04:19:19,760 CYTOKINE THAT IS ELEVATED BUT 5671 04:19:19,760 --> 04:19:21,240 PATIENT DOESN'T COME IN WITH 5672 04:19:21,240 --> 04:19:24,560 FEVER OR CSF BIOMARKER BUT NEVER 5673 04:19:24,560 --> 04:19:26,600 DEVELOP ICANS? WOULD BE A NICE 5674 04:19:26,600 --> 04:19:28,760 GOAL TO HAVE A SURROGATE TEST 5675 04:19:28,760 --> 04:19:31,200 THAT TRACKS THINGS ARE GOING IN 5676 04:19:31,200 --> 04:19:34,880 THE RIGHT DIRECTION BUT THEN THE 5677 04:19:34,880 --> 04:19:45,280 PATIENT IS NOT SICK. 5678 04:19:51,560 --> 04:19:57,120 >> I HAVE A COMMENT ON CARRIE'S 5679 04:19:57,120 --> 04:19:59,480 VERY GOOD INITIAL POINT. I 5680 04:19:59,480 --> 04:20:02,880 THINK THAT I WOULD SAY THAT I AM 5681 04:20:02,880 --> 04:20:04,880 NOT SURE THAT WE KNOW FOR SURE. 5682 04:20:04,880 --> 04:20:07,120 I DON'T KNOW. IN MY MIND THE 5683 04:20:07,120 --> 04:20:08,800 JURY IS STILL OUT WHETHER YOU 5684 04:20:08,800 --> 04:20:10,440 NEED SOME INFLAMMATION AND YOU 5685 04:20:10,440 --> 04:20:12,520 MIGHT NOT NEED IT FOR INITIAL 5686 04:20:12,520 --> 04:20:16,280 RESPONSE BUT NOT SO SURE FOR 5687 04:20:16,280 --> 04:20:20,080 DURABLE RESPONSE. I KNOW I 5688 04:20:20,080 --> 04:20:21,880 THINK WE CAN'T NECESSARILY 5689 04:20:21,880 --> 04:20:23,360 EXTRAPOLATE AND SOME DATA I 5690 04:20:23,360 --> 04:20:27,520 AGREE WITH YOU I CAN'T FOLLOW 5691 04:20:27,520 --> 04:20:28,760 COHORTS ON THE KITE TRIAL AND 5692 04:20:28,760 --> 04:20:32,520 SOME DATA FROM THERE ARE EARLY 5693 04:20:32,520 --> 04:20:34,280 DECKS THAT LOOKED LIKE YOU MIGHT 5694 04:20:34,280 --> 04:20:36,440 HAVE IMPACT ON DURABLE 5695 04:20:36,440 --> 04:20:41,920 REMISSIONS AND I JUST WONDER 5696 04:20:41,920 --> 04:20:44,400 WHETHER YOU NEED A LOOK AND FOR 5697 04:20:44,400 --> 04:20:49,640 PATIENTS GOING TO 10 TORS CD19 5698 04:20:49,640 --> 04:20:52,320 NEGATIVE AND IS THERE TOXIN THAT 5699 04:20:52,320 --> 04:20:55,160 INFLAMMATION IS HELPING CLEAR 5700 04:20:55,160 --> 04:20:57,120 THAT IN THOSE PATIENTS? 5701 04:20:57,120 --> 04:20:59,560 WE NEED TO STUDY IT I THINK TO 5702 04:20:59,560 --> 04:21:00,440 FIGURE THAT OUT. 5703 04:21:00,440 --> 04:21:04,000 MY QUESTION IS AND THIS IS SORT 5704 04:21:04,000 --> 04:21:07,840 OF ALSO A COMMENT TO COMMENTARY 5705 04:21:07,840 --> 04:21:10,440 AND YOU BROUGHT UP, RICK, SOEBY 5706 04:21:10,440 --> 04:21:13,960 IS NOT SO INTERESTED IN STUDYING 5707 04:21:13,960 --> 04:21:16,200 [INDISCERNIBLE] BECAUSE IT IS 5708 04:21:16,200 --> 04:21:17,640 LOGISTICALLY CHALLENGING AND 5709 04:21:17,640 --> 04:21:22,400 COSTLY AND COSTLY COMPARED TO 5710 04:21:22,400 --> 04:21:24,080 GAMAFANT. I THINK THERE IS -- 5711 04:21:24,080 --> 04:21:26,160 WE DO NEED TO JUST KEEP IN MIND 5712 04:21:26,160 --> 04:21:28,520 THAT IT IS, YOU KNOW, VERY 5713 04:21:28,520 --> 04:21:30,680 INTERESTING AND IMPORTANT TO 5714 04:21:30,680 --> 04:21:35,720 STUDY GAMAFAN. WE HAVE TO KEEP 5715 04:21:35,720 --> 04:21:37,560 IN MINDS A LITTLE BIT OF COMPANY 5716 04:21:37,560 --> 04:21:39,960 MOTIVATION OF TRYING TO GET AN 5717 04:21:39,960 --> 04:21:42,400 EXPENSIVE PRODUCT TO USE MORE 5718 04:21:42,400 --> 04:21:44,720 THAN AN ANOTHER POPULATION. 5719 04:21:44,720 --> 04:21:51,040 SO, THAT IS A COMMENT ON THAT. 5720 04:21:51,040 --> 04:21:52,680 I WONDER WHAT YOUR THOUGHTS ARE 5721 04:21:52,680 --> 04:21:55,040 ON DO YOU THINK IT WILL BE 5722 04:21:55,040 --> 04:21:57,160 EASIER TO STUDY SOMETHING LIKE 5723 04:21:57,160 --> 04:21:59,880 THAT VERSUS ANAKIN RA? DO YOU 5724 04:21:59,880 --> 04:22:01,720 AGREE IT IS LOGISTICALLY HARD 5725 04:22:01,720 --> 04:22:03,280 WITH ANAKIN RA? 5726 04:22:03,280 --> 04:22:08,600 >> WE DON'T KNOW YET. 5727 04:22:08,600 --> 04:22:12,360 IN PART WE ARE A LITTLE 5728 04:22:12,360 --> 04:22:14,280 BEHOLDENED TO SOEBY AND WISH WE 5729 04:22:14,280 --> 04:22:20,840 COULD BE MORE ENTHUSIASTIC ABOUT 5730 04:22:20,840 --> 04:22:22,600 ANAKIN RA. [INDISCERNIBLE]. 5731 04:22:22,600 --> 04:22:23,960 >> 1 DOSE. 5732 04:22:23,960 --> 04:22:24,520 >> DOSING. 5733 04:22:24,520 --> 04:22:26,320 >> AND I DO THINK THAT IT WILL 5734 04:22:26,320 --> 04:22:28,400 BE REALLY INTERESTING AND THERE 5735 04:22:28,400 --> 04:22:30,680 IS MORE AND MORE DATA I THINK 5736 04:22:30,680 --> 04:22:36,520 COMING OUT FOR VARIOUS GROUPS 5737 04:22:36,520 --> 04:22:39,840 AND DATA A FEW WEEKS AGO 5738 04:22:39,840 --> 04:22:41,560 KEYSTONE AT TANDEM AND 5739 04:22:41,560 --> 04:22:42,960 COLLABORATING EARLY RESULTS WE 5740 04:22:42,960 --> 04:22:46,920 SEE THAT ARE POTENTIALLY 5741 04:22:46,920 --> 04:22:50,000 INHIBITING INTERFERON GAMA MIGHT 5742 04:22:50,000 --> 04:22:50,920 ENHANCE YOUR EFFICACIOUS 5743 04:22:50,920 --> 04:22:52,440 RESPONSE AND THINK YOUR POINT 5744 04:22:52,440 --> 04:22:54,680 ABOUT, YOU KNOW, BEING 5745 04:22:54,680 --> 04:22:56,440 INFLAMMATIONS POTENTIALLY TO 5746 04:22:56,440 --> 04:22:58,440 SOME DEGREE FOR DURABLE RESPONSE 5747 04:22:58,440 --> 04:23:01,040 REMAINS TO BE SEEN AND FOR SURE 5748 04:23:01,040 --> 04:23:03,920 YOU NEED EXPANSION OF T-CELLS 5749 04:23:03,920 --> 04:23:06,520 AND YOU WILL HAVE SOME AND IS 5750 04:23:06,520 --> 04:23:11,000 RECRUITMENT OF MONOCITES AND 5751 04:23:11,000 --> 04:23:16,040 MACROPHAGES TO DO THAT. 5752 04:23:16,040 --> 04:23:18,320 >> YEAH. THAT WOULD BE IDEAL IF 5753 04:23:18,320 --> 04:23:20,600 WE COULD AND WE DIDN'T NEED 5754 04:23:20,600 --> 04:23:20,800 THIS. 5755 04:23:20,800 --> 04:23:21,320 >> YEAH. 5756 04:23:21,320 --> 04:23:23,880 >> HOW MUCH -- OH, GOD. I DON'T 5757 04:23:23,880 --> 04:23:28,040 KNOW. I THINK $50,000. 5758 04:23:28,040 --> 04:23:29,400 >> LIQUID GOLD. 5759 04:23:29,400 --> 04:23:32,240 >> 50,000? I DON'T KNOW. 5760 04:23:32,240 --> 04:23:33,720 >> NOT AS MUCH AS 5761 04:23:33,720 --> 04:23:34,680 [INDISCERNIBLE]. 5762 04:23:34,680 --> 04:23:37,480 >> IN TERMS OF EXPERIENCE WITH 5763 04:23:37,480 --> 04:23:40,720 ANAKIN RA IT HAS BECOME BEST 5764 04:23:40,720 --> 04:23:43,320 FRIEND IN GD2 CAR I WILL HEAR 5765 04:23:43,320 --> 04:23:45,280 MORE FROM ROBBY LATER NOT 5766 04:23:45,280 --> 04:23:46,600 CHALLENGING TO USE AND WE CAN 5767 04:23:46,600 --> 04:23:49,560 GIVE -- YOU CAN GIVE A DRIP OR 5768 04:23:49,560 --> 04:23:51,040 INTERMITTENT DOSING ABOUT YOU WE 5769 04:23:51,040 --> 04:23:55,640 USE IT IN A STANDARD WAY. IT IS 5770 04:23:55,640 --> 04:23:57,320 ABOUT COST YOU KNOW AND 5771 04:23:57,320 --> 04:23:59,240 COMPANY'S INCENTIVE THAT IS A 5772 04:23:59,240 --> 04:24:00,800 SHAME THAT WE CAN'T MAKE 5773 04:24:00,800 --> 04:24:06,040 DECISIONS BASED ON OTHER 5774 04:24:06,040 --> 04:24:06,320 VARIABLES. 5775 04:24:06,320 --> 04:24:08,520 >> ONE LAST QUESTION? 5776 04:24:08,520 --> 04:24:10,800 >> GREAT TALKS BY EVERYBODY. 5777 04:24:10,800 --> 04:24:13,960 THIS QUESTION IS FOR HANEEN AND 5778 04:24:13,960 --> 04:24:16,320 GETTING TO ERA WITH BETTER 5779 04:24:16,320 --> 04:24:19,560 DEFINED GUIDELINES FOR GRADING 5780 04:24:19,560 --> 04:24:21,600 ICANS I START TO SEE IDEAS ABOUT 5781 04:24:21,600 --> 04:24:23,920 AS WE TRY TO MOVE TOWARDS 5782 04:24:23,920 --> 04:24:26,680 TREATING PATIENTS IN OUTPATIENT 5783 04:24:26,680 --> 04:24:29,640 SETTING POSSIBLY MONITORING 5784 04:24:29,640 --> 04:24:32,200 ICANS AND OTHER TOXICITY 5785 04:24:32,200 --> 04:24:33,400 REMOTELY THROUGH PATIENT 5786 04:24:33,400 --> 04:24:36,520 RESPONSES THROUGH APP OR PLUS OR 5787 04:24:36,520 --> 04:24:38,560 MINUS AI INCORPORATION AND IF 5788 04:24:38,560 --> 04:24:43,000 YOU HAVE THOUGHTS ON WHEN THIS 5789 04:24:43,000 --> 04:24:44,800 MIGHT BE FEASIBLE AND IF THIS IS 5790 04:24:44,800 --> 04:24:47,000 SOMETHING WE COULD POTENTIALLY 5791 04:24:47,000 --> 04:24:52,440 DO FOR PEDIATRICS OR IF THAT IS 5792 04:24:52,440 --> 04:24:55,120 STILL FAR AWAY. 5793 04:24:55,120 --> 04:24:57,920 >> I THINK THAT IS REALLY NEAT 5794 04:24:57,920 --> 04:25:00,280 AND THINK THAT IS SORT OF IN THE 5795 04:25:00,280 --> 04:25:04,160 NEXT STRATOSPHERE OF CAR LOOKING 5796 04:25:04,160 --> 04:25:06,600 IN TERMS OF NEUROTOXICITY THAT 5797 04:25:06,600 --> 04:25:08,560 IS A DIFFICULT THING TO ASSESS 5798 04:25:08,560 --> 04:25:12,440 FOR SUBTLE SIGNS AND ONCE IT IS 5799 04:25:12,440 --> 04:25:14,200 ACTUALLY STARTED YOU ARE LIKE 5800 04:25:14,200 --> 04:25:15,680 OKAY. WHAT DID WE MISS? 5801 04:25:15,680 --> 04:25:17,200 THAT IS WHAT I FEARED WOULD 5802 04:25:17,200 --> 04:25:19,760 HAPPEN IN TERMS OF AI TYPE OF 5803 04:25:19,760 --> 04:25:23,680 STRATEGY AND YOU RELY HEAVILY ON 5804 04:25:23,680 --> 04:25:27,320 PROBABLY NOT PATIENTS BUT MORESO 5805 04:25:27,320 --> 04:25:31,440 THE CAREGIVER. YOU LOSE NURSING 5806 04:25:31,440 --> 04:25:33,040 ASSESSMENT AND PHYSICIAN 5807 04:25:33,040 --> 04:25:35,080 ASSESSMENT AND KEEP PATIENTS 5808 04:25:35,080 --> 04:25:36,880 ADMITTED AND I'M BIASED WITH 5809 04:25:36,880 --> 04:25:39,960 THAT REGARDS REGARDS TO INFUSING 5810 04:25:39,960 --> 04:25:44,400 AND MONITORING AND WATCHING. 5811 04:25:44,400 --> 04:25:45,600 THAT WOULD BE PROBABLY EXCELLENT 5812 04:25:45,600 --> 04:25:50,080 TO GET TO A POINT TO DEVELOP AN 5813 04:25:50,080 --> 04:25:50,560 APP. 5814 04:25:50,560 --> 04:25:53,720 MAYBE I DON'T HAVE ENOUGH 5815 04:25:53,720 --> 04:25:55,640 FORESIGHT TO SEE THAT BUT MAYBE 5816 04:25:55,640 --> 04:25:59,480 NOT QUITE YET BUT WOULD BE COOL 5817 04:25:59,480 --> 04:26:01,880 TO SEE. 5818 04:26:01,880 --> 04:26:02,240 >> THANK YOU. 5819 04:26:02,240 --> 04:26:04,680 >> WELCOME TO 5820 04:26:04,680 --> 04:26:09,560 SECTION 4A. IF LOOKING FOR 4B, 5821 04:26:09,560 --> 04:26:11,040 PLEASE CROSS THE CORRIDOR. THIS 5822 04:26:11,040 --> 04:26:15,360 SECTION WE ARE LOOKING AT UNIQUE 5823 04:26:15,360 --> 04:26:19,120 POPULATIONS THAT A LOT OF US ARE 5824 04:26:19,120 --> 04:26:21,320 TRYING TO GET CAR T INTO. WE 5825 04:26:21,320 --> 04:26:25,320 WOULD LOVE TO DO THIS IN AN 5826 04:26:25,320 --> 04:26:26,880 ORGANIZED FASHION IN CLINICAL 5827 04:26:26,880 --> 04:26:28,800 TRIALS AND LOOK AT SOCIAL AND 5828 04:26:28,800 --> 04:26:31,480 ECONOMIC ISSUES SURROUNDING 5829 04:26:31,480 --> 04:26:33,880 ACCESS TO CAR T AND 5830 04:26:33,880 --> 04:26:35,120 PATIENT-REPORTED OUTCOMES AND 5831 04:26:35,120 --> 04:26:38,320 WOULD LIKE TO START WITH SARAH 5832 04:26:38,320 --> 04:26:39,640 FROM GREATER OREMAN STREET THAT 5833 04:26:39,640 --> 04:26:43,680 WILL TALK TO US ABOUT INFANTS 5834 04:26:43,680 --> 04:26:46,200 AND PATIENTS WITH DOWNSYNDROME. 5835 04:26:46,200 --> 04:26:47,920 >> THANK YOU VERY MUCH FOR 5836 04:26:47,920 --> 04:26:49,600 INVITING ME AND CURATING THIS 5837 04:26:49,600 --> 04:26:53,920 VERY EXCITING PART OF THE 5838 04:26:53,920 --> 04:26:57,920 SYMPOSIUM. DEALING WITH DOWN 5839 04:26:57,920 --> 04:26:59,880 SIN INFANTS AND USING 5840 04:26:59,880 --> 04:27:03,160 INFORMATION TO CONSIDER BROADER 5841 04:27:03,160 --> 04:27:09,480 GROUPS AS WELL. 5842 04:27:09,480 --> 04:27:17,760 IS THAT ON? THE MOUSE. GOT IT. 5843 04:27:17,760 --> 04:27:19,880 OKAY. CONSIDERING GENERALLY 5844 04:27:19,880 --> 04:27:23,600 THOUGHT MATRIX TERMS TO CONSIDER 5845 04:27:23,600 --> 04:27:25,600 YOU MIGHT WANT TO CONSIDER 5846 04:27:25,600 --> 04:27:28,640 FEASIBILITY IN RELATION TO PACE 5847 04:27:28,640 --> 04:27:33,520 OF DISEASE AND COMORBIDITIES 5848 04:27:33,520 --> 04:27:38,800 IMPACT ON ESSENTIAL INTRINSIC 5849 04:27:38,800 --> 04:27:41,280 DEFECTS AND UNDERSTAND DATA 5850 04:27:41,280 --> 04:27:42,880 EFFICACY OF SUBGROUP AND 5851 04:27:42,880 --> 04:27:44,240 CONSIDERING IMPACT OF 5852 04:27:44,240 --> 04:27:47,080 TOLLRABILITY OF EXPECTED 5853 04:27:47,080 --> 04:27:49,440 TOXICITIES AND WHETHER AN IMPACT 5854 04:27:49,440 --> 04:27:54,280 TO CONSOLIDATE ON STEM CELL 5855 04:27:54,280 --> 04:27:57,600 TRANSPLANTATION AROUND FOR 5856 04:27:57,600 --> 04:28:00,160 EXAMPLE COMORBIDITIES AND 5857 04:28:00,160 --> 04:28:04,160 APPLYING TO THINKING OF DOWNSIN 5858 04:28:04,160 --> 04:28:08,240 DROCHL AND ALL20-FOLD INCREASE 5859 04:28:08,240 --> 04:28:09,840 WE KNOW AND DEMONSTRATED 5860 04:28:09,840 --> 04:28:12,280 OUTCOMES IN GROUPS CONTRIBUTED 5861 04:28:12,280 --> 04:28:15,360 TO RELEVANT TOXICITIES IN TERMS 5862 04:28:15,360 --> 04:28:19,920 OF SEVERE INFECTIONS IMPACTING 5863 04:28:19,920 --> 04:28:22,120 THROUGHOUT THERAPY AND IN 5864 04:28:22,120 --> 04:28:25,560 SLIGHTLY DIFFERENT GENETIC 5865 04:28:25,560 --> 04:28:31,360 BACKGROUNDS ACTIVATING IN 5866 04:28:31,360 --> 04:28:35,640 PARTICULAR COHORT -- CERTAINLY 5867 04:28:35,640 --> 04:28:38,680 THERE ARE RELEVANT COMORBIDITIES 5868 04:28:38,680 --> 04:28:41,040 IN CARDIAC LESIONS AND EVIDENCE 5869 04:28:41,040 --> 04:28:43,880 THAT T-CELL COMPARTMENT IS NOT 5870 04:28:43,880 --> 04:28:46,040 SAME FOR NONDOWNSYNDROME 5871 04:28:46,040 --> 04:28:48,080 PATIENTS IN SMALLER NAÏVE POOL 5872 04:28:48,080 --> 04:28:50,080 THAT MIGHT IMPACT ON PRODUCT YOU 5873 04:28:50,080 --> 04:28:52,480 TAKE AND THAT YOU GENERATE AND 5874 04:28:52,480 --> 04:28:54,880 THERE IS QUITE SIGNIFICANT 5875 04:28:54,880 --> 04:28:56,200 EVIDENCE OF IMMUNE DISREGULATION 5876 04:28:56,200 --> 04:28:58,320 IN INNATE SYSTEM AS WELL AND ARE 5877 04:28:58,320 --> 04:29:01,200 SMALL STUDIES NOT WELL 5878 04:29:01,200 --> 04:29:02,760 CHARACTERIZING AND NOT 5879 04:29:02,760 --> 04:29:05,320 SYSTEMATICALLY CHARACTERIZED IN 5880 04:29:05,320 --> 04:29:07,080 DOWN SYNDROME PATIENT GROUPS AND 5881 04:29:07,080 --> 04:29:09,120 INTEREST IN TERMS WHAT IT MIGHT 5882 04:29:09,120 --> 04:29:11,840 MEAN IN TERMS OF PATIENT COHORTS 5883 04:29:11,840 --> 04:29:15,840 AND EFFICACY THERE IS TREATMENTS 5884 04:29:15,840 --> 04:29:17,920 AND STUDIES AND TALKING ABOUT 5885 04:29:17,920 --> 04:29:19,960 DATA NOW PUBLISHED AND IN TERMS 5886 04:29:19,960 --> 04:29:22,160 OF CONSIDERING DOWN SYNDROME 5887 04:29:22,160 --> 04:29:23,720 PATIENTS IN RELATION TO 5888 04:29:23,720 --> 04:29:25,600 TOLLRABILITY FOR EXAMPLE ABILITY 5889 04:29:25,600 --> 04:29:28,600 TO TOLERATE CYTOKINE SYNDROME 5890 04:29:28,600 --> 04:29:32,320 AND RELEASE THAT THEY MIGHT FACE 5891 04:29:32,320 --> 04:29:34,720 THAT IS OF IMPORTANCE AND INNATE 5892 04:29:34,720 --> 04:29:36,560 CHANGES NOTED MIGHT HAVE IMPACT 5893 04:29:36,560 --> 04:29:43,960 ON SEVERITY OF CRS ICANS COHORT 5894 04:29:43,960 --> 04:29:47,120 WITH RIFBLG FOR INFECTIONS THAT 5895 04:29:47,120 --> 04:29:50,240 IS OF CONCERN NEEDING TO BE 5896 04:29:50,240 --> 04:29:52,120 CONSIDERED AND PATIENTS 5897 04:29:52,120 --> 04:29:53,320 CONSIDERATING TRANSPLANT TAKING 5898 04:29:53,320 --> 04:29:56,360 INTO ACCOUNT IN TERMS OF ABILITY 5899 04:29:56,360 --> 04:29:57,600 WITHSTANDING CONDITIONING OR 5900 04:29:57,600 --> 04:30:00,600 MIGHT INDEED HAVE A TRANSPLANT 5901 04:30:00,600 --> 04:30:03,720 BEFOREHAND AND I GUESS THIS 5902 04:30:03,720 --> 04:30:05,920 WOULD BE THERAPY PERHAPS FOR 5903 04:30:05,920 --> 04:30:07,560 HIGH-RISK PATIENTS. WE DON'T 5904 04:30:07,560 --> 04:30:09,880 HAVE TO GUESS TOO MUCH. THIS 5905 04:30:09,880 --> 04:30:13,160 PRESENTED NICE DATA YOU THAT IS 5906 04:30:13,160 --> 04:30:14,800 RETROSPECTIVE DATA FROM THREE 5907 04:30:14,800 --> 04:30:18,040 STUDY PROTOCOLS THAT IS 5908 04:30:18,040 --> 04:30:19,840 INCORPORATING 17 PATIENTS AND 5909 04:30:19,840 --> 04:30:22,680 DOWN SYNDROME AND PATIENT NOT 5910 04:30:22,680 --> 04:30:28,240 INFUSED LEAVING 16 TO BE INFUSED 5911 04:30:28,240 --> 04:30:29,840 AND PRIOR STEM CELL TRANSPLANT 5912 04:30:29,840 --> 04:30:32,160 AND MEDIAN LINES CRYOTHERAPY 5913 04:30:32,160 --> 04:30:33,920 WERE TWO AND PERHAPS A BIT LESS 5914 04:30:33,920 --> 04:30:35,880 THAN WE SEE IN STANDARD COHORT 5915 04:30:35,880 --> 04:30:40,040 AND IN TERMS OF CR8S AND THESE 5916 04:30:40,040 --> 04:30:41,920 IN FIRST TWO BULLET POINTS YOU 5917 04:30:41,920 --> 04:30:43,840 SEE RATES ARE FAVORABLE COMPARED 5918 04:30:43,840 --> 04:30:47,520 TO DATA FROM NONDOWNSYNDROME 5919 04:30:47,520 --> 04:30:49,080 PATIENTS TREATED IN ELLI ANA 5920 04:30:49,080 --> 04:30:54,240 STUDY AND 13 MONTHS OVERALL 5921 04:30:54,240 --> 04:30:58,360 SURVIVAL NOT REACHED -- THE 5922 04:30:58,360 --> 04:31:00,040 PROBABILITY OF DURATION OF 5923 04:31:00,040 --> 04:31:02,880 RESPONSE WAS LOWER THAN IL-IANA 5924 04:31:02,880 --> 04:31:06,520 STUDY AND INTERVALS AND DON'T 5925 04:31:06,520 --> 04:31:08,760 MISS SIGNIFICANCE AND THREE ARE 5926 04:31:08,760 --> 04:31:13,440 DEFINED TO BE CD9 NEGATIVE AND 3 5927 04:31:13,440 --> 04:31:15,480 UNDEFIND AND COMPARING TO GROUP 5928 04:31:15,480 --> 04:31:20,560 OF ALL RESPONDERS AND KINETICS 5929 04:31:20,560 --> 04:31:24,160 WERE COMPARABLE. HERE ARE DATA 5930 04:31:24,160 --> 04:31:26,320 ON RELAPSE FREE SURVIVAL AND 5931 04:31:26,320 --> 04:31:27,600 OVERALL SURVIVAL AND 5932 04:31:27,600 --> 04:31:29,280 CHARACTERISTICS ARE SIMILAR TO 5933 04:31:29,280 --> 04:31:30,560 WHAT WE WOULD EXPECT FROM 5934 04:31:30,560 --> 04:31:32,480 PATIENTS TREATED WITH LICENSED 5935 04:31:32,480 --> 04:31:35,920 PRODUCT AND IN CONTEXT OF 5936 04:31:35,920 --> 04:31:37,680 NONDOWNSYNDROME PATIENTS ELAPSE 5937 04:31:37,680 --> 04:31:40,160 SURVIVAL IS LOWER AND SPEAKING 5938 04:31:40,160 --> 04:31:42,840 TO SLIGHTLY SHORTER DURATION OF 5939 04:31:42,840 --> 04:31:45,320 RESPONSE IN COHORT AND ARE SMALL 5940 04:31:45,320 --> 04:31:46,160 NUMBERS THAT [INDISCERNIBLE] 5941 04:31:46,160 --> 04:31:48,960 CAN'T BE DRAWN AND IN TERMS OF 5942 04:31:48,960 --> 04:31:51,720 TOXICITIES RATE OF GRADE 3 OR 4 5943 04:31:51,720 --> 04:31:55,960 AND EPAN GRADE 3 OR 4 SYNDROMES 5944 04:31:55,960 --> 04:31:58,200 EQUIVALENT IN NONDOWNSYNDROME 5945 04:31:58,200 --> 04:32:01,920 PATIENTS TREATED AND SEVERE 5946 04:32:01,920 --> 04:32:06,320 ICANS AND THIS IS EQUIVALENT TO 5947 04:32:06,320 --> 04:32:08,400 NONDOWNSYNDROME PATIENTS AND 5948 04:32:08,400 --> 04:32:12,520 RATE OF SEVERE INFECTIONS AND 5949 04:32:12,520 --> 04:32:14,040 SUGGESTING TOLLRABILITY OF 5950 04:32:14,040 --> 04:32:16,240 CRYTOPENIAS CAN'T BE MANAGED 5951 04:32:16,240 --> 04:32:18,400 THERE ARE FOUR DEATHS IN STUDY 5952 04:32:18,400 --> 04:32:19,960 AND THREE DYING OF DISEASE AND 5953 04:32:19,960 --> 04:32:26,000 ONE PATIENT IN CONTEXT OF CRS 5954 04:32:26,000 --> 04:32:27,000 CRANIOPATHY AND [INDISCERNIBLE] 5955 04:32:27,000 --> 04:32:29,120 AND LIKELY CELL IN CHILDREN AND 5956 04:32:29,120 --> 04:32:32,000 YOUNG ADULTS WITH DOWNSYNDROME 5957 04:32:32,000 --> 04:32:33,240 TO DELIVER RESPONSE RATE TO 5958 04:32:33,240 --> 04:32:36,040 LOWER OUTCOMES THAT OVERLAY 5959 04:32:36,040 --> 04:32:40,200 THOSE WITH NONDOWNSYNDROME 5960 04:32:40,200 --> 04:32:42,160 PATIENTS TREATING PROMINENT RATE 5961 04:32:42,160 --> 04:32:45,120 OF SEVERE INFECTIONS AND LATE 5962 04:32:45,120 --> 04:32:46,560 INFECTIONS IS NOT EXCESSIVE IN 5963 04:32:46,560 --> 04:32:48,480 THE COHORT THAT IS NOT 5964 04:32:48,480 --> 04:32:51,000 ENCOURAGING AND REFLECTS 5965 04:32:51,000 --> 04:32:52,600 INTERNALIZED EXPERIENCE WE HAVE 5966 04:32:52,600 --> 04:32:54,160 TREATED SUCCESSFULLY WITH 5967 04:32:54,160 --> 04:32:56,400 THERAPEUTIC IN CONTEXT OF 5968 04:32:56,400 --> 04:32:58,880 DOWNSYNDROME ALL AND GOING TO 5969 04:32:58,880 --> 04:33:00,440 CONSIDERATIONS OF THERAPY IN 5970 04:33:00,440 --> 04:33:02,920 YOUNGER CHILD AND PARTICULARLY 5971 04:33:02,920 --> 04:33:07,640 INFANTS WITH MLL REARRANGED 5972 04:33:07,640 --> 04:33:09,280 LEUKEMIAS APPLYING THOUGHT RATES 5973 04:33:09,280 --> 04:33:11,400 AGAIN AND SEEING PROGRESSIVE AND 5974 04:33:11,400 --> 04:33:13,080 HIGHLY AGGRESSIVE DISEASE AND 5975 04:33:13,080 --> 04:33:14,960 SORRY SOME THINGS ARE MOVING AND 5976 04:33:14,960 --> 04:33:17,120 THEY ARE BEING MODIFIED AND 5977 04:33:17,120 --> 04:33:19,480 FEASIBILITY OF A3 NEEDS TO BE 5978 04:33:19,480 --> 04:33:20,440 CONSIDERED AND SMALL CHILDREN 5979 04:33:20,440 --> 04:33:23,320 LESS THAN 10 KILOGRAMS AND THEY 5980 04:33:23,320 --> 04:33:24,680 DON'T HAVE RELEVANT EXPERIENCE 5981 04:33:24,680 --> 04:33:26,760 IN THAT AND IN OUR HANDS IS NOT 5982 04:33:26,760 --> 04:33:28,360 A PARTICULAR PROBLEM AND CONCERN 5983 04:33:28,360 --> 04:33:30,760 THAT INFANCY WOULD COLLECT 5984 04:33:30,760 --> 04:33:32,600 T-CELL POPULATION PREDOMINANTLY 5985 04:33:32,600 --> 04:33:34,600 NAÏVE AND ACTIVATED WOULDN'T BE 5986 04:33:34,600 --> 04:33:37,400 ABLE TO MAKE PRODUCT AND THAT 5987 04:33:37,400 --> 04:33:40,120 HASN'T BEEN BROUGHT OUT INTO 5988 04:33:40,120 --> 04:33:42,000 PRACTICAL EXPERIENCE AND 5989 04:33:42,000 --> 04:33:45,320 CHILDREN LESS THAN THREE YEARS 5990 04:33:45,320 --> 04:33:50,200 OF AGE CONTEXT OF SEVERE PRIOR 5991 04:33:50,200 --> 04:33:52,200 THERAPY TO TOLERATE INFECTIONS, 5992 04:33:52,200 --> 04:33:54,040 ET CETERA, MIGHT HAVE BEEN A 5993 04:33:54,040 --> 04:33:56,880 KWER AND WE HAVE RELEVANT 5994 04:33:56,880 --> 04:33:58,520 RETROSPECTIVE DATA TO SUPPORT 5995 04:33:58,520 --> 04:34:01,000 THIS AND COVERED EUROPEAN 5996 04:34:01,000 --> 04:34:04,280 PROPERTY OF GROUPS DATA THAT WE 5997 04:34:04,280 --> 04:34:06,760 PUBLISHED IN LANCET HEEM ATOLOGY 5998 04:34:06,760 --> 04:34:08,960 LAST YEAR AND GOT DATA FROM 5999 04:34:08,960 --> 04:34:12,480 CORINNE'S DATA FROM SORRY 6000 04:34:12,480 --> 04:34:14,720 COLLEEN'S DATA FROM PLATEAU 2 6001 04:34:14,720 --> 04:34:16,760 AND 5 TREATING PATIENTS WITH 6002 04:34:16,760 --> 04:34:19,320 INFANT ALL AND PRESENTED DATA 6003 04:34:19,320 --> 04:34:21,440 FROM COHORT THAT IS LOOKING AT 6004 04:34:21,440 --> 04:34:25,000 14 INFANTS THEY HAD IN THEIR 6005 04:34:25,000 --> 04:34:27,360 STUDY. IF WE LOOK AT 6006 04:34:27,360 --> 04:34:28,680 MANUFACTURING FEASIBILITY, 6007 04:34:28,680 --> 04:34:30,560 PROPORTION OF PATIENTS DIDN'T GO 6008 04:34:30,560 --> 04:34:32,920 ON TO HAVE PRODUCT INFUSED 6009 04:34:32,920 --> 04:34:34,320 BECAUSE OF PROGRESSIVE DISEASE 6010 04:34:34,320 --> 04:34:36,880 RATES OF NEGATIVE CR AND 6 AND 6011 04:34:36,880 --> 04:34:40,720 12 MONTH SURVIVAL AND OVERALL 6012 04:34:40,720 --> 04:34:41,880 SURVIVAL AND COMPARING TO 6013 04:34:41,880 --> 04:34:44,240 OUTCOMES IN RED AND LOOKING AT 6014 04:34:44,240 --> 04:34:45,600 OUTCOMES FROM APPLICATION AND 6015 04:34:45,600 --> 04:34:48,400 BOLDED STUDIES AND COLLEEN'S 6016 04:34:48,400 --> 04:34:50,760 DATA WITH PLATEAU 2 AND PLATEAU 6017 04:34:50,760 --> 04:34:54,640 5 YOU CAN SEE DELIVERABILITY AND 6018 04:34:54,640 --> 04:34:57,240 THE SHORT-TERM OUTCOMES IN TERMS 6019 04:34:57,240 --> 04:35:00,080 OF RESPONSE RATES AND LONG-TERM 6020 04:35:00,080 --> 04:35:01,520 OUTCOMES ARE FAVORABLE FOR 6021 04:35:01,520 --> 04:35:04,400 COHORT OF PATIENTS CONSIDERED AS 6022 04:35:04,400 --> 04:35:06,600 HAVING AGGRESSIVE DISEASE DIDN'T 6023 04:35:06,600 --> 04:35:08,680 RESPOND TO THERAPY AND HAS POOR 6024 04:35:08,680 --> 04:35:11,320 PROGNOSIS IN MOST CONTEXTS AND 6025 04:35:11,320 --> 04:35:13,320 LOOKING AT DETAIL IN DATA THAT 6026 04:35:13,320 --> 04:35:16,880 WE ARE ABLE TO PROVIDE WITH SOME 6027 04:35:16,880 --> 04:35:19,080 GRANULARITY AND WE ARE LOOKING 6028 04:35:19,080 --> 04:35:21,520 IN EUROPE OF 15 CENTERS AND 6029 04:35:21,520 --> 04:35:24,040 LOOKED AT ALL DATA AROUND 6030 04:35:24,040 --> 04:35:25,360 CHILDREN SCREENED AT ANL LESS 6031 04:35:25,360 --> 04:35:29,680 THAN 3 YEARS THAT IS HEAVY 6032 04:35:29,680 --> 04:35:31,560 PREDOMINATED BY COHORT AND 6033 04:35:31,560 --> 04:35:33,800 COHORT IS 5 MONTHS AND MEDIAN 6034 04:35:33,800 --> 04:35:36,720 AGE INFUSION IS 17 MONTHS AND 6035 04:35:36,720 --> 04:35:39,800 REARRANGED 80% CAUSING TO INFANT 6036 04:35:39,800 --> 04:35:41,520 PROTOCOLS AND MAJORITY HAVE HAD 6037 04:35:41,520 --> 04:35:43,760 IT PRICED IN STEM CELL 6038 04:35:43,760 --> 04:35:45,600 TRANSPLANT AND MEDIAN OF TWO 6039 04:35:45,600 --> 04:35:47,000 LINES OF THERAPY NOT INCLUDING 6040 04:35:47,000 --> 04:35:49,840 TRANCE PLANTS HEAVILY PRETREATED 6041 04:35:49,840 --> 04:35:51,840 PATIENTS DEFINITELY RELEVANT TO 6042 04:35:51,840 --> 04:35:55,560 INFANT CONTEXT AND DATA WE GOT 6043 04:35:55,560 --> 04:35:57,800 ON LEUKO FORESIS PROJECTS THAT 6044 04:35:57,800 --> 04:36:01,120 ARE IN 38 PATIENTS YOU CAN SEE 6045 04:36:01,120 --> 04:36:02,680 VAST MAJORITY OF PATIENTS 6046 04:36:02,680 --> 04:36:04,720 COLLECTED WITH SINGLE DAY 6047 04:36:04,720 --> 04:36:06,840 HARVEST AND PATIENTS REQUIRE 6048 04:36:06,840 --> 04:36:09,560 MORE DAYS THAN THAT WORTH 6049 04:36:09,560 --> 04:36:11,120 CONSIDERING ACHIEVING AND 35 OUT 6050 04:36:11,120 --> 04:36:13,760 OF 38 PATIENTS AND CONCERNS 6051 04:36:13,760 --> 04:36:16,720 WHETHER CELLS ACTIVATE THAT WAY 6052 04:36:16,720 --> 04:36:19,440 AND ARE TRANCE DEUCEABLE NOT 6053 04:36:19,440 --> 04:36:20,560 BORN OUT AND [INDISCERNIBLE] 6054 04:36:20,560 --> 04:36:24,160 GENERATED WAS IN MEETING OF CAR 6055 04:36:24,160 --> 04:36:25,440 T-CELLS EXPECTED FROM OLDER 6056 04:36:25,440 --> 04:36:26,920 COHORT AS WELL AND FEASIBILITY 6057 04:36:26,920 --> 04:36:30,240 OF LEUKO FORESIS AND OF 6058 04:36:30,240 --> 04:36:32,080 MANUFACTURER IS NOT AN ISSUE AT 6059 04:36:32,080 --> 04:36:34,400 ALL AND WE HAVE OVERALL SURVIVAL 6060 04:36:34,400 --> 04:36:37,880 ON LEFT AND EVENT FREE SURVIVAL 6061 04:36:37,880 --> 04:36:39,920 CRITERIA ON THE RIGHT AND WE HAD 6062 04:36:39,920 --> 04:36:42,960 RELAPSES AND WE DIDN'T HAVE ANY 6063 04:36:42,960 --> 04:36:44,840 INCIDENCE OF LINEAGE SWITCH 6064 04:36:44,840 --> 04:36:47,320 WITHIN CONTEXT OF FOLLOW UP FOR 6065 04:36:47,320 --> 04:36:49,240 PAPER AFTER DATA CUTOFF FOR 6066 04:36:49,240 --> 04:36:51,760 PAPER ONE CASE CONFINED WITH 6067 04:36:51,760 --> 04:36:53,840 LINEAGE SWITCH AND FURTHER CASE 6068 04:36:53,840 --> 04:36:58,200 LOSS CD19 EXPRESSION AND MARKERS 6069 04:36:58,200 --> 04:37:01,920 AND RETAINED SOME LYMPHO MARKERS 6070 04:37:01,920 --> 04:37:03,680 TOO WASN'T TRUE AND LINEAGE 6071 04:37:03,680 --> 04:37:06,600 SWITCH AND KINETICS FROM 6072 04:37:06,600 --> 04:37:08,600 PROGRESSION AND TWO POSSIBLE 6073 04:37:08,600 --> 04:37:09,800 LINEAGE SWITCHES AFTER DATA 6074 04:37:09,800 --> 04:37:11,560 CUTOFF AND IN CONTEXT OF FOLLOW 6075 04:37:11,560 --> 04:37:13,960 UP WE HAD THERE WERE NONE ON THE 6076 04:37:13,960 --> 04:37:16,400 STUDY AS PUBLISHED. 6077 04:37:16,400 --> 04:37:19,280 SO, THERE WERE 8 PATIENTS WITH 6078 04:37:19,280 --> 04:37:21,400 RELAPSE AND 19 POSITIVE TO 6079 04:37:21,400 --> 04:37:24,440 DISEASE AND ONE WITH MIXED 6080 04:37:24,440 --> 04:37:25,880 [INDISCERNIBLE] DISEASE AND 6 6081 04:37:25,880 --> 04:37:27,920 PATIENTS WENT ON TO HAVE FURTHER 6082 04:37:27,920 --> 04:37:28,920 THERAPY BEFORE RELAPSE. 6083 04:37:28,920 --> 04:37:31,920 WE LOOKED AT A MORE STRINGENT 6084 04:37:31,920 --> 04:37:33,640 EVENT DEFINITION WE INCORPORATED 6085 04:37:33,640 --> 04:37:36,840 EVENTS RELATED TO EMERGENCE OF 6086 04:37:36,840 --> 04:37:39,880 NID AND APPLICATION TO FURTHER 6087 04:37:39,880 --> 04:37:41,880 LEUK EMO THERAPY AND SURVIVAL 6088 04:37:41,880 --> 04:37:45,240 SHOWN HERE IF YOU LIKE THIS IS 6089 04:37:45,240 --> 04:37:46,320 PERHAPS CLINICALLY MORE RELEVANT 6090 04:37:46,320 --> 04:37:47,880 EVENT DEFINITIONS AND POINT OF 6091 04:37:47,880 --> 04:37:49,320 VIEW AND SCREENING AND TELLING 6092 04:37:49,320 --> 04:37:52,400 THEM WHAT IS LIKELIHOOD NEEDING 6093 04:37:52,400 --> 04:37:55,360 THERAPY BEING LEUKEMIA FREE AND 6094 04:37:55,360 --> 04:37:56,920 NOT ANY OTHER THERAPY AND 6095 04:37:56,920 --> 04:37:58,080 PARAMETERS I LIKE TO DISCUSS 6096 04:37:58,080 --> 04:38:00,840 WITH PATIENTS IN CONTEXT WE HAVE 6097 04:38:00,840 --> 04:38:03,400 TWO ADDITIONAL CASES OF 6098 04:38:03,400 --> 04:38:05,480 EMERGENTS BOTH WENT ON TO 6099 04:38:05,480 --> 04:38:07,520 FURTHERTHERAPY AND ONE WAS CD19 6100 04:38:07,520 --> 04:38:11,600 NEGATIVE AND ONE WAS CD19 6101 04:38:11,600 --> 04:38:12,560 POSITIVE AND ONGOING 6102 04:38:12,560 --> 04:38:15,160 [INDISCERNIBLE] AND CURVES 6103 04:38:15,160 --> 04:38:16,320 OVERLAY DATA. 6104 04:38:16,320 --> 04:38:19,760 IN TERMS OF TOXICITIES RATES OF 6105 04:38:19,760 --> 04:38:22,640 SEVERE CYTOKINE SYNDROME WERE 6106 04:38:22,640 --> 04:38:25,200 LESS SEEN ON THIS AND REAL WORLD 6107 04:38:25,200 --> 04:38:27,200 DATA POINTING TO FACT WE BRIDGE 6108 04:38:27,200 --> 04:38:29,760 MORE EFFECTIVELY REDUCING RISK 6109 04:38:29,760 --> 04:38:33,840 OF SEVERE CRS AND ICANS EKWIF 6110 04:38:33,840 --> 04:38:38,840 TLOENT RATE OF ELLI ANA STUDY 6111 04:38:38,840 --> 04:38:40,400 AND SLIGHT INSTANCE OF 6112 04:38:40,400 --> 04:38:44,240 DIFFERENCE OF CRYTOPENIAS AND IN 6113 04:38:44,240 --> 04:38:47,000 TERMS OF FEASIBILITY DELIVERY IN 6114 04:38:47,000 --> 04:38:49,920 TOXICITY PROFILE IS SIMILAR TO 6115 04:38:49,920 --> 04:38:53,400 OLDER PATIENTS AND TOXICITY TO 6116 04:38:53,400 --> 04:38:55,880 BE TAKEN INTO ACCOUNT AND 6117 04:38:55,880 --> 04:38:57,600 FEASIBILITY FOR DELIVERY OF 6118 04:38:57,600 --> 04:38:59,000 YOUNGER CHILD IS SIMILAR TO THAT 6119 04:38:59,000 --> 04:39:00,840 AND OLDER CHILDREN RESPONSE RATE 6120 04:39:00,840 --> 04:39:03,080 LONGER OUTCOMES TOXICITY RATES 6121 04:39:03,080 --> 04:39:06,480 SAME FOR CHILDREN IN TERMS OF 6122 04:39:06,480 --> 04:39:10,880 GRANULARITY FOR PATIENTS 15 OUT 6123 04:39:10,880 --> 04:39:14,240 OF 35 TREATED DID GO ON TO 6124 04:39:14,240 --> 04:39:19,960 THERAPY AND [INDISCERNIBLE] 2 6125 04:39:19,960 --> 04:39:24,400 PATIENTS HAD GONE ON TO HAVE 6126 04:39:24,400 --> 04:39:25,600 TRANSPLANT BECAUSE OF PHYSICIAN 6127 04:39:25,600 --> 04:39:27,960 PREFERENCE ALONE AND WITH THIS 6128 04:39:27,960 --> 04:39:31,800 TO WRAP UP THANKING COLLEAGUES 6129 04:39:31,800 --> 04:39:37,160 PROVIDING DATA FOR 6130 04:39:37,160 --> 04:39:42,080 [INDISCERNIBLE]. THANK YOU. 6131 04:39:42,080 --> 04:39:48,040 >> NEXT STOP IS DR. LEAHY WHO 6132 04:39:48,040 --> 04:39:58,000 WILL TALK ABOUT CYTOGENETICS. 6133 04:39:58,000 --> 04:40:01,640 >> ALL RIGHT. HI, EVERYONE. 6134 04:40:01,640 --> 04:40:04,040 I'M ALLIE LEAHY AND HAVE NO 6135 04:40:04,040 --> 04:40:06,040 CONFLICTS AND SLIDE WILL BE 6136 04:40:06,040 --> 04:40:08,360 FAMILIAR TO EVERYONE. ON LEFT 6137 04:40:08,360 --> 04:40:10,200 IS AGE DISTRIBUTION OF COMMON 6138 04:40:10,200 --> 04:40:13,600 GENETIC ABHORATIONS WE FIND IN 6139 04:40:13,600 --> 04:40:16,720 LEUKEMIA IN AVERIENT SETTING AND 6140 04:40:16,720 --> 04:40:17,440 RIGHT-HAND SIDE OF THE SCREEN 6141 04:40:17,440 --> 04:40:20,120 YOU SEE LIST OF CYTOGENETICS 6142 04:40:20,120 --> 04:40:22,280 USED TO RISK STRATIFY IN UPFRONT 6143 04:40:22,280 --> 04:40:24,840 SETTING IN DIAGNOSIS IN NATIONAL 6144 04:40:24,840 --> 04:40:29,080 AND INTERNATIONAL CONSORTIUM. 6145 04:40:29,080 --> 04:40:31,800 CRYTOGENETIC AND OTHER MOLECULAR 6146 04:40:31,800 --> 04:40:35,400 GENOMIC AB-HARRATIONS ARE KNOWN 6147 04:40:35,400 --> 04:40:37,200 TO HAVE PROGNOSTIC DIAGNOSIS AND 6148 04:40:37,200 --> 04:40:40,000 RISK ASSESSMENT IS CARRIED 6149 04:40:40,000 --> 04:40:42,040 THROUGH TO RELAPSE AND 6150 04:40:42,040 --> 04:40:43,440 SIGNIFICANCE OF DIFFERENT RISK 6151 04:40:43,440 --> 04:40:45,600 CATEGORIES ARE SORT OF AN OPEN 6152 04:40:45,600 --> 04:40:48,880 QUESTION IN THE USE OF CAR 6153 04:40:48,880 --> 04:40:52,000 T-CELL THERAPY. I WILL FIRST 6154 04:40:52,000 --> 04:40:53,240 TALK THROUGH GENERAL FINDINGS 6155 04:40:53,240 --> 04:40:55,360 WHEN WE DO WHAT WE HAVE TO DO IN 6156 04:40:55,360 --> 04:40:58,880 CAR T-CELL WORLD THAT IS LUMP 6157 04:40:58,880 --> 04:41:00,760 AND SPLIT IN AWKWARD CATEGORIES 6158 04:41:00,760 --> 04:41:04,720 AND IS WORK WE DID AT CHOC WITH 6159 04:41:04,720 --> 04:41:07,760 RETROSPECTIVE ANALYSIS WITH 231 6160 04:41:07,760 --> 04:41:11,240 CAR NAÏVE PATIENTS WITH WHOM WE 6161 04:41:11,240 --> 04:41:14,120 HAVE ROBUST CRYTOGENETIC AND 6162 04:41:14,120 --> 04:41:17,160 MOLECULAR GENETIC DIAGNOSIS OR 6163 04:41:17,160 --> 04:41:20,000 FROM RECENT RELAPSE AND RELAPSED 6164 04:41:20,000 --> 04:41:23,080 REFRACTORY CD19 POSITIVE DISEASE 6165 04:41:23,080 --> 04:41:25,720 TREATED ON 5 CLINICAL TRIALS 6166 04:41:25,720 --> 04:41:29,000 [INDISCERNIBLE] CONSTRUCT OR 6167 04:41:29,000 --> 04:41:33,480 HUMANIZED CONSTRUCT OR 6168 04:41:33,480 --> 04:41:34,520 COMMERCIALIZED CHIMERA AND BROKE 6169 04:41:34,520 --> 04:41:37,280 TO FOUR CATEGORIES HIGH RISK 6170 04:41:37,280 --> 04:41:39,840 THAT WE KNOW AND LOVE AND 6171 04:41:39,840 --> 04:41:43,200 INTERMEDIATE RISK STRATIFICATION 6172 04:41:43,200 --> 04:41:44,200 ACROSS THE UNITED STATES AND 6173 04:41:44,200 --> 04:41:47,080 EUROPEAN TRIALS AND FAVORABLE 6174 04:41:47,080 --> 04:41:49,400 GENETICS AND UNINFORMATIVE THAT 6175 04:41:49,400 --> 04:41:51,800 I THINK I WILL HAVE YOU HOLD ON 6176 04:41:51,800 --> 04:41:54,200 TO AND COME BACK LATER IN THE 6177 04:41:54,200 --> 04:41:55,480 DISCUSSION. THEY WERE THINGS 6178 04:41:55,480 --> 04:41:57,600 NOT NECESSARILY THAT COULD BE 6179 04:41:57,600 --> 04:41:59,880 NORMAL BUT COULD LUMP TOGETHER 6180 04:41:59,880 --> 04:42:03,640 COMPLEX CYTOGENETICS AND 6181 04:42:03,640 --> 04:42:05,440 OTHERWISE UNBUCKETABLE LESIONS. 6182 04:42:05,440 --> 04:42:11,920 LOOKING AT THIS WITH LENS OF DO 6183 04:42:11,920 --> 04:42:13,960 CYTOGENETICS DRIVE OUTCOMES 6184 04:42:13,960 --> 04:42:16,160 ANSWER WAS ENCOURAGING BROKE 6185 04:42:16,160 --> 04:42:18,320 DOWN BY FOUR BIG RISK CATEGORIES 6186 04:42:18,320 --> 04:42:21,680 SEEING FOR RFS OR ROS THAT WAS A 6187 04:42:21,680 --> 04:42:23,880 NEGATIVE FINDING AND DID 6188 04:42:23,880 --> 04:42:27,360 SUBANALYSIS LOOKING AT PH AND 6189 04:42:27,360 --> 04:42:30,240 PHLIKE AND KMT2A AND 6190 04:42:30,240 --> 04:42:33,080 SPECIFICALLY IN INFANTS PH AND 6191 04:42:33,080 --> 04:42:36,240 PHLIKE SIMILAR TO LARGE LUMP 6192 04:42:36,240 --> 04:42:37,240 FINDINGS AND NO DIFFERENCE 6193 04:42:37,240 --> 04:42:40,760 COMPARED TO OTHERS AND KM22AS I 6194 04:42:40,760 --> 04:42:44,080 WILL TALK ABOUT IN A SECOND AND 6195 04:42:44,080 --> 04:42:46,520 WE LOOKED AT MORPH FOE LOGIC 6196 04:42:46,520 --> 04:42:48,560 RELAPSE AND CLINICALLY 6197 04:42:48,560 --> 04:42:50,720 APPLICABLE MRD RELAPSE AND IN 6198 04:42:50,720 --> 04:42:54,040 CASE OF ANALYSIS THERE WAS NO 6199 04:42:54,040 --> 04:42:56,680 DITCHES USING RELAPSE IN EVENT 6200 04:42:56,680 --> 04:42:59,480 OF RELAPSE FREE SURVIVAL. THIS 6201 04:42:59,480 --> 04:43:03,000 WAS BUTT TRESSED BY 6202 04:43:03,000 --> 04:43:04,200 MULTIVARIABLE MODELS TAKING INTO 6203 04:43:04,200 --> 04:43:07,520 ACCOUNT THINGS LIKE DISEASE 6204 04:43:07,520 --> 04:43:10,680 BURDEN AT INFUSION. 6205 04:43:10,680 --> 04:43:14,560 LOOKING AT OTHER STUDIES WE 6206 04:43:14,560 --> 04:43:16,680 TALKED ABOUT STUDY A PARTICULAR 6207 04:43:16,680 --> 04:43:18,680 STUDY AND MULTICENTER CONSTRUCT 6208 04:43:18,680 --> 04:43:22,680 LOOKING AT 41BB CARS AND CD28 6209 04:43:22,680 --> 04:43:24,560 CARS AND THIS DID PULL A 6210 04:43:24,560 --> 04:43:26,360 PORTIONING OF PATIENTS FROM 6211 04:43:26,360 --> 04:43:28,800 PREVIOUS ANALYSIS TO THIS 6212 04:43:28,800 --> 04:43:31,160 ANALYSIS AND DUPLICATIVE PATIENT 6213 04:43:31,160 --> 04:43:34,280 INVOLVEMENT BROKE DOWN 6214 04:43:34,280 --> 04:43:35,560 CYTOGENETICS TO MORE BARE 6215 04:43:35,560 --> 04:43:37,200 DESCRIPTION THAN WHAT WAS 6216 04:43:37,200 --> 04:43:39,480 INCLUDED IN PREVIOUS DISCUSSION 6217 04:43:39,480 --> 04:43:41,840 AND WASN'T THE INTENDED ANALYSIS 6218 04:43:41,840 --> 04:43:46,720 IN THIS PAPER THAT ARE PURELY 6219 04:43:46,720 --> 04:43:49,600 DESCRIPTIVE CAP LYNNE MEYER 6220 04:43:49,600 --> 04:43:53,720 CURVES I WILL SHOW YOU HERE 6221 04:43:53,720 --> 04:43:55,760 UNIVARIATE ANALYSIS AND CAUTION 6222 04:43:55,760 --> 04:43:56,800 WITH CONCLUSIONS AND 6223 04:43:56,800 --> 04:43:58,560 ILLUSTRATING FROM THIS LOWER 6224 04:43:58,560 --> 04:44:01,800 LINE OF HYPODIPLOID PATIENTS IT 6225 04:44:01,800 --> 04:44:03,920 THAT IS A ROBUST GROUP OF 6226 04:44:03,920 --> 04:44:09,800 PATIENTS 380 WITH KNOWN GENETIC 6227 04:44:09,800 --> 04:44:10,920 CHARACTERISTICS AND THIS GROUP 6228 04:44:10,920 --> 04:44:12,360 OF 14 IS LARGE FOR NUMBERS THAT 6229 04:44:12,360 --> 04:44:15,240 WE KNOW WE HAVE IN THE WORLD. 6230 04:44:15,240 --> 04:44:17,560 THIS IS REDEMONSTRATED WHEN 6231 04:44:17,560 --> 04:44:19,720 BROKEN DOWN EVEN FURTHER THAT 6232 04:44:19,720 --> 04:44:22,480 LOWEST FOUR LINES ARE 6233 04:44:22,480 --> 04:44:27,920 HYPODIPLOID THAT CATEGORY OF 6234 04:44:27,920 --> 04:44:33,080 WHAT I WANTED YOU TO HOLD ON TO 6235 04:44:33,080 --> 04:44:36,520 NORMAL ETV6 RUNG AND YOU HAVE TO 6236 04:44:36,520 --> 04:44:38,320 LIMIT CONCLUSIONS TO DRAW FROM 6237 04:44:38,320 --> 04:44:39,840 THIS AND DEFINITELY INDICATES 6238 04:44:39,840 --> 04:44:43,280 THERE IS MORE TO PULL OUT FROM 6239 04:44:43,280 --> 04:44:48,480 THE POPULATIONS ADAM TALKED 6240 04:44:48,480 --> 04:44:49,600 ABOUT THIS EARLIER AND THOUGHT 6241 04:44:49,600 --> 04:44:52,400 IT WAS INTERESTING AND PULLING 6242 04:44:52,400 --> 04:44:56,760 ON THIS SAME KARMA CO-HORT 380 6243 04:44:56,760 --> 04:45:00,000 PATIENTS WITH CHARACTERISTICS 6244 04:45:00,000 --> 04:45:03,600 WHITTLED DOWN TO 170-ISH THAT 6245 04:45:03,600 --> 04:45:04,960 HAD CYTOGENETICS THAT RELAPSED 6246 04:45:04,960 --> 04:45:07,560 AND LOOKING AT DIFFERENCE IN 6247 04:45:07,560 --> 04:45:10,280 CYTOGENETICS WITH ASSOCIATION TO 6248 04:45:10,280 --> 04:45:12,280 RELAPSED PHENOTYPE AND HE 6249 04:45:12,280 --> 04:45:14,440 DISCUSSED THERE WAS NOT -- MOST 6250 04:45:14,440 --> 04:45:17,600 THINGS FELL OUT IN MOVE FROM 6251 04:45:17,600 --> 04:45:19,640 UNIVARIATE TO MULTIVARIATE 6252 04:45:19,640 --> 04:45:21,200 ANALYSIS AND CAPTURED TWO THINGS 6253 04:45:21,200 --> 04:45:23,960 HE DISCUSSED IN K2M STATUS THAT 6254 04:45:23,960 --> 04:45:27,160 WAS ONLY THING ASSOCIATED WITH 6255 04:45:27,160 --> 04:45:31,600 ANY RELAPSED PHENOTYPE AND 6256 04:45:31,600 --> 04:45:34,800 PREDOMINANTLY WAS ONLY QUITE 6257 04:45:34,800 --> 04:45:38,440 STRONG ASSOCIATION SEEN IN 6258 04:45:38,440 --> 04:45:40,000 PATIENTS WITH LINEAGE SWITCH AND 6259 04:45:40,000 --> 04:45:43,360 NICE SEGUE TO KM2A 6260 04:45:43,360 --> 04:45:44,680 REARRANGEMENTS AND WHAT WE KNOW 6261 04:45:44,680 --> 04:45:47,120 ABOUT THEM SPECIFICALLY AND THIS 6262 04:45:47,120 --> 04:45:51,680 IS ADAMS WORK AND WORK FROM CHOC 6263 04:45:51,680 --> 04:45:54,080 SIDE BY SIDE AND SEE HERE 6264 04:45:54,080 --> 04:45:56,760 RELAPSE FREE SURVIVAL KMT2A 6265 04:45:56,760 --> 04:46:00,240 GROUP REPLICATES WHAT WE SAW IN 6266 04:46:00,240 --> 04:46:03,640 LARGER LUMPED ANALYSIS AND NO 6267 04:46:03,640 --> 04:46:04,920 STATISTICAL DIFFERENCE BETWEEN 6268 04:46:04,920 --> 04:46:08,240 THOSE WITH KM2TA ARRANGEMENTS 6269 04:46:08,240 --> 04:46:13,280 AND THOSE WITH CRYTOGENETIC 6270 04:46:13,280 --> 04:46:14,360 CHARACTERISTICS AND TREND FOR 6271 04:46:14,360 --> 04:46:16,240 SIGNIFICANCE AND MULTIVARIABLE 6272 04:46:16,240 --> 04:46:19,720 MODEL CONTROLLING FOR KEY 6273 04:46:19,720 --> 04:46:20,320 CHARACTERISTICS THAT DIDN'T 6274 04:46:20,320 --> 04:46:21,640 REACH STATISTICAL SIGNIFICANCE 6275 04:46:21,640 --> 04:46:25,520 AND WE NEED LARGER SAMPLE SIZE 6276 04:46:25,520 --> 04:46:31,160 AND MORE EXPERIENCE WITH THIS 6277 04:46:31,160 --> 04:46:34,680 AND BEAUTIFUL ASSOCIATION WITH 6278 04:46:34,680 --> 04:46:36,760 LINEAGE SWITCH AND LOOKING AT 6279 04:46:36,760 --> 04:46:39,800 THIS STORY IS MORE DISMAL FOR 6280 04:46:39,800 --> 04:46:42,280 PATIENTS IN PART BECAUSE OF 6281 04:46:42,280 --> 04:46:43,120 LINEAGE SWITCH THERE WERE 6282 04:46:43,120 --> 04:46:45,360 SIGNIFICANT NUMBERS IN CO-HORTS 6283 04:46:45,360 --> 04:46:48,080 WITH OVERLAPPING PATIENTS AND 6284 04:46:48,080 --> 04:46:50,560 UNIFORMLY PATIENTS EXPERIENCING 6285 04:46:50,560 --> 04:46:52,000 LINEAGE SWITCH DIED FROM THEIR 6286 04:46:52,000 --> 04:46:53,760 DISEASE AND THESE PATIENTS THERE 6287 04:46:53,760 --> 04:46:55,760 DOESN'T SEEM TO BE SIGNIFICANTLY 6288 04:46:55,760 --> 04:47:01,560 INCREASED RISK OF RELANCEPSE AN 6289 04:47:01,560 --> 04:47:04,600 WHEN THEY DO IT IS DIFFICULT TO 6290 04:47:04,600 --> 04:47:06,880 SALVAGE AND WHO TO PAY THAT IS 6291 04:47:06,880 --> 04:47:10,880 AT HIGHER RISK OF RELAPSE AMIDST 6292 04:47:10,880 --> 04:47:14,520 PATIENTS AND WHAT WE CAN DO IN 6293 04:47:14,520 --> 04:47:21,080 POST CAR INFUSION. 6294 04:47:21,080 --> 04:47:28,320 LY PAUSE BRIEFLY IN THIS AND WE 6295 04:47:28,320 --> 04:47:32,440 LOOKED AT 13 PATIENTS DIAGNOSED 6296 04:47:32,440 --> 04:47:40,120 WITH INFANT LEUKEMIA AND KMT2 6297 04:47:40,120 --> 04:47:43,040 REARRANGEMENTS AND THERE IS 67% 6298 04:47:43,040 --> 04:47:50,720 RELAPSE FREE SURVIVAL AT 2 YEARS 6299 04:47:50,720 --> 04:47:55,240 THAT DAUNTING ASSOCIATION OF 6300 04:47:55,240 --> 04:47:58,520 SURVIVAL WITH 3.6 TIMES INCREASE 6301 04:47:58,520 --> 04:48:01,480 IN ALL CAUSE MORTGAGE ALET THAT 6302 04:48:01,480 --> 04:48:03,240 IS A SIGNIFICANT FINDING AND 6303 04:48:03,240 --> 04:48:05,880 MOVING TO POTENTIAL GENETICS OF 6304 04:48:05,880 --> 04:48:09,320 INTEREST. THERE ARE, AGAIN, 6305 04:48:09,320 --> 04:48:12,680 PULLING ON THAT OTHER 6306 04:48:12,680 --> 04:48:13,600 CRYTOGENETIC ABHORATION CATEGORY 6307 04:48:13,600 --> 04:48:15,680 THERE IS A NUMBER OF EMERGING 6308 04:48:15,680 --> 04:48:17,360 INTERESTING THINGS IN THE FIELD 6309 04:48:17,360 --> 04:48:19,520 THAT WE HAVE NOT YET STARTED TO 6310 04:48:19,520 --> 04:48:22,640 EVALUATE. THE WE HAVE SEEMINGLY 6311 04:48:22,640 --> 04:48:24,280 WHITTLED DOWN WHAT WE LOOKED AT 6312 04:48:24,280 --> 04:48:26,560 TO WHAT WE KNOW THAT DIAGNOSIS 6313 04:48:26,560 --> 04:48:28,760 IS IMPORTANT AND A GREAT 6314 04:48:28,760 --> 04:48:31,840 STARTING POINT AND TP53 6315 04:48:31,840 --> 04:48:32,520 ALTERATIONS THAT ARE RARE LIKE 6316 04:48:32,520 --> 04:48:34,280 MANY THINGS WE LOOK AT. THEY 6317 04:48:34,280 --> 04:48:38,520 ARE ASSOCIATED WITH HYPO 6318 04:48:38,520 --> 04:48:41,440 DIPLOIDY AND OLDER ANL AND 6319 04:48:41,440 --> 04:48:43,120 ARTICLES IN LYMPHOMA 6320 04:48:43,120 --> 04:48:46,280 INVESTIGATORS DEMONSTRATED THERE 6321 04:48:46,280 --> 04:48:49,280 IS CONCERN FOR DISREGULATION IN 6322 04:48:49,280 --> 04:48:51,800 PATHWAYS THAT CONTROL 6323 04:48:51,800 --> 04:48:53,720 CYTOTOXICITY OF CAR T-CELLS IN 6324 04:48:53,720 --> 04:48:56,320 FIRST ARTICLE THEY DEMONSTRATED 6325 04:48:56,320 --> 04:48:58,440 PATIENTS HAD INFERIOR OUTCOMES 6326 04:48:58,440 --> 04:49:02,120 IN SECOND ARTICLE THERE WAS SOME 6327 04:49:02,120 --> 04:49:05,080 DEMONSTRATION THAT IS USE OF 6328 04:49:05,080 --> 04:49:07,400 CRYTOBEEN AND SYNERGISTIC EFFECT 6329 04:49:07,400 --> 04:49:09,360 THAT MITIGATED THIS AND THINGS 6330 04:49:09,360 --> 04:49:11,800 TO THINK ABOUT GAINING MORE 6331 04:49:11,800 --> 04:49:13,200 INTEREST OR INFORMATION IN 6332 04:49:13,200 --> 04:49:16,040 GENOMIC FIELD AND THINKING ABOUT 6333 04:49:16,040 --> 04:49:18,920 WHAT WE WANT TO FOCUS ON FOR 6334 04:49:18,920 --> 04:49:22,200 ENRICHING PATIENT POPULATION 6335 04:49:22,200 --> 04:49:25,600 SAMPLE SIZES AND THESE ARE 6336 04:49:25,600 --> 04:49:28,120 SLIDES I STOLE FROM ANDRÉ'S 6337 04:49:28,120 --> 04:49:30,480 PRESENTATION AND OF PLANNING OF 6338 04:49:30,480 --> 04:49:32,320 CONFERENCE AND PLUG FOR 6339 04:49:32,320 --> 04:49:34,560 RETROSPECTIVE WORK THAT HE IS 6340 04:49:34,560 --> 04:49:36,680 INTERESTED IN DOING FOR TWO 6341 04:49:36,680 --> 04:49:40,800 RELATIVELY RARE LESIONS AND WE 6342 04:49:40,800 --> 04:49:42,760 KNOW HAVE QUESTIONABLE OUTCOMES 6343 04:49:42,760 --> 04:49:44,960 AND PUT TOGETHER A DELAYED GROUP 6344 04:49:44,960 --> 04:49:47,520 OF ALREADY PUBLISHED DATA IN 6345 04:49:47,520 --> 04:49:49,200 TERMS WHAT WE KNOW ABOUT 6346 04:49:49,200 --> 04:49:52,000 TRANSLOCATION 119 AND I ADDED 6347 04:49:52,000 --> 04:49:53,240 DETAILS INCLUDED IN WORK COMING 6348 04:49:53,240 --> 04:49:55,480 OUT OF CHOC TO THIS. 6349 04:49:55,480 --> 04:49:59,160 DEMONSTRATING THAT IN SORT OF 6350 04:49:59,160 --> 04:50:00,640 INTERNATIONAL LOOSE COHORT OF 30 6351 04:50:00,640 --> 04:50:04,720 WE HAVE 13 ALIVE AND 12 IN CR. 6352 04:50:04,720 --> 04:50:08,440 REALLY A RELATIVE POSTY OF 6353 04:50:08,440 --> 04:50:09,920 GRANULAR INFORMATION AROUND 6354 04:50:09,920 --> 04:50:10,960 PATIENTS THAT IS IMPORTANT TO 6355 04:50:10,960 --> 04:50:12,720 LOOK AT THAT AND DEFINITELY TO 6356 04:50:12,720 --> 04:50:17,400 LOOK AT 7 TAEN-19 AND LESION WE 6357 04:50:17,400 --> 04:50:18,440 KNOW HAS SIGNIFICANT 6358 04:50:18,440 --> 04:50:20,680 IMPLICATIONS FOR PATIENTS AND 6359 04:50:20,680 --> 04:50:23,160 AGAIN, RARE, TOTAL OF 15 6360 04:50:23,160 --> 04:50:25,600 PATIENTS 8 ALIVE AND POSSIBLE 8 6361 04:50:25,600 --> 04:50:32,320 IN CONTINUOUS CR AND ADD IING 6362 04:50:32,320 --> 04:50:33,520 HYPODIPLOIDY TO THIS AND DIDN'T 6363 04:50:33,520 --> 04:50:35,600 PULL DATA LIKE THIS AND GOING 6364 04:50:35,600 --> 04:50:38,240 FORWARD IN TERMS OF WHAT WE HAVE 6365 04:50:38,240 --> 04:50:41,440 SORT OF IN THE WORKS AND ALREADY 6366 04:50:41,440 --> 04:50:45,000 IN PROCESS AND ANDRÉ'S 119 AND 6367 04:50:45,000 --> 04:50:47,760 1719 I WOULD ARGUE FOR ADDITION 6368 04:50:47,760 --> 04:50:50,280 OF HYPODIPLOIDY COHORT AND 6369 04:50:50,280 --> 04:50:52,520 PROSPECTIVE TRIALS WE HAVE ONE 6370 04:50:52,520 --> 04:50:57,400 ONGOING PRIMARY INVESTIGATOR DEN 6371 04:50:57,400 --> 04:50:58,640 OVIA INSTITUTION AT CHOC AND 6372 04:50:58,640 --> 04:51:02,080 LOOKING AT LOCATIONS AND 6373 04:51:02,080 --> 04:51:04,040 HYPODIPLOIDY AS COHORT AND HIGH 6374 04:51:04,040 --> 04:51:07,360 RISKS K2A REARRANGEMENT OF 6375 04:51:07,360 --> 04:51:10,640 INFANTS AMONGST OTHERS. THANK 6376 04:51:10,640 --> 04:51:15,960 YOU. 6377 04:51:15,960 --> 04:51:16,760 >> [INDISCERNIBLE] FROM 6378 04:51:16,760 --> 04:51:18,240 CHILDREN'S HOSPITAL OF LA WILL 6379 04:51:18,240 --> 04:51:25,600 TALK ABOUT DRIVING CARS FORWARD. 6380 04:51:25,600 --> 04:51:28,600 >> >> THANK YOU, EVERYBODY. 6381 04:51:28,600 --> 04:51:39,080 THANK YOU ALL FOR STAYING. 6382 04:51:40,360 --> 04:51:44,080 >> WE KNOW THERE IS LIMITED 6383 04:51:44,080 --> 04:51:46,960 APPROVAL OF CAR T-CELL THERAPY 6384 04:51:46,960 --> 04:51:51,160 FOR PEDIATRICS TO DATE AND 2017 6385 04:51:51,160 --> 04:51:51,800 [INDISCERNIBLE] AND INDICATION 6386 04:51:51,800 --> 04:51:55,480 IS BALL IN SECOND OR LATER 6387 04:51:55,480 --> 04:51:57,800 RELAPSE AND LOOSE DEFINITION OF 6388 04:51:57,800 --> 04:51:59,720 REFRACTORY OR HOWEVER YOU WANT 6389 04:51:59,720 --> 04:52:01,280 TO INTERPRET IT FOLLOWING 6390 04:52:01,280 --> 04:52:05,600 MULTIPLE TRIALS OF DEMONSTRATED 6391 04:52:05,600 --> 04:52:07,320 EFFICACY AND SUBSETS THAT WE 6392 04:52:07,320 --> 04:52:10,640 HEARD ABOUT IN THIS SESSION AND 6393 04:52:10,640 --> 04:52:11,920 DOWNSTREAM INFANTS FIRST RELAPSE 6394 04:52:11,920 --> 04:52:16,200 AND LACK OF INDUSTRY SUPPORTER 6395 04:52:16,200 --> 04:52:17,480 REGISTRATIONS IN PEDIATRIC 6396 04:52:17,480 --> 04:52:19,840 INDICATIONS AND FOCUS ON FIRST 6397 04:52:19,840 --> 04:52:22,040 RELAPSE IN THIS TALK THAT ARE 6398 04:52:22,040 --> 04:52:23,960 PRIMARILY BONE MARROW AND CNS 6399 04:52:23,960 --> 04:52:25,960 AND FIRST RELAPSE IS CURRENTLY 6400 04:52:25,960 --> 04:52:28,120 NO. 1 UNMET NEED IN ALL. THERE 6401 04:52:28,120 --> 04:52:30,640 IS A LOT OF PATIENTS BECAUSE OF 6402 04:52:30,640 --> 04:52:32,640 THE SHEER NUMBERS IS ONE OF THE 6403 04:52:32,640 --> 04:52:37,680 MOST COMMON CANCERS RELAPSED ALL 6404 04:52:37,680 --> 04:52:39,680 AND THERAPY FOR MOST IS INTENSE 6405 04:52:39,680 --> 04:52:41,680 AND THERAPY OUTCOME IS DISMAL 6406 04:52:41,680 --> 04:52:44,480 AND PATIENTS RELAPSING EARLY 6407 04:52:44,480 --> 04:52:46,680 WITHIN 36 MONTHS AND THAT DON'T 6408 04:52:46,680 --> 04:52:48,680 RESPOND TO FIRST REDUCTION 6409 04:52:48,680 --> 04:52:50,560 CHEMOBLOCK AND STANDARD OF CARE 6410 04:52:50,560 --> 04:52:51,960 CURRENTLY FOR PATIENTS IN THE 6411 04:52:51,960 --> 04:52:55,320 UNITED STATES AFTER THE ALL1331 6412 04:52:55,320 --> 04:52:57,160 RESULTS THAT WERE PUBLISHED AND 6413 04:52:57,160 --> 04:52:59,560 CURRENT STANDARD OF CARE IS 6414 04:52:59,560 --> 04:53:01,600 REDUCTION OF CHEMOFOLLOWED BY 6415 04:53:01,600 --> 04:53:04,720 THIS FOLLOWED BY TRANSPLANT AND 6416 04:53:04,720 --> 04:53:07,360 THIS SURVIVAL IS 54% OF TUMOR 6417 04:53:07,360 --> 04:53:09,600 MAP OF THIS STUDY AND THERAPY 6418 04:53:09,600 --> 04:53:12,040 WAS TOXIC AND 4% TREATMENT 6419 04:53:12,040 --> 04:53:15,320 RELATED MORTALITY AND 43% RATED 6420 04:53:15,320 --> 04:53:18,920 3 TO 4 INFECTIONS AND DESPITE 6421 04:53:18,920 --> 04:53:22,280 TOXICITY 75% OF PATIENTS 6422 04:53:22,280 --> 04:53:23,720 REMAINED POSITIVE AFTER THIS 6423 04:53:23,720 --> 04:53:25,480 REINDUCTION CHEMO. WHAT IS 6424 04:53:25,480 --> 04:53:28,960 IMPORTANT IS 40% OF PATIENTS 6425 04:53:28,960 --> 04:53:30,200 DIDN'T PROCEED TO THIS AND 6426 04:53:30,200 --> 04:53:32,160 DIDN'T GET THROUGH THE FIRST 6427 04:53:32,160 --> 04:53:35,320 BLOCK OF CHEMOTHERAPY 6428 04:53:35,320 --> 04:53:38,880 SUCCESSFULLY TO GET TO BLINA AND 6429 04:53:38,880 --> 04:53:41,000 INTEND TO TREAT ANALYSIS ON 6430 04:53:41,000 --> 04:53:43,440 PATIENTS ON STUDY AND THIS EFS 6431 04:53:43,440 --> 04:53:47,680 IS 25% AND TAKING OUT PATIENTS 6432 04:53:47,680 --> 04:53:50,000 ENROLLING ON THE [INDISCERNIBLE] 6433 04:53:50,000 --> 04:53:53,120 THAT IS [INDISCERNIBLE] IT IS 6434 04:53:53,120 --> 04:53:56,360 STILL ONLY 30%. WHAT IS IDEAL 6435 04:53:56,360 --> 04:53:58,360 THERAPY OF HIGH RISK RELAPSE? 6436 04:53:58,360 --> 04:54:01,320 AVOID INFECTIONS AND ORGAN 6437 04:54:01,320 --> 04:54:05,600 DAMAGE AND WE KNOW CD19 CAR T 6438 04:54:05,600 --> 04:54:10,000 CAN DO THAT AND USING THIS AS A 6439 04:54:10,000 --> 04:54:11,880 STANDALONE VERSUS PERSISTENCE 6440 04:54:11,880 --> 04:54:13,720 AND WE DISCUSSED THIS THAT IS TO 6441 04:54:13,720 --> 04:54:16,440 BE DETERMINED AND 2EFS AND WHAT 6442 04:54:16,440 --> 04:54:19,240 WE HAVE HEARD ALL DAY IS ABOUT 6443 04:54:19,240 --> 04:54:22,040 50% OF MULTIPLY RELAPSED ALL AND 6444 04:54:22,040 --> 04:54:23,560 ANTICIPATE THIS IS BETTER IN 6445 04:54:23,560 --> 04:54:26,040 FIRST RELAPSE AND LOOKING AT 6446 04:54:26,040 --> 04:54:27,720 DATA ON PREVIOUS SLIDE 30% TO 6447 04:54:27,720 --> 04:54:31,200 IMPROVE TO 50% IS A BIG WIN AND 6448 04:54:31,200 --> 04:54:33,480 LOTS OF PATIENTS AND SWITCHING 6449 04:54:33,480 --> 04:54:36,680 GEARS A LITTLE TO ISOLATED CNS 6450 04:54:36,680 --> 04:54:38,720 RELAPSE AND UNMET NEEDS AND HERE 6451 04:54:38,720 --> 04:54:42,000 WE TALK ABOUT THE DATE ISOLATED 6452 04:54:42,000 --> 04:54:44,200 EXTRA MEDULLARY RELAPSE AND 18 6453 04:54:44,200 --> 04:54:45,840 MONTHS FROM DIAGNOSIS AND 6454 04:54:45,840 --> 04:54:49,560 CURRENT STANDARD OF CARE IS 6455 04:54:49,560 --> 04:54:51,360 INTENSIVE CHEMOTHERAPY AND LOTS 6456 04:54:51,360 --> 04:54:53,800 OF [INDISCERNIBLE] FOLLOWED BY 6457 04:54:53,800 --> 04:54:58,240 RADIATION TO YOUNG BRAIN THIS IS 6458 04:54:58,240 --> 04:55:02,080 NOT REALLY GOOD. 6459 04:55:02,080 --> 04:55:03,840 DEINTENSIFY CHEMOTHERAPY AND ADD 6460 04:55:03,840 --> 04:55:05,360 [INDISCERNIBLE] THAT IS NOT 6461 04:55:05,360 --> 04:55:08,160 SUCCESSFUL AND 2 YEAR DFS IS 6462 04:55:08,160 --> 04:55:13,960 ONLY 34% OWE ON THIS TRIAL. 6463 04:55:13,960 --> 04:55:16,200 EFFECTIVE FOR CNS RELAPSE AND 6464 04:55:16,200 --> 04:55:19,640 SEVERAL TRIALS I WILL QUICKLY 6465 04:55:19,640 --> 04:55:23,760 RUN THROUGH AND THIS IS THE 6466 04:55:23,760 --> 04:55:26,040 FIRST CHOC STUDY WHERE THEY 6467 04:55:26,040 --> 04:55:29,400 ADOPTED 5 TRIALS AND CNS 6468 04:55:29,400 --> 04:55:31,520 POSITIVITY WITHIN FIRST YEAR. 6469 04:55:31,520 --> 04:55:33,760 ON THESE TRIALS CNS YOU WANT TO 6470 04:55:33,760 --> 04:55:36,120 BE LEGIBLE AND SAW TOXICITY WAS 6471 04:55:36,120 --> 04:55:37,800 SAME AND RESPONSE WAS SAME AS 6472 04:55:37,800 --> 04:55:40,280 BONE MARROW RELAPSE AND STUDY 6473 04:55:40,280 --> 04:55:43,360 FROM CHINA LOOKED AT CNS 6474 04:55:43,360 --> 04:55:45,600 POSITIVITY AT SCREENING AND 30 6475 04:55:45,600 --> 04:55:48,000 DAYS GETTING INFUSION AND 60% OF 6476 04:55:48,000 --> 04:55:50,400 PATIENTS HAD CNS DISEASE AT TIME 6477 04:55:50,400 --> 04:55:52,080 OF INFUSION AND THEY HAVE 6478 04:55:52,080 --> 04:55:53,760 NUMBERS THAT WERE ABLE TO TELL 6479 04:55:53,760 --> 04:55:56,040 IF YOU HAD A HIGHER DISEASE 6480 04:55:56,040 --> 04:55:58,880 BURDEN IN CNS, RESPONSE WAS 6481 04:55:58,880 --> 04:56:01,560 WORSE WHETHER CNS IS 1, 2, OR 3 6482 04:56:01,560 --> 04:56:05,360 AND SHOWED INCREASED TOXICITY 6483 04:56:05,360 --> 04:56:07,720 WITH INCREASED ICANS AND DATA 6484 04:56:07,720 --> 04:56:09,920 FROM REAL-WORLD CONSORTIUM WITH 6485 04:56:09,920 --> 04:56:13,040 12 MONTH EFS IS SAME IF YOU HAVE 6486 04:56:13,040 --> 04:56:15,200 CNS DISEASE VERSUS NOT IS ABOUT 6487 04:56:15,200 --> 04:56:17,200 60% AND LAST STUDY TO SHOW HERE 6488 04:56:17,200 --> 04:56:19,800 IS THE STUDY FROM EUROPE WHERE, 6489 04:56:19,800 --> 04:56:23,320 AGAIN, 12 MONTH EFS IS ABOUT 60% 6490 04:56:23,320 --> 04:56:25,000 AND THEY SHOWED THERE WAS A 6491 04:56:25,000 --> 04:56:26,800 DROPOFF AFTER 1 YEAR IF YOU 6492 04:56:26,800 --> 04:56:30,120 DIDN'T RECEIVE ANY SUBSEQUENT 6493 04:56:30,120 --> 04:56:30,400 THERAPY. 6494 04:56:30,400 --> 04:56:34,560 HOW DO WE DRIVE CARS FORWARD 6495 04:56:34,560 --> 04:56:36,360 AFTER FIRST APPROVAL PUSHING AND 6496 04:56:36,360 --> 04:56:39,360 PUSHING NOT ABLE TO GET INDUSTRY 6497 04:56:39,360 --> 04:56:41,120 TO SUPPORT US AND MADE SLIDE A 6498 04:56:41,120 --> 04:56:43,480 FEW YEARS AGO OR COUPLE YEARS 6499 04:56:43,480 --> 04:56:45,760 AGO AND KEPT UPDATING IT AND 6500 04:56:45,760 --> 04:56:47,400 WANTED TO BRING IT FORTH HERE. 6501 04:56:47,400 --> 04:56:50,000 WE HAVE SEVERAL ACADEMIC TRIALS 6502 04:56:50,000 --> 04:56:52,200 SHOWING SUCH GREAT RESULTS HOW 6503 04:56:52,200 --> 04:56:53,760 EFFECTIVE IT COULD BE AND HOW WE 6504 04:56:53,760 --> 04:56:57,600 GET THIS TO OTHER PATIENTS NEED 6505 04:56:57,600 --> 04:56:59,920 A COUNTRY WILD WORLDWIDE AND 6506 04:56:59,920 --> 04:57:01,000 INDICATIONS FOR SECOND RELAPSE 6507 04:57:01,000 --> 04:57:02,840 WE WON'T HAVE THIS STUDY AND 6508 04:57:02,840 --> 04:57:04,520 THERAPIES THAT ARE AVAILABLE. 6509 04:57:04,520 --> 04:57:08,280 WE HAVE BEEN TRYING THROUGH 6510 04:57:08,280 --> 04:57:09,080 CHILDREN'S ONCOLOGY GROUP 6511 04:57:09,080 --> 04:57:11,800 GETTING RELAPSE STUDY OPEN 6512 04:57:11,800 --> 04:57:12,840 COUNTRYWIDE FOR FIRST RELAPSE 6513 04:57:12,840 --> 04:57:15,480 AND ARE EFFORTS AND ON TOP 6514 04:57:15,480 --> 04:57:18,400 APPROVED ONGOING STUDIES AND 6515 04:57:18,400 --> 04:57:21,240 BOTTOM NONAPPROVED NONPHARMA-AND 6516 04:57:21,240 --> 04:57:26,840 27 TAEN-FD APPROVED T-CELL. 6517 04:57:26,840 --> 04:57:30,000 SINCE BEFORE 207 TAENTO ALMOST 6518 04:57:30,000 --> 04:57:31,440 2022 SHANNON CAN VOUCH FOR THAT 6519 04:57:31,440 --> 04:57:34,760 AND HOW MANY CONVERSATIONS WITH 6520 04:57:34,760 --> 04:57:37,600 NEF AR TIS AND RELAPSE AND DOWN 6521 04:57:37,600 --> 04:57:39,360 STREAM INFANT STUDY AND EVERY 6522 04:57:39,360 --> 04:57:41,480 ONE WAS DENIED AND FINALLY THEY 6523 04:57:41,480 --> 04:57:43,480 SAID WE WILL SUPPORT STUDY BUT 6524 04:57:43,480 --> 04:57:45,360 PAY FOR IT AT MARKET RATE FOR 6525 04:57:45,360 --> 04:57:48,160 THE PRODUCT WHICH IS NOT 6526 04:57:48,160 --> 04:57:51,200 FEASIBLE. WE HAD HUMANIZED CAR 6527 04:57:51,200 --> 04:57:53,600 T DATA THAT SHANNON PUBLISHED 6528 04:57:53,600 --> 04:57:57,000 THAT WAS BEAUTIFUL AND NEVARTIS 6529 04:57:57,000 --> 04:57:58,800 BOUGHT THE RIGHTS TO IT DON'T 6530 04:57:58,800 --> 04:58:01,200 WANT TO DEVELOP IT AND SITTING 6531 04:58:01,200 --> 04:58:03,600 ON SHELF NOT DOG ANYTHING WE 6532 04:58:03,600 --> 04:58:07,160 TALKED TO KITE AND GILLI AD AND 6533 04:58:07,160 --> 04:58:08,400 TRIAL IS ONPAUSE CURRENTLY AND 6534 04:58:08,400 --> 04:58:10,640 WE WORKED WITH THEM TWO YEARS TO 6535 04:58:10,640 --> 04:58:12,680 GET A FIRST RELAPSE STUDY 6536 04:58:12,680 --> 04:58:15,480 THROUGH CRG AND MULTIPLE 6537 04:58:15,480 --> 04:58:17,280 CONCEPTS AND FINALLY THEY DENIED 6538 04:58:17,280 --> 04:58:19,520 THAT AND WE WERE A LITTLE FED UP 6539 04:58:19,520 --> 04:58:21,920 AT THIS POINT AND LET'S DO 6540 04:58:21,920 --> 04:58:25,240 ACADEMIC AND HAVE IT COGWIDE AND 6541 04:58:25,240 --> 04:58:28,360 APPLIED TO NC NEXT PROGRAM AND 6542 04:58:28,360 --> 04:58:30,440 HAD CONCEPTS FOR COG AND THIS 6543 04:58:30,440 --> 04:58:32,880 WAS DEVELOPED BY JIM AT NCI AND 6544 04:58:32,880 --> 04:58:36,760 SAW DATA THAT IS HUMANIZED HIGH 6545 04:58:36,760 --> 04:58:37,600 PERSISTENCE [INDISCERNIBLE] 6546 04:58:37,600 --> 04:58:39,240 TOXICITY AND NEXT PROGRAM LIKED 6547 04:58:39,240 --> 04:58:41,480 THE CONCEPT AND DENIED IT AND 6548 04:58:41,480 --> 04:58:43,440 THEY WERE LIKE YOU SHOW EFFICACY 6549 04:58:43,440 --> 04:58:45,280 IN FIRST RELAPSE AND THEN WHAT? 6550 04:58:45,280 --> 04:58:49,360 WON'T GO OUT TO KIDS IN THE 6551 04:58:49,360 --> 04:58:50,680 COUNTRY THAT NEED IT AND WE 6552 04:58:50,680 --> 04:58:52,120 WON'T LOOK AT YOUR APPLICATION 6553 04:58:52,120 --> 04:58:53,840 AND STARTED TO TALK TO BNS. 6554 04:58:53,840 --> 04:58:55,480 THIS IS GOING SOMEWHERE. 6555 04:58:55,480 --> 04:58:57,040 FINALLY AFTER A YEAR OF TALKING 6556 04:58:57,040 --> 04:58:59,600 TO BMS, THEY HAVE GOTTEN 6557 04:58:59,600 --> 04:59:02,360 APPROVAL FROM HIGHER UPS AND 6558 04:59:02,360 --> 04:59:04,760 FUNDING TO AMEND ONGOING STUDY 6559 04:59:04,760 --> 04:59:07,800 AND INCLUDE PATIENTS WITH FIRST 6560 04:59:07,800 --> 04:59:11,600 RELAPSE AS A COG COHORT WHERE WE 6561 04:59:11,600 --> 04:59:14,280 HAVE STATISTICS SHOWING CD19 IS 6562 04:59:14,280 --> 04:59:16,400 BETTER STANDARD OF CARE FOR 6563 04:59:16,400 --> 04:59:18,040 FIRST RELAPSE AND TRIAL WAS 6564 04:59:18,040 --> 04:59:20,040 DECISION MADE A COUPLE WEEKS AGO 6565 04:59:20,040 --> 04:59:23,000 AND SEE IF IT GOES FORWARD WITH 6566 04:59:23,000 --> 04:59:26,520 FINGERS CROSSED AND WE HEARD 6567 04:59:26,520 --> 04:59:28,400 CLAUDIA DURING LUNCH TIME WON'T 6568 04:59:28,400 --> 04:59:31,080 BE DECENTRALIZED APPROACH LIKE 6569 04:59:31,080 --> 04:59:34,600 DOING IN EUROPE USING NCI NEXT 6570 04:59:34,600 --> 04:59:36,560 PLATFORM IN DERISKING IT FOR 6571 04:59:36,560 --> 04:59:37,920 COMPANY AND WE MIGHT BE ABLE TO 6572 04:59:37,920 --> 04:59:41,120 GO AHEAD ON THAT TOO. 6573 04:59:41,120 --> 04:59:42,400 CHALLENGES AND NEXT STEPS I 6574 04:59:42,400 --> 04:59:44,880 DON'T KNOW HOW TO PUT THAT IN A 6575 04:59:44,880 --> 04:59:46,440 SLIDE OR 2 BUT WE TALK THE ABOUT 6576 04:59:46,440 --> 04:59:48,320 IT AND WON'T GO ABOUT IT IN EACH 6577 04:59:48,320 --> 04:59:50,240 DETAIL BUT WE HAVE TO 6578 04:59:50,240 --> 04:59:51,320 INCORPORATE EARLIER IN THE 6579 04:59:51,320 --> 04:59:52,840 COURSE OF DISEASE AND TALKED 6580 04:59:52,840 --> 04:59:55,760 ABOUT RESISTANCE AND HOW TO 6581 04:59:55,760 --> 04:59:58,080 OVERCOME THAT AND CAR T-CELL 6582 04:59:58,080 --> 04:59:59,760 LOSS AND T-CELL EXHAUSTION AND 6583 04:59:59,760 --> 05:00:01,400 HEARD ABOUT NEW CONSTRUCTS AND 6584 05:00:01,400 --> 05:00:02,920 AMAZING RESULTS WE ARE GETTING 6585 05:00:02,920 --> 05:00:05,960 AND HOW DO WE MONTH OF THIS 6586 05:00:05,960 --> 05:00:07,360 FORWARD? UNIQUE SEVERE 6587 05:00:07,360 --> 05:00:08,800 TOXICITIES WE TALKED ABOUT TOO 6588 05:00:08,800 --> 05:00:11,400 AND HAVE TO MAKE THERAPIES MORE 6589 05:00:11,400 --> 05:00:13,080 TOLERABLE. DEVELOPING 6590 05:00:13,080 --> 05:00:14,400 AFFORDABLE AND ACCESSIBLE 6591 05:00:14,400 --> 05:00:16,200 DELIVERY METHODS WE TALKED ABOUT 6592 05:00:16,200 --> 05:00:17,560 IT TOO WHETHER WE HAVE 6593 05:00:17,560 --> 05:00:19,640 COLLABORATIVE MODELS WITH 6594 05:00:19,640 --> 05:00:22,360 PHARMAOR POINT OF CARRACKDEMIC 6595 05:00:22,360 --> 05:00:25,480 MANUFACTURER AND CLAUDIA SAID WE 6596 05:00:25,480 --> 05:00:28,200 HAVE TO ALL WORK TOGETHER HOW DO 6597 05:00:28,200 --> 05:00:30,480 WE GET TO REST OF THE WORLD AND 6598 05:00:30,480 --> 05:00:32,360 LOOK AT COST AND LOW AND MIDDLE 6599 05:00:32,360 --> 05:00:34,720 INCOME COUNTRIES AND WHO CAN 6600 05:00:34,720 --> 05:00:36,760 AFFORD THIS? WE HAVE TO THINK 6601 05:00:36,760 --> 05:00:40,800 ABOUT THAT TOO. I WANT TO THANK 6602 05:00:40,800 --> 05:00:43,560 EVERYBODY LEADERSHIP AND NIRALI 6603 05:00:43,560 --> 05:00:47,200 AND MICHAEL HELPED ME PUSH THIS 6604 05:00:47,200 --> 05:00:50,800 AS A COG NEXT STUDY AND SAT IN 6605 05:00:50,800 --> 05:00:52,640 MEETINGS WITH EVERY PHARMA 6606 05:00:52,640 --> 05:00:55,000 TRYING TO EXPLAIN HOW NCI COULD 6607 05:00:55,000 --> 05:00:57,200 SUPPORT THEM AND WE SO FAR HAVE 6608 05:00:57,200 --> 05:00:59,320 A FEW BITES. I WILL SEE HOW 6609 05:00:59,320 --> 05:01:02,480 THAT GOES. THANK YOU. 6610 05:01:02,480 --> 05:01:10,640 >> NEXT HEARING FROM DR. KAREN 6611 05:01:10,640 --> 05:01:12,560 CHAO ABOUT ACCESS TO CAR 6612 05:01:12,560 --> 05:01:12,840 T-CELLS. 6613 05:01:12,840 --> 05:01:15,160 >> I WILL TALK ABOUT BARRIERS TO 6614 05:01:15,160 --> 05:01:17,040 ACCESSING CAR T THERAPY AND 6615 05:01:17,040 --> 05:01:19,600 POTENTIAL SOLUTIONS FOR PATIENTS 6616 05:01:19,600 --> 05:01:21,600 MOVING FORWARD AND STARTING IT 6617 05:01:21,600 --> 05:01:23,560 SUMMARIZES BARRIERS TO ACCESSING 6618 05:01:23,560 --> 05:01:26,960 CAR T THERAPY FROM STAKEHOLDER 6619 05:01:26,960 --> 05:01:29,360 PERSPECTIVES AND FROM PATIENT 6620 05:01:29,360 --> 05:01:30,720 PROVIDER MANUFACTURER 6621 05:01:30,720 --> 05:01:33,840 PERSPECTIVES AND ADDING A 4TH 6622 05:01:33,840 --> 05:01:34,800 PERSPECTIVE FROM RESEARCH 6623 05:01:34,800 --> 05:01:36,680 ENTERPRISE AND BARRIERS ARE 6624 05:01:36,680 --> 05:01:38,760 FAMILIAR NOT EXCLUSIVE TO CAR T 6625 05:01:38,760 --> 05:01:41,160 THERAPY ALONE AND ON UPCOMING 6626 05:01:41,160 --> 05:01:43,080 SLIDES I WILL GO INTO EACH 6627 05:01:43,080 --> 05:01:45,960 PERSPECTIVE IN DEPTH. PATIENT 6628 05:01:45,960 --> 05:01:47,880 PERSPECTIVE LARGE HURDLE 6629 05:01:47,880 --> 05:01:49,000 ACCESSING CAR T THERAPY IS 6630 05:01:49,000 --> 05:01:52,200 PHYSICAL ACCESS TO INSTITUTION 6631 05:01:52,200 --> 05:01:53,320 ADMINISTERING CAR T THERAPY AND 6632 05:01:53,320 --> 05:01:56,160 THEY ARE AVAILABLE AT FACT 6633 05:01:56,160 --> 05:01:59,040 CERTIFIED CENTERS AND SCENARIO 6634 05:01:59,040 --> 05:02:02,760 OR DEMAND GREATLY OUTSTRIPS 6635 05:02:02,760 --> 05:02:05,880 SUPPLY AND CERTIFIED CENTERS IN 6636 05:02:05,880 --> 05:02:10,320 US FOR PEDIATRIC HEM ATTOPOETIC 6637 05:02:10,320 --> 05:02:14,160 STEM CELL PLANT AND PROXIES 6638 05:02:14,160 --> 05:02:15,680 ADMINISTERING FOR PATIENTS AND 6639 05:02:15,680 --> 05:02:18,320 OFTEN ARE SYNONYMOUS AND THESE 6640 05:02:18,320 --> 05:02:21,200 FACT ACCREDITED CENTERS ARE MORE 6641 05:02:21,200 --> 05:02:24,640 POPULATION DENSE AREAS AND OUTER 6642 05:02:24,640 --> 05:02:27,200 EDGES OF THESE SERVICE LOOKING 6643 05:02:27,200 --> 05:02:29,040 AREAS ARE TRAVELING UP TO 3 6644 05:02:29,040 --> 05:02:32,040 HOURS AND CENTERS IN SOUTHWEST 6645 05:02:32,040 --> 05:02:35,360 AND MIDWEST AND PLAIN STATES ARE 6646 05:02:35,360 --> 05:02:37,960 SPARSELY RESUSCITATED AND TRAVEL 6647 05:02:37,960 --> 05:02:39,680 AND TRAVELING LONG DISTANCE IN 6648 05:02:39,680 --> 05:02:41,960 STATES AND PATIENTS TRAVELING IN 6649 05:02:41,960 --> 05:02:44,600 MORE RURAL AREAS AND HIDDEN 6650 05:02:44,600 --> 05:02:48,560 COSTS OF RECEIVING CAR T THERAPY 6651 05:02:48,560 --> 05:02:52,560 AND TRAVEL AND LODGING EXPENSES. 6652 05:02:52,560 --> 05:02:55,680 COSTS MEALS HOTEL STAYS 6653 05:02:55,680 --> 05:02:57,000 INCREASING DECREASE INCOME OR 6654 05:02:57,000 --> 05:03:01,280 LOSS OF INCOME FOR ONE OR BOTH 6655 05:03:01,280 --> 05:03:04,960 CAREGIVERS REQUIRING RISK 6656 05:03:04,960 --> 05:03:07,040 MITIGATION AND PATIENTS AND 6657 05:03:07,040 --> 05:03:08,600 FAMILIES HAVE TO BUDGET FOR MORE 6658 05:03:08,600 --> 05:03:11,480 TIME TO BE WITHIN MANDATED 30 6659 05:03:11,480 --> 05:03:13,400 MINUTES TO TWO HOUR DRIVING 6660 05:03:13,400 --> 05:03:16,840 SYSTEMS IN REFERRAL INSTITUTION 6661 05:03:16,840 --> 05:03:18,120 FOR ADEQUATE SAFETY MONITORING 6662 05:03:18,120 --> 05:03:22,280 AND TREATMENT FOR RELATED 6663 05:03:22,280 --> 05:03:22,920 TOXICITIES. 6664 05:03:22,920 --> 05:03:24,920 UTILIZATION MANAGEMENT POLICIES 6665 05:03:24,920 --> 05:03:26,560 ARE IMPOSED BY INSURANCE 6666 05:03:26,560 --> 05:03:28,560 COMPANIES AND POLICIES INCLUDE 6667 05:03:28,560 --> 05:03:30,640 NEED TO GET PRIOR AUTHORIZATIONS 6668 05:03:30,640 --> 05:03:32,800 OR STEPWISE THERAPY WHERE 6669 05:03:32,800 --> 05:03:33,880 PATIENTS HAVE DEMONSTRATED 6670 05:03:33,880 --> 05:03:36,200 FAILURE OF MULTIPLE LINES OF 6671 05:03:36,200 --> 05:03:37,000 THERAPY PRIOR TO AUTHORIZATION 6672 05:03:37,000 --> 05:03:39,840 FOR CAR AND STEPS DELAY ACCESS 6673 05:03:39,840 --> 05:03:42,240 TO IN-PATIENTS WHOSE NEED FOR 6674 05:03:42,240 --> 05:03:44,880 CAR IS TIME SENSITIVE AND 6675 05:03:44,880 --> 05:03:46,360 MEDICAL BILL STANDPOINT COPAYS 6676 05:03:46,360 --> 05:03:48,560 ARE HIGHER GIVEN HIGHER COSTS OF 6677 05:03:48,560 --> 05:03:52,040 CAR AND POTENTIAL COSTS OF 6678 05:03:52,040 --> 05:03:53,800 TOXICITY MANAGEMENT AND THERE IS 6679 05:03:53,800 --> 05:03:56,600 POTENTIAL TO REFER TO DEFERRAL 6680 05:03:56,600 --> 05:03:58,760 -- PREVIOUS COMORBIDITIES AS A 6681 05:03:58,760 --> 05:04:00,960 RESULT OF TREATMENT RELATED 6682 05:04:00,960 --> 05:04:04,400 COMPLICATIONS FOR FEAR OF 6683 05:04:04,400 --> 05:04:07,560 RELATED CAR TOXICITIES MEDICAL 6684 05:04:07,560 --> 05:04:10,600 PROVIDER AND STANDPOINT 6685 05:04:10,600 --> 05:04:12,240 GEOGRAPHY PLAY AZ ROLE HERE 6686 05:04:12,240 --> 05:04:15,120 MONITORING PATIENTS LOCALLY THAN 6687 05:04:15,120 --> 05:04:19,440 REFERRING TO INSTITUTION THAT IS 6688 05:04:19,440 --> 05:04:19,760 FURTHER. 6689 05:04:19,760 --> 05:04:21,920 PREVENS FOR CLOSER TREATMENT IS 6690 05:04:21,920 --> 05:04:24,160 DIFFICULT TO ACHIEVE TO 6691 05:04:24,160 --> 05:04:26,120 DISTANCED FACT CERTIFIED CENTER 6692 05:04:26,120 --> 05:04:27,760 LOGISTICAL DIFFICULTIES 6693 05:04:27,760 --> 05:04:28,760 COORDINATING FOLLOW UP FOR 6694 05:04:28,760 --> 05:04:31,280 PATIENTS INCLUDING MAINTAINING 6695 05:04:31,280 --> 05:04:33,240 EFFECTIVE COMMUNICATION BETWEEN 6696 05:04:33,240 --> 05:04:35,360 PRIMARY ONKOLS AND REFERRAL 6697 05:04:35,360 --> 05:04:38,120 INSTITUTION AND HOSPITALS THERE 6698 05:04:38,120 --> 05:04:39,640 IS CONSIDERATION OF 6699 05:04:39,640 --> 05:04:40,840 REIMBURSEMENT STRUCTURE OF CAR T 6700 05:04:40,840 --> 05:04:43,120 THERAPY AND ITERATIVE CHANGES 6701 05:04:43,120 --> 05:04:44,880 THAT HAVE HAPPENED OVER TIME AND 6702 05:04:44,880 --> 05:04:48,160 CURRENT REIMBURSEMENT DOESN'T 6703 05:04:48,160 --> 05:04:50,040 OFTEN SUFFICIENTLY COVER COSTS 6704 05:04:50,040 --> 05:04:52,840 OF CAR OR TREATMENT SERVICES AND 6705 05:04:52,840 --> 05:04:55,080 DOESN'T DISINCENTIVIZE HOSPITALS 6706 05:04:55,080 --> 05:04:58,440 TO PROVIDE CAR T THERAPY TO 6707 05:04:58,440 --> 05:04:59,440 PATIENTS ADMINISTRATION OF 6708 05:04:59,440 --> 05:05:01,600 THERAPY REQUIRES INSTITUTION 6709 05:05:01,600 --> 05:05:02,920 STAFFING HIGHLY SPECIALIZED 6710 05:05:02,920 --> 05:05:05,800 TEAMS PHYSICIANS AND APPS AND 6711 05:05:05,800 --> 05:05:07,960 NURSES AND CLINICAL SUPPORT 6712 05:05:07,960 --> 05:05:09,480 STAFF AND INTAKE SPECIALISTS AND 6713 05:05:09,480 --> 05:05:13,000 SOCIAL WORKERS AND CASE MANAGERS 6714 05:05:13,000 --> 05:05:16,000 AND FINANCIAL SUPPORT STAFF 6715 05:05:16,000 --> 05:05:20,400 HELPING WITH NEGOTIATIONS AND 6716 05:05:20,400 --> 05:05:24,680 [INDISCERNIBLE] -- 6717 05:05:24,680 --> 05:05:26,560 REGRESSES FROM REFERRAL TO CAR 6718 05:05:26,560 --> 05:05:30,720 TO AFORESIS TO MANUFACTURING AND 6719 05:05:30,720 --> 05:05:32,520 LIMITED PRODUCTION SLOTS 6720 05:05:32,520 --> 05:05:36,360 MANUFACTURERS CREATING RATE 6721 05:05:36,360 --> 05:05:40,200 LIMITING STEP -- FROM AFORESIS 6722 05:05:40,200 --> 05:05:43,440 TO INFUSION THERE IS 3 TO 5 WEEK 6723 05:05:43,440 --> 05:05:45,600 TURNAROUND FOR MANUFACTURING AND 6724 05:05:45,600 --> 05:05:48,000 QUALITY ASSESSMENT CHECKS AND 6725 05:05:48,000 --> 05:05:50,320 SPECIFIC NATURE MANUFACTURING 6726 05:05:50,320 --> 05:05:54,280 CAR LEADS TO DIFFICULTY IN 6727 05:05:54,280 --> 05:05:55,880 SCALING SCALABILITY OF 6728 05:05:55,880 --> 05:05:57,400 MANUFACTURING PRODUCTS AND 6729 05:05:57,400 --> 05:05:59,800 BITECH COMPANIES SEE CHALLENGES 6730 05:05:59,800 --> 05:06:02,720 CAR MANUFACTURERS ARE UNDERGOING 6731 05:06:02,720 --> 05:06:04,400 INNOVATIVE THERAPIES IN PIPELINE 6732 05:06:04,400 --> 05:06:06,000 MAY BE EFFECTED COMPANIES 6733 05:06:06,000 --> 05:06:09,160 SHIFTING PRIORITIES TO EASIER 6734 05:06:09,160 --> 05:06:11,200 PATH TO COMMERCIAL VIABILITY AND 6735 05:06:11,200 --> 05:06:12,760 PERSPECTIVE OF RESEARCH 6736 05:06:12,760 --> 05:06:14,520 ENTERPRISE OUTSTANDING CLINICAL 6737 05:06:14,520 --> 05:06:15,920 QUESTIONS WE HAVE GONE OVER 6738 05:06:15,920 --> 05:06:17,360 TODAY AND MIGHT NOT BE OPEN 6739 05:06:17,360 --> 05:06:19,000 CLINICAL TRIALS SUCH AS ONES 6740 05:06:19,000 --> 05:06:21,600 LOOKING AT HUMANIZED FAST CAR OR 6741 05:06:21,600 --> 05:06:23,640 EARLY B CELL RECOVERY CAR 6742 05:06:23,640 --> 05:06:26,480 INFANTS AND CNS RELAPSE AND 6743 05:06:26,480 --> 05:06:27,360 AVAILABLE CLINICAL TRIALS MIGHT 6744 05:06:27,360 --> 05:06:29,480 NOT BE OPEN AND AVAILABLE FOR 6745 05:06:29,480 --> 05:06:31,600 PATIENTS WHEN THEY NEED THEM AND 6746 05:06:31,600 --> 05:06:34,880 PER CLINICAL TRIALS ELIGIBILITY 6747 05:06:34,880 --> 05:06:37,480 IS OFTEN STRICT AND LIMITED 6748 05:06:37,480 --> 05:06:40,240 RESOURCES TO RECRUIT PATIENTS 6749 05:06:40,240 --> 05:06:42,440 AND DESPITE CONCERTED AND 6750 05:06:42,440 --> 05:06:44,680 MANDATED EFFORT BY NIH TO 6751 05:06:44,680 --> 05:06:48,320 INCLUDE WOMEN AND PATIENTS IN 6752 05:06:48,320 --> 05:06:50,360 CLINICAL TRIALS SINCE 90S TO 6753 05:06:50,360 --> 05:06:52,440 DATE AND RECRUITING 6754 05:06:52,440 --> 05:06:55,160 REPRESENTATIVE MINORITY 6755 05:06:55,160 --> 05:06:58,320 PARTICIPANTS AND PIE GRAPH HAS 6756 05:06:58,320 --> 05:07:00,280 RACIAL AND ETHNIC BREAKDOWN IN 6757 05:07:00,280 --> 05:07:02,320 CLINICAL TRIALS IS SIMILAR IN 6758 05:07:02,320 --> 05:07:04,240 CANCER CLINICAL TRIALS INCLUDING 6759 05:07:04,240 --> 05:07:06,480 ONCE FOR PEDIATRIC PATIENTS AND 6760 05:07:06,480 --> 05:07:08,880 SOME POTENTIAL SOLUTIONS TO 6761 05:07:08,880 --> 05:07:10,360 IMPROVING ACCESS AS I HAVE 6762 05:07:10,360 --> 05:07:12,680 BROKEN THEM DOWN TO THREE MAJOR 6763 05:07:12,680 --> 05:07:15,480 AREAS AND FROM A FINANCIAL 6764 05:07:15,480 --> 05:07:16,440 STANDPOINT ADDRESSING FINANCIAL 6765 05:07:16,440 --> 05:07:18,960 TOXICITY OF PROCESS OF CAR 6766 05:07:18,960 --> 05:07:20,880 ADMINISTRATION IS IMPORTANT FOR 6767 05:07:20,880 --> 05:07:22,720 PATIENT AND FAMILY AND PATIENT 6768 05:07:22,720 --> 05:07:24,800 ASSISTANCE PROGRAMS MANY DON'T 6769 05:07:24,800 --> 05:07:27,000 INCLUDE INCIDENTAL COSTS RELATED 6770 05:07:27,000 --> 05:07:29,280 TO TRAVEL AND EXPANSION OF 6771 05:07:29,280 --> 05:07:30,680 PROGRAMS TO INCLUDE HIDDEN COSTS 6772 05:07:30,680 --> 05:07:33,080 OF GETTING CAR HELPED REMOVE 6773 05:07:33,080 --> 05:07:35,960 FINANCIAL DIFFICULTIES THAT SOME 6774 05:07:35,960 --> 05:07:38,040 PATIENTS MIGHT BASE AND CHIMERA 6775 05:07:38,040 --> 05:07:40,440 TRAVEL ASSISTANCE PROGRAM AIMS 6776 05:07:40,440 --> 05:07:42,880 TO LOW INCOME PATIENTS ELIGIBLE 6777 05:07:42,880 --> 05:07:45,560 WITH EXPENSES INCURRED DURING 6778 05:07:45,560 --> 05:07:47,480 TRAVEL FOR CAR ADMINISTRATION 6779 05:07:47,480 --> 05:07:49,840 AND POST CAR MONITORING PERIOD 6780 05:07:49,840 --> 05:07:51,400 AND IS A FEW CENTERS IN UNITED 6781 05:07:51,400 --> 05:07:53,200 STATES THAT WORKS WITH PATIENTS 6782 05:07:53,200 --> 05:07:56,560 TO OFFER FREE OR SUBSIDIZED 6783 05:07:56,560 --> 05:07:58,520 HOUSING TO RECEIVE CAR T 6784 05:07:58,520 --> 05:07:59,680 TREATMENT AND FINANCIAL 6785 05:07:59,680 --> 05:08:02,800 COUNSELING SERVICES FOR PATIENT 6786 05:08:02,800 --> 05:08:04,040 INFORMING THEM ABOUT DIRECT AND 6787 05:08:04,040 --> 05:08:07,040 INDIRECT COSTS OF SEEKING CAR T 6788 05:08:07,040 --> 05:08:09,880 THERAPY AND HELPING THEM 6789 05:08:09,880 --> 05:08:12,320 NAVIGATE THROUGH VARIOUS 6790 05:08:12,320 --> 05:08:13,280 ASSISTANCE OPTIONS AVAILABLE TO 6791 05:08:13,280 --> 05:08:15,400 THEM AND PROGRAMS MAY HELP 6792 05:08:15,400 --> 05:08:17,480 REMOVE RELIANCE ON MANUFACTURING 6793 05:08:17,480 --> 05:08:19,920 AND CHARITABLE ORGANIZATIONS OR 6794 05:08:19,920 --> 05:08:21,800 CROWDFUNDING FROM FAMILIES AND 6795 05:08:21,800 --> 05:08:24,840 FRIENDS THAT IS PATCHWORK AND 6796 05:08:24,840 --> 05:08:26,960 LARGELY UNRELIABLE SAFETY NET 6797 05:08:26,960 --> 05:08:29,960 FROM PATIENTS GEOGRAPHICAL 6798 05:08:29,960 --> 05:08:31,800 STANDPOINT AND SETTINGS WITH 6799 05:08:31,800 --> 05:08:34,200 CARS INCREASE ACCESS TO MANY 6800 05:08:34,200 --> 05:08:37,600 TREATMENT CENTERS MOVING TOWARDS 6801 05:08:37,600 --> 05:08:39,440 OUTPATIENT CAR INFUSION AND 6802 05:08:39,440 --> 05:08:41,520 EXPANDING CENTERS TO COMMUNITY 6803 05:08:41,520 --> 05:08:43,680 TRANSPLANT CENTERS THAT ARE NOT 6804 05:08:43,680 --> 05:08:45,680 FACT CERTIFIED MIGHT BE ONE 6805 05:08:45,680 --> 05:08:46,880 SHORT TERM SOLUTION TALKING 6806 05:08:46,880 --> 05:08:48,800 ABOUT TODAY AS WELL 6807 05:08:48,800 --> 05:08:49,880 DECENTRALIZING CAR MANUFACTURING 6808 05:08:49,880 --> 05:08:53,520 TO BE DEVELOPED LOCALLY WOULD 6809 05:08:53,520 --> 05:08:55,080 IMPROVE EFFICIENCY AND ACCESS TO 6810 05:08:55,080 --> 05:08:58,120 HELP DECREASE OVERALL COSTS AND 6811 05:08:58,120 --> 05:09:02,560 FROM BIOMEDICAL STANDPOINT 6812 05:09:02,560 --> 05:09:04,320 AUTOMATION WOULD HELP BOOST THIS 6813 05:09:04,320 --> 05:09:06,680 PROCESS AND MENTIONED MANY TIMES 6814 05:09:06,680 --> 05:09:09,600 TODAY AND IN OFF THE SHELF 6815 05:09:09,600 --> 05:09:11,600 THERAPIES DON'T REQUIRE FORESIS 6816 05:09:11,600 --> 05:09:13,440 WHO HELP SHORTEN MANUFACTURING 6817 05:09:13,440 --> 05:09:16,920 TIME AND PEDIATRIC WORLDWIDE 6818 05:09:16,920 --> 05:09:18,680 CONSORTIUM TWO EFFORTS AIM AT 6819 05:09:18,680 --> 05:09:20,880 BETTER UNDERSTANDING PATIENT 6820 05:09:20,880 --> 05:09:23,200 EXPERIENCE AND PATIENT PERCEIVED 6821 05:09:23,200 --> 05:09:26,800 BARRIERS TO CARE AND REAL WORLD 6822 05:09:26,800 --> 05:09:32,560 COST TO ADMINISTERING CAR IS. 6823 05:09:32,560 --> 05:09:35,280 THERE WILL BE THREE VERSIONS AND 6824 05:09:35,280 --> 05:09:38,000 PATIENT SELF REPORT FOR PATIENTS 6825 05:09:38,000 --> 05:09:41,040 OVER 18 PARENT CAREGIVER PROXY 6826 05:09:41,040 --> 05:09:43,600 FOR THOSE LESS THAN 18 YEARS OF 6827 05:09:43,600 --> 05:09:47,200 ANL AND NEXT OF KIN SURVEY FOR 6828 05:09:47,200 --> 05:09:50,520 PATIENTS THAT PASSED AND 6829 05:09:50,520 --> 05:09:54,240 QUESTIONS INCLUDE FOLLOW UPS AND 6830 05:09:54,240 --> 05:09:55,280 HOUSEHOLD MATERIAL HARDSHIP AND 6831 05:09:55,280 --> 05:09:57,880 AS WELL AS PERCEIVED BARRIERS TO 6832 05:09:57,880 --> 05:10:00,800 ACCESS AT CAR T INSTITUTION AND 6833 05:10:00,800 --> 05:10:02,920 WILL ALSO BE PATIENT REPORTED 6834 05:10:02,920 --> 05:10:05,600 OUTCOMES THAT WILL BE UTILIZING 6835 05:10:05,600 --> 05:10:07,600 PROMISE MEASURES ACROSS 7 6836 05:10:07,600 --> 05:10:10,160 DOMAINS AND OTHER EFFORT IS A 6837 05:10:10,160 --> 05:10:11,720 REAL WORLD FINANCIAL COST 6838 05:10:11,720 --> 05:10:14,360 ANALYSIS AND PREVIOUS WORK BY 6839 05:10:14,360 --> 05:10:17,320 LYNNE ET AL. EVALUATED COST 6840 05:10:17,320 --> 05:10:20,280 EFFECT AND THEY ARE CONTAINING 6841 05:10:20,280 --> 05:10:23,000 REGIMENTS USING FINANCIAL 6842 05:10:23,000 --> 05:10:25,000 MODELING TO CALCULATE QUALITY 6843 05:10:25,000 --> 05:10:27,520 ADJUSTED LIFE BASED ON VARIOUS 6844 05:10:27,520 --> 05:10:32,400 RATES OF EFS WITH 40% 5 YEAR EFS 6845 05:10:32,400 --> 05:10:37,600 WITH COST IS 61,000 PER EQUALI 6846 05:10:37,600 --> 05:10:40,600 AND 5 YEAR EFS DROPS THIS DROPS 6847 05:10:40,600 --> 05:10:44,440 AS WELL AND REDUCING OVERALL 6848 05:10:44,440 --> 05:10:46,640 COST OF CHIMERA TO HALF THAT 6849 05:10:46,640 --> 05:10:51,200 PRICE TAG WOULD ALLOW IT TO MEET 6850 05:10:51,200 --> 05:10:56,280 MORE ACCEPTABLE STAND AARD REAL 6851 05:10:56,280 --> 05:10:58,040 WORLD FINANCIAL COST ANALYSIS IS 6852 05:10:58,040 --> 05:10:59,600 PAIRING CLINICAL DATA COLLECTED 6853 05:10:59,600 --> 05:11:03,280 IN PRWCC AND ENCOUNTER LEVEL 6854 05:11:03,280 --> 05:11:04,400 BILLING CHARGE DATA THAT IS 6855 05:11:04,400 --> 05:11:07,120 SHARED WITH FIZZ THAT IS THE 6856 05:11:07,120 --> 05:11:08,080 PEDIATRIC HOSPITAL INFORMATION 6857 05:11:08,080 --> 05:11:12,160 SYSTEMS AND IN THE ORIGINAL 15 6858 05:11:12,160 --> 05:11:15,360 INSTITUTIONS MAKING UP PRWCC10 6859 05:11:15,360 --> 05:11:17,480 SHARE DATA WITH THIS. WE HAVE 6860 05:11:17,480 --> 05:11:20,040 BEEN ABLE TO PULL ABOUT 100 6861 05:11:20,040 --> 05:11:22,200 PATIENTS FROM DATA AND BOTH 6862 05:11:22,200 --> 05:11:23,640 DATABASES AND FINALIZING DATA 6863 05:11:23,640 --> 05:11:27,240 SET FOR ANALYSIS. 6864 05:11:27,240 --> 05:11:32,360 THANK YOU. 6865 05:11:32,360 --> 05:11:35,680 >> THANK YOU, KAREN MOVING TO 6866 05:11:35,680 --> 05:11:41,000 ANGELA TALKING ABOUT PATIENT 6867 05:11:41,000 --> 05:11:51,360 REPORTED OUTCOMES. 6868 05:11:52,120 --> 05:11:55,400 >> GOOD AFTERNOON I'M ANGIE AND 6869 05:11:55,400 --> 05:11:57,600 GRATEFUL TO TALK ABOUT PATIENT 6870 05:11:57,600 --> 05:12:00,920 REPORTED OUTCOMES VALUE OF 6871 05:12:00,920 --> 05:12:04,320 FUTURE CORRECTIONS IN CAR T-CELL 6872 05:12:04,320 --> 05:12:12,920 THERAPY. 6873 05:12:12,920 --> 05:12:14,880 THERE WE GO ALL RIGHT WE HEARD 6874 05:12:14,880 --> 05:12:17,920 OF TREMENDOUS WORK BEING DONE IN 6875 05:12:17,920 --> 05:12:21,360 CAR T-CELL THERAPY THAT IS 6876 05:12:21,360 --> 05:12:22,360 PEDIATRIC AND ALL IS EXCITING 6877 05:12:22,360 --> 05:12:23,720 AND COMMON THEME WE ARE HERE 6878 05:12:23,720 --> 05:12:27,960 TODAY IS TO FIND WAYS TO HELP 6879 05:12:27,960 --> 05:12:29,760 FIND CHILDREN WITH CANCER TO 6880 05:12:29,760 --> 05:12:32,760 LIVE HEALTHIER AND LONGER LIVES 6881 05:12:32,760 --> 05:12:35,840 AND KAPLAN MEYER CURVE WE AGREE 6882 05:12:35,840 --> 05:12:37,480 THIS PROVIDES SUPERIOR CARE TO 6883 05:12:37,480 --> 05:12:40,280 THE BLUE ARM AND WE CAN ALL 6884 05:12:40,280 --> 05:12:41,720 AGREE THE GOLD ARM SHOULD BECOME 6885 05:12:41,720 --> 05:12:44,680 THE STANDARD OF CARE AND WE KNOW 6886 05:12:44,680 --> 05:12:47,720 PATIENT REPORTED OUTCOMES 6887 05:12:47,720 --> 05:12:49,960 IMPROVE CLINICAL OUTCOMES AND 6888 05:12:49,960 --> 05:12:52,440 RCT WHERE ADULTS RECEIVED USUAL 6889 05:12:52,440 --> 05:12:56,560 CARE OR COMPLETED PATIENT 6890 05:12:56,560 --> 05:12:58,760 REPORTED OUTCOMES SYSTEM 6891 05:12:58,760 --> 05:13:00,600 ASSESSMENTS FROM STUDY WE 6892 05:13:00,600 --> 05:13:02,400 LEARNED PATIENT REPORTED 6893 05:13:02,400 --> 05:13:03,520 OUTCOMES IMPROVE QUALITY OF LIFE 6894 05:13:03,520 --> 05:13:05,560 AND SATISFACTION AND DECREASE 6895 05:13:05,560 --> 05:13:07,440 RESOURCE UTILIZATION AND 6896 05:13:07,440 --> 05:13:09,080 INCREASE SURVIVAL AND OTHER 6897 05:13:09,080 --> 05:13:11,280 STUDIES WE LEARNED THAT BASELINE 6898 05:13:11,280 --> 05:13:13,280 PATIENT REPORTED OUTCOMES ARE 6899 05:13:13,280 --> 05:13:18,160 STRONGER PREDICTOR OF SURVIVAL 6900 05:13:18,160 --> 05:13:21,600 THAN MANY OTHERS SURVIVORS IN 6901 05:13:21,600 --> 05:13:29,600 BONE MARROW TRANSPLANTS -- 6902 05:13:29,600 --> 05:13:32,200 INDEPENDENT CRITERION FOR 6903 05:13:32,200 --> 05:13:38,960 APPROVAL OF NEW DRUGS TREMENDOUS 6904 05:13:38,960 --> 05:13:39,480 VALUE 6905 05:13:39,480 --> 05:13:41,200 VALUE. WHAT IS A PATIENT 6906 05:13:41,200 --> 05:13:43,160 REPORTED OUTCOME? WE HAVE HEARD 6907 05:13:43,160 --> 05:13:45,600 A LOT ABOUT THEM TODAY PATIENT 6908 05:13:45,600 --> 05:13:48,720 REPORTED OUTCOME OR PRO IS 6909 05:13:48,720 --> 05:13:51,120 MEASURE OF ASPECT OF PATIENT 6910 05:13:51,120 --> 05:13:53,720 STATUS OR WELL BEING COMING FROM 6911 05:13:53,720 --> 05:13:55,920 PATIENT NOT FROM CAREGIVER OR 6912 05:13:55,920 --> 05:13:58,280 CLINICIAN AND OUTCOMES USE TODAY 6913 05:13:58,280 --> 05:14:00,360 MEASURE CONSTRUCTS LIKE SYMPTOMS 6914 05:14:00,360 --> 05:14:03,280 QUALITY OF LIFE AND 6915 05:14:03,280 --> 05:14:03,840 PSYCHOLOGICAL DISTRESS AND 6916 05:14:03,840 --> 05:14:05,440 FINANCIAL WELLBEING AMONG MANY 6917 05:14:05,440 --> 05:14:07,280 OTHERS AND PATIENT REPORTED 6918 05:14:07,280 --> 05:14:08,800 OUTCOMES USE VALIDATED 6919 05:14:08,800 --> 05:14:11,800 INSTRUMENTS APPLYING ARIG ROUS 6920 05:14:11,800 --> 05:14:15,560 DATA COLLECTIONS AND METHODS AND 6921 05:14:15,560 --> 05:14:17,600 ANALYSIS AND UNDERSTANDING 6922 05:14:17,600 --> 05:14:19,600 IMPORTANT DISEASE EXPERIENCE 6923 05:14:19,600 --> 05:14:23,480 WHEN DO SYSTEMS PEAK AND HOW 6924 05:14:23,480 --> 05:14:25,600 DOES TREATMENT EFFECT 6925 05:14:25,600 --> 05:14:26,360 CAREGIVERS? 6926 05:14:26,360 --> 05:14:28,520 IN CHILDREN THIS MEANS DIRECTLY 6927 05:14:28,520 --> 05:14:31,960 ASKING THE CHILD AND CHILDREN 6928 05:14:31,960 --> 05:14:32,880 PROVIDE DISTINCTIVELY IMPORTANT 6929 05:14:32,880 --> 05:14:34,160 PERSPECTIVE COMPARED TO PARENTS 6930 05:14:34,160 --> 05:14:37,200 AND MEDICAL TEAM THAT IS 6931 05:14:37,200 --> 05:14:40,000 DRAMATIC FOR SUBJECTIVE 6932 05:14:40,000 --> 05:14:45,600 EXPERIENCES PAIN FATIGUE AND 6933 05:14:45,600 --> 05:14:46,560 ANXIETY PREVALENT AND 6934 05:14:46,560 --> 05:14:48,360 DISTRESSING -- MUCH WORK DONE IN 6935 05:14:48,360 --> 05:14:52,840 THIS SPHERE HAS PREDATED 6936 05:14:52,840 --> 05:14:53,480 IMMUNOTHERAPY. 6937 05:14:53,480 --> 05:14:58,040 AS OF LATE 2022, JUST 14 STUDIES 6938 05:14:58,040 --> 05:15:00,480 IN CAR T-CELL THERAPY INCLUDED 6939 05:15:00,480 --> 05:15:02,480 PROS AND VAST MAJORITY OF THESE 6940 05:15:02,480 --> 05:15:04,320 FOCUS ON HEALTH RELATED QUALITY 6941 05:15:04,320 --> 05:15:06,440 OF LIFE AS OUTCOME AND I THINK 6942 05:15:06,440 --> 05:15:08,360 THAT ONE PREVAILING AND VERY, 6943 05:15:08,360 --> 05:15:12,360 VERY PROMISING THEME AMONG 6944 05:15:12,360 --> 05:15:14,840 STUDIES IS CAR T-CELL THERAPY 6945 05:15:14,840 --> 05:15:16,520 OFFERS FAVORABLE PATIENT 6946 05:15:16,520 --> 05:15:18,800 EXPERIENCE AND HOWEVER JUST ONE 6947 05:15:18,800 --> 05:15:20,680 STUDY WAS DONE IN CHILDREN AND 6948 05:15:20,680 --> 05:15:24,040 ONLY FOUR WERE DONE IN PATIENTS 6949 05:15:24,040 --> 05:15:26,360 WITH ACUTE LEUKEMIA AND VAST 6950 05:15:26,360 --> 05:15:28,520 MAJORITY WERE DONE WITH PATIENTS 6951 05:15:28,520 --> 05:15:33,720 WITH ADULT HEEM ATOLOGIC TYPE 6952 05:15:33,720 --> 05:15:34,480 MALIGNANCIES AND DESPITE 6953 05:15:34,480 --> 05:15:36,400 GREATEST CHANGES IN WEEKS 6954 05:15:36,400 --> 05:15:38,080 FOLLOWING TWO STUDIES COLLECTED 6955 05:15:38,080 --> 05:15:40,360 DATA IN TWO WEEKS OF INFUSION 6956 05:15:40,360 --> 05:15:43,360 AND 5 COLLECTED DATA BEYOND ONE 6957 05:15:43,360 --> 05:15:46,560 YEAR AND NOTABLY 29 OF 400 6958 05:15:46,560 --> 05:15:48,840 CURRENTLY REGISTERED CLINICAL 6959 05:15:48,840 --> 05:15:50,760 TRIALS IN CAR T-CELL THERAPY 6960 05:15:50,760 --> 05:15:53,840 AROSE IN PRIMARY OR SECONDARY 6961 05:15:53,840 --> 05:15:55,640 OUTCOME AND LONE STUDY IN 6962 05:15:55,640 --> 05:15:58,280 CHILDREN THE STUDY COLLECTED 6963 05:15:58,280 --> 05:16:00,080 LONGITUDINAL MEASURES HEALTH 6964 05:16:00,080 --> 05:16:02,600 RELATED LIFE FOLLOWING CAR 6965 05:16:02,600 --> 05:16:05,080 T-CELL THERAPY AND DOMAINS OF 6966 05:16:05,080 --> 05:16:07,040 WELL BEING IMPROVEMENT FROM 6967 05:16:07,040 --> 05:16:08,320 TREATMENT FROM BASELINE 6968 05:16:08,320 --> 05:16:11,080 OCCURRING AS EARLY AS 1 MONTH 6969 05:16:11,080 --> 05:16:13,160 POST TREATMENT SUSTAINED TO 6970 05:16:13,160 --> 05:16:15,880 THREE YEARS POST TREATMENT AND 6971 05:16:15,880 --> 05:16:19,480 PHYSICAL FUNCTION SCORES SHOWED 6972 05:16:19,480 --> 05:16:21,120 GREATEST CHANGE AND INDIVIDUALS 6973 05:16:21,120 --> 05:16:23,240 RESPONDING TO TREATMENT AND 13 6974 05:16:23,240 --> 05:16:25,000 PATIENTS COMPLETE AD ASSESSMENTS 6975 05:16:25,000 --> 05:16:28,440 AT LATER TIMEPOINTS INCLUDING 3 6976 05:16:28,440 --> 05:16:29,240 YEAR TIME POINT. 6977 05:16:29,240 --> 05:16:33,600 ONE STUDY HAS COMPARED CAR 6978 05:16:33,600 --> 05:16:34,920 T-CELL THERAPY TO AUTO 6979 05:16:34,920 --> 05:16:36,680 TRANSPLANTS AND ADULTS AND 6980 05:16:36,680 --> 05:16:38,200 PRIMARY FINDING HERE 6981 05:16:38,200 --> 05:16:40,520 DEMONSTRATED BY BLUE LINE THAT I 6982 05:16:40,520 --> 05:16:42,280 THINK IS VERY IMPORTANT AND 6983 05:16:42,280 --> 05:16:44,440 PATIENTS WHO WERE TREATED WITH 6984 05:16:44,440 --> 05:16:46,560 CARS EXPERIENCED A LESS 6985 05:16:46,560 --> 05:16:48,600 SIGNIFICANT POST TREATMENT 6986 05:16:48,600 --> 05:16:50,400 DECLINE IN WELLBEING AND QUICKER 6987 05:16:50,400 --> 05:16:53,400 RETURN TO BASELINE AND THIS IS 6988 05:16:53,400 --> 05:16:56,320 CONSISTENT ACROSS ALL DOMAINS OF 6989 05:16:56,320 --> 05:16:58,080 FUNCTIONING AND LOBBYING. 6990 05:16:58,080 --> 05:17:01,000 ONE UNPUBLISHED STUDY REPORTED 6991 05:17:01,000 --> 05:17:02,600 SYMPTOMS THAT ARE EXPERIENCED 6992 05:17:02,600 --> 05:17:05,760 FROM CARS FROM CHILD'S 6993 05:17:05,760 --> 05:17:08,320 PERSPECTIVES AND DEANNA LEVINE 6994 05:17:08,320 --> 05:17:12,120 LENT ME DATA FROM ST. JUDE PART 6995 05:17:12,120 --> 05:17:15,200 OF THIS COLLECTED ON SUBSET OF 6996 05:17:15,200 --> 05:17:16,920 PATIENTS AND CAREGIVERS FOCUSING 6997 05:17:16,920 --> 05:17:19,200 ON SYMPTOMS AND QUALITY OF LIFE 6998 05:17:19,200 --> 05:17:22,720 AT BASELINE WEEK 2 AND 4 AT CAR 6999 05:17:22,720 --> 05:17:25,560 T FUSION AND GREATEST AT WEEK 2 7000 05:17:25,560 --> 05:17:26,680 NOT SURPRISING AND MOST 7001 05:17:26,680 --> 05:17:28,520 PARTICIPANTS REPORTED A HIGH 7002 05:17:28,520 --> 05:17:29,960 NUMBER OF SYMPTOMS THROUGHOUT 7003 05:17:29,960 --> 05:17:32,960 THE TREATMENT AND QUALITY OF 7004 05:17:32,960 --> 05:17:35,840 LIFE SCORES ON OTHER HAND 7005 05:17:35,840 --> 05:17:37,000 SURPRISING REMAINED CONSISTENT 7006 05:17:37,000 --> 05:17:39,720 OVER TIME PERIOD ANALYZED 7007 05:17:39,720 --> 05:17:40,960 PSYCHOLOGICAL DISTRESS FOR 7008 05:17:40,960 --> 05:17:42,880 PARENTS AND CAREGIVERS WERE HIGH 7009 05:17:42,880 --> 05:17:44,840 THROUGHOUT THE TREATMENT AND 7010 05:17:44,840 --> 05:17:45,880 POTENTIALLY COULD HAVE EFFECTIVE 7011 05:17:45,880 --> 05:17:47,920 QUALITY OF LIFE AND IS 7012 05:17:47,920 --> 05:17:49,320 CONSISTENT ALSO WITH WHAT WE ARE 7013 05:17:49,320 --> 05:17:52,960 SEEING IN LARGER PROSPECTIVE 7014 05:17:52,960 --> 05:17:55,560 MULTI-SITE STUDY AND SUGGESTS 7015 05:17:55,560 --> 05:17:59,880 PAIN AND FATIGUE AND NAUSHIA ARE 7016 05:17:59,880 --> 05:18:01,600 PREVALENT BOTHERSOME SYMPTOMS 7017 05:18:01,600 --> 05:18:03,800 WITH INFUSION AND FIND THAT 7018 05:18:03,800 --> 05:18:05,600 SYMPTOMS ARE NOT THAT BAD AND 7019 05:18:05,600 --> 05:18:08,960 QUOTE ON QUOTE COMPARED TO 7020 05:18:08,960 --> 05:18:11,840 THERAPY AND PSYCHOSOCIAL 7021 05:18:11,840 --> 05:18:15,440 STRESSORS ARE PREVALENT AND 7022 05:18:15,440 --> 05:18:16,840 BURDEN SOME AND THIS IS 7023 05:18:16,840 --> 05:18:19,040 COMPLICATED BY MANY PATIENTS 7024 05:18:19,040 --> 05:18:21,600 WANTING SOME DEGREE OF SYMPTOM 7025 05:18:21,600 --> 05:18:23,400 RELATED SUFFERING AS REASSURANCE 7026 05:18:23,400 --> 05:18:25,320 THAT TREATMENT IS ACTUALLY 7027 05:18:25,320 --> 05:18:26,440 WORKING. 7028 05:18:26,440 --> 05:18:28,600 FINALLY LOOKING AT LONGER TERM 7029 05:18:28,600 --> 05:18:32,280 OUTCOMES ADULTS WITH MIX OF HEEM 7030 05:18:32,280 --> 05:18:37,440 ATOLOGIC MALIGNANCIES ASSESSING 7031 05:18:37,440 --> 05:18:39,080 -- ASSESSMENTS WERE 7032 05:18:39,080 --> 05:18:40,440 CROSS-SECTIONAL COMPLETED AT 1 7033 05:18:40,440 --> 05:18:43,680 TO 5 YEARS INFUSION AND 7034 05:18:43,680 --> 05:18:45,120 NONSTANDARDIZED FASHION AND 12 7035 05:18:45,120 --> 05:18:47,960 PATIENTS WENT ON TO RECEIVE BONE 7036 05:18:47,960 --> 05:18:49,680 MARROW TRANSPLANT AFTER CAR 7037 05:18:49,680 --> 05:18:51,680 T-CELL THERAPY AND REPORTED IN 7038 05:18:51,680 --> 05:18:53,320 SIGNIFICANT NUMBER OF PATIENTS 7039 05:18:53,320 --> 05:18:54,640 INCLUDING THIRD REPORTING 7040 05:18:54,640 --> 05:18:56,880 PROBLEMS WITH MEMORY OR WORD 7041 05:18:56,880 --> 05:19:00,440 FINDING AND ONE QUARTER REPORTED 7042 05:19:00,440 --> 05:19:01,040 DIFFICULTY CONCENTRATING AND 7043 05:19:01,040 --> 05:19:03,280 WANT TO NOTE THIS IS NOT 7044 05:19:03,280 --> 05:19:05,960 DEPENDENT ON WHETHER OR NOT 7045 05:19:05,960 --> 05:19:08,000 PATIENT HAD TRANSPLANT ALBEIT 7046 05:19:08,000 --> 05:19:10,600 SMALL NUMBERS COMPLAINTS ARE 7047 05:19:10,600 --> 05:19:12,800 SIMILARLY PREVALENT WITH HALF 7048 05:19:12,800 --> 05:19:14,160 PATIENTS REPORTING CLINICAL 7049 05:19:14,160 --> 05:19:16,640 NEGATIVE OUTCOME HERE YOU SEE BY 7050 05:19:16,640 --> 05:19:18,480 NONBLUE CIRCLES. 7051 05:19:18,480 --> 05:19:20,560 THIS SUGGESTS A NEED FOR MENTAL 7052 05:19:20,560 --> 05:19:23,600 HEALTH SERVICES FOLLOWING CAR 7053 05:19:23,600 --> 05:19:25,080 T-CELL THERAPY AND MOST 7054 05:19:25,080 --> 05:19:27,040 IMPORTANT FOR GROUP IS YOUNGER 7055 05:19:27,040 --> 05:19:29,920 ANL AND ACUTE NEUROTOXICITY ARE 7056 05:19:29,920 --> 05:19:31,320 LIKELY TO BE RISK FACTORS AND 7057 05:19:31,320 --> 05:19:33,760 FROM STUDIES LEARNING 7058 05:19:33,760 --> 05:19:36,400 LONGITUDINAL ASSESSMENTS PATIENT 7059 05:19:36,400 --> 05:19:39,480 REPORTED OUTCOMES ARE POSSIBLE 7060 05:19:39,480 --> 05:19:41,840 AND INCLUDING AMONG CHILDREN AND 7061 05:19:41,840 --> 05:19:43,320 PROVIDING FAVORABLE PATIENT 7062 05:19:43,320 --> 05:19:45,160 EXPERIENCE AND THERE IS ROOM FOR 7063 05:19:45,160 --> 05:19:46,200 IMPROVEMENT STILL. 7064 05:19:46,200 --> 05:19:48,160 LOOKING FORWARD, I SEE THREE 7065 05:19:48,160 --> 05:19:49,720 PRIMARY FUTURE DIRECTIONS FOR 7066 05:19:49,720 --> 05:19:52,600 PATIENT REPORTED OUTCOME 7067 05:19:52,600 --> 05:19:54,960 RESEARCH IN CAR T-CELL THERAPY. 7068 05:19:54,960 --> 05:19:56,480 FIRST, CONSENSUS AND 7069 05:19:56,480 --> 05:19:57,360 COLLABORATION IS THEME FOR TODAY 7070 05:19:57,360 --> 05:19:59,320 THAT IS E-SEINE SHL AND WE ARE 7071 05:19:59,320 --> 05:20:01,120 ALL VERY FAMILIAR WITH SAMPLE 7072 05:20:01,120 --> 05:20:03,360 SIZE LIMITATIONS INPEDIA THE 7073 05:20:03,360 --> 05:20:05,040 TRICKS AND MUST WORK TOGETHER TO 7074 05:20:05,040 --> 05:20:07,760 DO THIS WORK COLLECTING SIMILAR 7075 05:20:07,760 --> 05:20:10,600 DATA AT SIMILAR TIME POINTS 7076 05:20:10,600 --> 05:20:12,720 FOCUSING ON OTHER PATIENT 7077 05:20:12,720 --> 05:20:14,200 DOMAINS SUCH AS CAREGIVER 7078 05:20:14,200 --> 05:20:16,320 OUTCOMES AND FBL TOXICITY AND 7079 05:20:16,320 --> 05:20:18,280 SECOND COLLECTION OF DATA WITHIN 7080 05:20:18,280 --> 05:20:20,440 CONTEXT OF CLINICAL TRIAL HAS 7081 05:20:20,440 --> 05:20:22,520 BENEFITS AND ARE SUBSTANTIAL 7082 05:20:22,520 --> 05:20:24,360 LIMITATIONS PARTICULARLY WHEN 7083 05:20:24,360 --> 05:20:25,800 GENERALIZING RESULTS TO 7084 05:20:25,800 --> 05:20:28,280 PEDIATRIC PATIENTS WHO ALL 7085 05:20:28,280 --> 05:20:30,080 PEDIATRIC PATIENTS RECEIVING 7086 05:20:30,080 --> 05:20:32,400 CARS AND FINALLY DEFINING THE 7087 05:20:32,400 --> 05:20:33,520 PROBLEM IS NOT ENOUGH AND 7088 05:20:33,520 --> 05:20:35,840 APPLICATION TO PRACTICE 7089 05:20:35,840 --> 05:20:36,960 IMPROVEMENT IS NECESSARY AND 7090 05:20:36,960 --> 05:20:39,920 DATA CAN BE USED FOR GUIDING 7091 05:20:39,920 --> 05:20:41,920 ANTICIPATORY GUIDANCE WE GIVE 7092 05:20:41,920 --> 05:20:44,360 FAMILIES WITH POTENTIAL TO BE 7093 05:20:44,360 --> 05:20:46,960 LEVERAGED TO IMPROVE EARLY 7094 05:20:46,960 --> 05:20:49,240 IDENTIFICATION AND TOXICITY OF 7095 05:20:49,240 --> 05:20:52,240 EVENTS IMPROVING PATIENT CARE TO 7096 05:20:52,240 --> 05:20:55,000 IMPROVE DAY-TO-DAY QUALITY OF 7097 05:20:55,000 --> 05:20:58,440 LIFE FOR CHILDREN WITH CANCER. 7098 05:20:58,440 --> 05:20:58,960 THANK YOU. 7099 05:20:58,960 --> 05:21:01,720 >> ALL RIGHT. RUNNING A LITTLE 7100 05:21:01,720 --> 05:21:03,840 OVER AND ONE VIRTUAL 7101 05:21:03,840 --> 05:21:05,880 PRESENTATION FROM LORI MUFFLY 7102 05:21:05,880 --> 05:21:10,040 FROM STANFORD ABOUT AYA 7103 05:21:10,040 --> 05:21:20,280 POPULATION. 7104 05:22:37,360 --> 05:22:41,480 ONLY AROUND 40% OF THOSE AYAS 7105 05:22:41,480 --> 05:22:44,520 ARE TREATED IN KREVENLTERS IN 7106 05:22:44,520 --> 05:22:46,480 ADULT CANTER TREATMENT SETTING 7107 05:22:46,480 --> 05:22:49,920 AND HAS IMPLICATIONS HOW 7108 05:22:49,920 --> 05:22:52,720 PATIENTS ARE TREATING AND 7109 05:22:52,720 --> 05:22:55,560 IMPLICATIONS ON CAR T-CELLS AND 7110 05:22:55,560 --> 05:22:56,880 IMPLICATIONS TO SURVIVAL AND 7111 05:22:56,880 --> 05:23:00,000 TREATMENT PARADIGM FOR AYLL AND 7112 05:23:00,000 --> 05:23:05,040 THAT IS POSITIVE OR RELAPSE 7113 05:23:05,040 --> 05:23:08,960 REFRACTORY DIFFERS AND CURRENT 7114 05:23:08,960 --> 05:23:10,440 PARADIGM AFTER FRONTLINE THERAPY 7115 05:23:10,440 --> 05:23:12,440 AND IN ADULT WORLD WE CAN'T 7116 05:23:12,440 --> 05:23:14,680 AGREE WHETHER THAT IS AFTER 7117 05:23:14,680 --> 05:23:16,280 INDUCTION OR CONSOLIDATION 7118 05:23:16,280 --> 05:23:20,280 THERAPY AND MOST TYPICALLY FOR 7119 05:23:20,280 --> 05:23:22,680 PATIENTS RECEIVING CLEARANCE OF 7120 05:23:22,680 --> 05:23:25,400 MRD AND TRANSPLANTATION FOR 7121 05:23:25,400 --> 05:23:28,360 CONSOLIDATION AND RELAPSE 7122 05:23:28,360 --> 05:23:32,160 REFRACTORY B CELL ALL IS USED IN 7123 05:23:32,160 --> 05:23:34,160 COMBINATION WITH [INDISCERNIBLE] 7124 05:23:34,160 --> 05:23:37,920 CHEMOTHERAPY AND BLINA IS FOR 7125 05:23:37,920 --> 05:23:40,640 THOSE WITH MRD POSITIVE RELAPSE 7126 05:23:40,640 --> 05:23:44,200 AND LATE 2021 I WILL TALK ABOUT 7127 05:23:44,200 --> 05:23:45,480 WE HAVE [INDISCERNIBLE]. 7128 05:23:45,480 --> 05:23:47,840 HOWEVER, THERE IS SERIOUS 7129 05:23:47,840 --> 05:23:51,440 CHALLENGES GIVING COMMERCIAL CAR 7130 05:23:51,440 --> 05:23:53,080 T-CELLS IN ADULT TREATMENT 7131 05:23:53,080 --> 05:23:57,120 SETTING AND CHALLENGES THAT 7132 05:23:57,120 --> 05:23:58,640 PEDIATRICIANS FACE AS WELL AND 7133 05:23:58,640 --> 05:24:00,440 INSURANCE APPROVALS AND TIMING 7134 05:24:00,440 --> 05:24:02,400 OF T-CELL COLLECTION HAS BEEN AN 7135 05:24:02,400 --> 05:24:05,440 ISSUE AND WE HAVE NO MECHANISM 7136 05:24:05,440 --> 05:24:09,800 FOR PRE-EMPTIVE T-CELL PRIOR 7137 05:24:09,800 --> 05:24:11,080 PRESERVATION AND THEY DON'T TAKE 7138 05:24:11,080 --> 05:24:12,840 THESE T-CELLS FOR MANUFACTURING 7139 05:24:12,840 --> 05:24:17,960 AND IN ADULT ALL WORLD THIS 7140 05:24:17,960 --> 05:24:19,200 TRANSPLANT REMAINS PROVEN 7141 05:24:19,200 --> 05:24:20,280 [INDISCERNIBLE] AND THERE IS A 7142 05:24:20,280 --> 05:24:24,040 BIG QUESTION AS TO WHETHER CAR 7143 05:24:24,040 --> 05:24:25,600 T-CELLS ARE A DEFINITIVE THERAPY 7144 05:24:25,600 --> 05:24:27,760 ON THEIR OWN. 7145 05:24:27,760 --> 05:24:29,520 NOW, WHY DOES THE TREATMENT 7146 05:24:29,520 --> 05:24:31,720 PARADIGM DIFFER FOR AYAS TREATED 7147 05:24:31,720 --> 05:24:34,360 ON PEDIATRIC AND ADULT TREATMENT 7148 05:24:34,360 --> 05:24:37,000 SETTING AND IN PART HAS TO DO 7149 05:24:37,000 --> 05:24:39,120 WHEN DRUGS ARE APPROVED AND 7150 05:24:39,120 --> 05:24:41,360 ADULT PARADIGM OR WORLD I'M 7151 05:24:41,360 --> 05:24:45,120 TALKING ABOUT PATIENTS 18 OR 7152 05:24:45,120 --> 05:24:48,560 OLDER WE HAVE RELAPSED 7153 05:24:48,560 --> 05:24:50,840 REFRACTORY IN 2014 GOT 7154 05:24:50,840 --> 05:24:52,440 EXPERIENCED USING THIS 7155 05:24:52,440 --> 05:24:54,680 IMMUNOTHERAPY AND APPROVED IN 7156 05:24:54,680 --> 05:24:57,280 2016 AND 17 AND WASN'T APPROVED 7157 05:24:57,280 --> 05:25:00,400 UNTIL LATE 2021 AND FIRST TIME 7158 05:25:00,400 --> 05:25:02,280 ADULT PRACTITIONERS GOT HANDS ON 7159 05:25:02,280 --> 05:25:04,520 COMMERCIAL CAR T-CELL FOR ALL 7160 05:25:04,520 --> 05:25:06,680 AND PEDIATRIC TIMEFRAME LOOKS 7161 05:25:06,680 --> 05:25:08,840 DIFFERENT AND APPROVED FOR 7162 05:25:08,840 --> 05:25:10,920 PATIENTS UP TO THE AGE OF 26 AND 7163 05:25:10,920 --> 05:25:14,000 ALL THE WAY BACK IN 2016 OR 17 7164 05:25:14,000 --> 05:25:16,800 AND PEDIATRICIANS HAVE USED CAR 7165 05:25:16,800 --> 05:25:19,000 T-CELLS FOR A LONG TIME AND 7166 05:25:19,000 --> 05:25:21,360 RECENTLY STARTED TO USE THEM AND 7167 05:25:21,360 --> 05:25:23,640 HOWEVER THERE IS OTHER REASONS 7168 05:25:23,640 --> 05:25:25,840 AND THIS IS -- THESE FIGURES CAN 7169 05:25:25,840 --> 05:25:28,000 WORK FROM A SYSTEMATIC REVIEW I 7170 05:25:28,000 --> 05:25:30,520 WAS PART OF WHERE WE LOOKED AT 7171 05:25:30,520 --> 05:25:33,280 16 DIFFERENT STUDIES OF CAR 7172 05:25:33,280 --> 05:25:36,120 T-CELLS FOR ADULT B CELL ALL AND 7173 05:25:36,120 --> 05:25:38,640 INCLUDING ALMOST 500 PATIENTS. 7174 05:25:38,640 --> 05:25:40,560 YOU SEE HERE PROGRESSION FREE 7175 05:25:40,560 --> 05:25:43,160 SURVIVAL AT 12 MONTHS IS AROUND 7176 05:25:43,160 --> 05:25:44,840 37%. LOOKING AT CURVES THEY 7177 05:25:44,840 --> 05:25:47,160 DON'T LOOK ALL THAT EXCITING 7178 05:25:47,160 --> 05:25:48,440 PARTICULARLY FOR PROGRESSION 7179 05:25:48,440 --> 05:25:50,360 FREE SURVIVAL AND THERE IS A BIG 7180 05:25:50,360 --> 05:25:52,240 QUESTION ABOUT HOW ROBUST ARE 7181 05:25:52,240 --> 05:25:56,760 CAR T-CELLS FOR ADULT ALL? 7182 05:25:56,760 --> 05:26:01,720 NOW, ZUMA3 IS STUDY CONDUCTED BY 7183 05:26:01,720 --> 05:26:03,760 KITE AND BRECHLA CELL PREVIOUSLY 7184 05:26:03,760 --> 05:26:05,200 CALLED [INDISCERNIBLE] THAT LED 7185 05:26:05,200 --> 05:26:07,720 TO APPROVAL OF AGENT FOR 7186 05:26:07,720 --> 05:26:09,920 PATIENTS 18 OR OLDER YOU SEE ON 7187 05:26:09,920 --> 05:26:11,840 DIAGRAM TO THE RIGHT OF 71 7188 05:26:11,840 --> 05:26:16,840 PATIENTS ENROLLED 55 PATIENTS 7189 05:26:16,840 --> 05:26:18,800 ENFUSED AND PATIENTS REPORTED ON 7190 05:26:18,800 --> 05:26:21,520 AND USED AD LYMPHO DEPLETION YOU 7191 05:26:21,520 --> 05:26:24,360 CAN SEE DOSING OF CAR T-CELLS 7192 05:26:24,360 --> 05:26:25,840 AND 7 DAY MINIMUM 7193 05:26:25,840 --> 05:26:27,680 HOSPITALIZATION AND ARE RESULTS 7194 05:26:27,680 --> 05:26:31,560 OF SDOOUMA 3 AND 55 PATIENTS 7195 05:26:31,560 --> 05:26:34,920 INFUSED COMPOSITE CRR RATE 71% 7196 05:26:34,920 --> 05:26:37,600 AND 16% OF PATIENTS HAVE NO 7197 05:26:37,600 --> 05:26:39,160 RESPONSE AND RIGHT YOU SEE 7198 05:26:39,160 --> 05:26:41,320 MEDIAN RELAPSE SURVIVAL FOR 7199 05:26:41,320 --> 05:26:43,720 PATIENTS AND CRI WAS 14 MONTHS 7200 05:26:43,720 --> 05:26:46,200 FOR ALL TREATED PATIENTS WAS 7201 05:26:46,200 --> 05:26:48,120 APPROXIMATELY 1 YEAR AND YOU SEE 7202 05:26:48,120 --> 05:26:49,480 OVERALL SURVIVAL BELOW AND 7203 05:26:49,480 --> 05:26:51,160 FACTOR THAT SEEMED TO INFLUENCE 7204 05:26:51,160 --> 05:26:53,040 WHETHER OR NOT PATIENTS 7205 05:26:53,040 --> 05:26:55,200 RESPONDED TO THERAPY WAS 7206 05:26:55,200 --> 05:26:56,440 PERCENTAGE OF BONE MARROW BLASTS 7207 05:26:56,440 --> 05:26:58,600 AND PATIENTS WITH PACKED BONE 7208 05:26:58,600 --> 05:27:00,640 MARROW WITH PEDIATRIC RESPONSE 7209 05:27:00,640 --> 05:27:02,400 HAD MUCH LOWER RATE RESPONSES 7210 05:27:02,400 --> 05:27:07,360 AND QUITE A BIT OF TOXICITY IS 7211 05:27:07,360 --> 05:27:08,720 POST STIMULATORY CAR AND LEAD 7212 05:27:08,720 --> 05:27:13,000 CRITERIA FOR CRS AND YOU SEE 24% 7213 05:27:13,000 --> 05:27:14,080 [INDISCERNIBLE] AND NEUROTOX 7214 05:27:14,080 --> 05:27:17,800 THIS IS REALLY BEFORE ASCTC 7215 05:27:17,800 --> 05:27:20,400 GUIDELINES ARE ROUTINELY USED 7216 05:27:20,400 --> 05:27:22,720 AND GRADE 34 RATE OF NEUROTOX 7217 05:27:22,720 --> 05:27:26,840 WITH 25 P RS WITH ONE DEATH FROM 7218 05:27:26,840 --> 05:27:28,640 NEUROTOXICITY AND PEAK EXPANSION 7219 05:27:28,640 --> 05:27:32,440 WAS 15 DAYS AND DETECTED IN 20% 7220 05:27:32,440 --> 05:27:35,920 -- PCR AND 18% OF THE STUDY 7221 05:27:35,920 --> 05:27:39,160 POPULATION ACHIEVING CR 7222 05:27:39,160 --> 05:27:41,680 UNDERWENT ALOE TRANSPLANT AND 7223 05:27:41,680 --> 05:27:45,080 RELAPSE 2/3 OF PATIENTS RETAINED 7224 05:27:45,080 --> 05:27:49,520 [INDISCERNIBLE] WITH 1/3 LOSING 7225 05:27:49,520 --> 05:27:52,320 CD19 NEGATIVE RELAPSE AND LABELS 7226 05:27:52,320 --> 05:27:55,560 OF CELLS YOU SEE ARE DIFFERENT 7227 05:27:55,560 --> 05:27:57,760 IMPLICATIONS FOR AYAS WITH AGE 7228 05:27:57,760 --> 05:27:59,160 GROUPS THAT COULD GO BOTH WAYS 7229 05:27:59,160 --> 05:28:01,600 AND THEY HAVE A WIDE OPEN LABEL 7230 05:28:01,600 --> 05:28:04,800 ADULT PATIENTS 18 OR OLDER WITH 7231 05:28:04,800 --> 05:28:07,000 RELAPSE REFRACTORY B CELL AND 7232 05:28:07,000 --> 05:28:08,320 REQUIRES PATIENTS TO BE UP TO 7233 05:28:08,320 --> 05:28:12,200 AGE OF 25 AND NO OLDER THAN 25 7234 05:28:12,200 --> 05:28:14,040 AND THIS IS EITHER REFRACTORY OR 7235 05:28:14,040 --> 05:28:16,440 SECOND OR LATER RELAPSE AND 7236 05:28:16,440 --> 05:28:17,760 BRECHLA CELL COULD BE GOOD 7237 05:28:17,760 --> 05:28:20,160 OPTION FOR PATIENTS WITH FIRST 7238 05:28:20,160 --> 05:28:21,400 RELAPSE MIGHT NOT BE ABLE TO GET 7239 05:28:21,400 --> 05:28:24,520 TO THE CELL. IN ADULT A WILL. 7240 05:28:24,520 --> 05:28:26,520 L TREATMENT WORLD AND CELL 7241 05:28:26,520 --> 05:28:27,880 THERAPY TREATMENT WORLD WHAT ARE 7242 05:28:27,880 --> 05:28:32,520 WE EXCITED ABOUT? PUBLICATION 7243 05:28:32,520 --> 05:28:34,160 BY COLLEAGUES AND THIS IS ON 7244 05:28:34,160 --> 05:28:35,600 FAST CAR AND WE ARE EXCITED 7245 05:28:35,600 --> 05:28:38,440 ABOUT HERE IS NOT ONLY DO CURVES 7246 05:28:38,440 --> 05:28:40,640 LOOK GOOD BUT TOXICITY PROFILE 7247 05:28:40,640 --> 05:28:44,040 IS QUITE EXCITING WITH REALLY NO 7248 05:28:44,040 --> 05:28:48,280 GRADE 34CRS AND ONLY 15% IS 7249 05:28:48,280 --> 05:28:51,360 REPORTED IN EARLY PHASE STUDY 7250 05:28:51,360 --> 05:28:55,640 AND PHASE 1, B2 FELIX IS LIKELY 7251 05:28:55,640 --> 05:28:58,480 TO REPORT OUT BY NEXT YEAR'S 7252 05:28:58,480 --> 05:28:59,560 ASCO. WE ARE VERY MUCH HOPING 7253 05:28:59,560 --> 05:29:02,360 THIS IS A CAR THAT WILL GAIN 7254 05:29:02,360 --> 05:29:04,280 APPROVAL WITHIN THE NEXT COUPLE 7255 05:29:04,280 --> 05:29:04,800 YEARS. 7256 05:29:04,800 --> 05:29:07,880 WE ALSO HAVE BARRED OFF THE 7257 05:29:07,880 --> 05:29:09,440 WONDERFUL WORK THAT 7258 05:29:09,440 --> 05:29:11,400 PEDIATRICIANS YOUR GROUP HAS 7259 05:29:11,400 --> 05:29:13,760 DONE WITH CAR CONSORTIUM AND 7260 05:29:13,760 --> 05:29:16,680 OTHER CONSORTIUMS AND HAVE 7261 05:29:16,680 --> 05:29:18,240 OUTCOMES COLLABORATIVE OF RT AND 7262 05:29:18,240 --> 05:29:22,160 ADULT ALL CALLED ROCHA AND 14 7263 05:29:22,160 --> 05:29:24,360 CENTERS ARE INVOLVED AND 7264 05:29:24,360 --> 05:29:26,440 COUNTING AND STANFORD IS HOME 7265 05:29:26,440 --> 05:29:30,360 CENTER AND SUBMITTED THE FIRST 7266 05:29:30,360 --> 05:29:34,000 76 PATIENT EXPERIENCE TO POST 7267 05:29:34,000 --> 05:29:35,800 CARTITIS AND WE ARE EXCITED 7268 05:29:35,800 --> 05:29:36,920 ABOUT THE OPPORTUNITY AND HAVE 7269 05:29:36,920 --> 05:29:39,000 SEVERAL ABSTRACTS PLANNED FOR 7270 05:29:39,000 --> 05:29:42,000 ASH TAKING ON WONDERFUL WORK 7271 05:29:42,000 --> 05:29:48,520 THAT PEDIATRICIANS HAVE DONE AND 7272 05:29:48,520 --> 05:29:49,800 IN SUMMARY CURRENTLY TREATED IN 7273 05:29:49,800 --> 05:29:52,280 ADULT RATHER THAN PEDIATRIC 7274 05:29:52,280 --> 05:29:53,680 SETTING AND THIS IS NOT 7275 05:29:53,680 --> 05:29:55,800 UNIFORMLY CONSIDERED A 7276 05:29:55,800 --> 05:29:56,920 DESTINATION THERAPY AND 7277 05:29:56,920 --> 05:30:00,120 TREATMENT PARADIGMS B CELL ALL 7278 05:30:00,120 --> 05:30:01,920 DIFFER BETWEEN PEDIATRIC AND 7279 05:30:01,920 --> 05:30:03,760 ADULT CANCER TREATMENT SETTINGS 7280 05:30:03,760 --> 05:30:07,080 AND ADULT PRACTITIONERS TO FEEL 7281 05:30:07,080 --> 05:30:08,240 COMFORTABLE WITH DESTINATION 7282 05:30:08,240 --> 05:30:10,320 THERAPY WE NEED LONG-TERM DATA 7283 05:30:10,320 --> 05:30:12,920 AND DURABLE POST CAR REMISSIONS 7284 05:30:12,920 --> 05:30:15,760 WITHOUT USE OF CONSOLIDATIVE 7285 05:30:15,760 --> 05:30:18,280 TRANSPLANT AND IS ACCESS 7286 05:30:18,280 --> 05:30:21,440 DIFFERENT FOR AYAS TREATED ON 7287 05:30:21,440 --> 05:30:23,080 ADULT TREATMENT SETTINGS? 7288 05:30:23,080 --> 05:30:24,800 COULD BE. IS INSURANCE 7289 05:30:24,800 --> 05:30:26,240 DIFFERENT? 7290 05:30:26,240 --> 05:30:28,560 MIGHT BE. WHICH OF THESE ARE 7291 05:30:28,560 --> 05:30:31,280 LIMITING ACCESS AS WELL AND 7292 05:30:31,280 --> 05:30:32,080 PEDIATRIC CENTERS CONSIDER 7293 05:30:32,080 --> 05:30:35,320 TAKING YOUNG ADULTS WANTING CAR 7294 05:30:35,320 --> 05:30:37,320 T-CELL THERAPY AND ADVOCATES IN 7295 05:30:37,320 --> 05:30:39,640 THE PAST THE CENTERS SHOULD 7296 05:30:39,640 --> 05:30:41,600 TREAT YOUNG ADULTS OUTCOMES ARE 7297 05:30:41,600 --> 05:30:42,760 BETTER AND WE HAVE BEEN ABLE TO 7298 05:30:42,760 --> 05:30:45,520 SHOW THIS AND REACHING AYA 7299 05:30:45,520 --> 05:30:48,000 PATIENTS IN NEED AND FOR EXAMPLE 7300 05:30:48,000 --> 05:30:50,080 POOR RISK BIOLOGY WE KNOW ARE 7301 05:30:50,080 --> 05:30:51,360 REPRESENTED IN CLINICAL TRIALS 7302 05:30:51,360 --> 05:30:54,720 AND IMPORTANT AYA CENTRIC CAR 7303 05:30:54,720 --> 05:30:55,720 T-CELL QUESTIONS THAT I'M 7304 05:30:55,720 --> 05:30:58,440 EXCITED FOR US TO LOOK AT AND 7305 05:30:58,440 --> 05:31:00,120 DIFFERENTIAL TOX TIS I ACROSS 7306 05:31:00,120 --> 05:31:02,240 THE ANL SPECTRUM AND FERTILITY 7307 05:31:02,240 --> 05:31:04,040 AND LATE EFFECTS IS A NEW FIELD 7308 05:31:04,040 --> 05:31:06,080 AND SO MUCH MORE TO ANSWER AND 7309 05:31:06,080 --> 05:31:09,520 MOST EXCITING TO ME IS NOW WITH 7310 05:31:09,520 --> 05:31:14,240 APPROVAL OF BRECHLIS IS RISE IN 7311 05:31:14,240 --> 05:31:16,000 COMMERCIAL CAR T-CELL USE AMONG 7312 05:31:16,000 --> 05:31:18,160 AYAS AND USING THIS OPPORTUNITY 7313 05:31:18,160 --> 05:31:21,480 TO STUDY CAR T-CELL AS CROSS 7314 05:31:21,480 --> 05:31:23,080 THIS CONTINUUM AND REAL WORLD 7315 05:31:23,080 --> 05:31:24,400 CONSORTIUM AND YOU HAVE ONE IT 7316 05:31:24,400 --> 05:31:26,160 IS FUN TO PAIR DATA AND WORK 7317 05:31:26,160 --> 05:31:27,240 TOGETHER ON SOME OF THE 7318 05:31:27,240 --> 05:31:29,080 QUESTIONS AND WITH THAT I WILL 7319 05:31:29,080 --> 05:31:31,560 END MY TALK. I DON'T KNOW IF I 7320 05:31:31,560 --> 05:31:32,760 CAN TAKE QUESTIONS BUT WOULD BE 7321 05:31:32,760 --> 05:31:35,480 MORE THAN HAPPY TO. AGAIN, I'M 7322 05:31:35,480 --> 05:31:37,480 REALLY SORRY TO HAVE MISSED THIS 7323 05:31:37,480 --> 05:31:40,360 EXCITING EVENT. 7324 05:31:40,360 --> 05:31:41,240 THANK YOU. 7325 05:31:41,240 --> 05:31:47,800 >> >> ALL RIGHT. WE ARE 6 7326 05:31:47,800 --> 05:31:49,560 MINUTES OVER AND HAVE A BREAK 7327 05:31:49,560 --> 05:31:51,120 NOW. IF ANYONE WANTS TO STICK 7328 05:31:51,120 --> 05:31:52,760 AROUND AND TALK TO SPEAKERS OR 7329 05:31:52,760 --> 05:31:54,200 ASK QUESTIONS PEOPLE WOULD BE 7330 05:31:54,200 --> 05:31:55,840 OPEN TO STICKING AROUND BUT FEEL 7331 05:31:55,840 --> 05:31:58,400 FREE TO TAKE YOUR BREAK IF YOU 7332 05:31:58,400 --> 05:32:11,200 NEED TO. 7333 05:32:11,200 --> 05:32:14,040 >> WE ARE GETTING STARTED ON THE 7334 05:32:14,040 --> 05:32:22,400 LAST SESSION OF THE DAY. FIRST 7335 05:32:22,400 --> 05:32:27,600 SPEAKER TODAY IS RAIN ROUS WHO 7336 05:32:27,600 --> 05:32:38,640 WILL TALK TO US ABOUT TCALL. 7337 05:32:38,640 --> 05:32:42,880 >> HELLO. GOOD AFTERNOON. 7338 05:32:42,880 --> 05:32:46,400 I WILL START WITH T-CELL 7339 05:32:46,400 --> 05:32:47,640 MALIGNANCIES. THESE ARE MY 7340 05:32:47,640 --> 05:32:50,480 DISCLOESH YURZ. WE TALKED A LOT 7341 05:32:50,480 --> 05:32:57,880 ABOUT GREAT SUCCESSES WE HAVE 7342 05:32:57,880 --> 05:33:00,600 SEEN TARGETING B CELLS LEUKEMIAS 7343 05:33:00,600 --> 05:33:04,560 AND LYMPHOMAS WITH T-CELLS AND 7344 05:33:04,560 --> 05:33:06,720 THERE IS UNIQUE CHALLENGES 7345 05:33:06,720 --> 05:33:09,880 TRYING TO TARGET T-CELL 7346 05:33:09,880 --> 05:33:11,880 MALIGNANCY WITH CAR T-CELL AND 7347 05:33:11,880 --> 05:33:14,480 MANUFACTURING AND GENERATING 7348 05:33:14,480 --> 05:33:15,880 CELLS TARGETING ANCONTINUALEN 7349 05:33:15,880 --> 05:33:18,680 AND RESULT IN REALLY REMARKABLE 7350 05:33:18,680 --> 05:33:22,040 IN ANTITUMOR ACTIVITY THEY HAVE 7351 05:33:22,040 --> 05:33:26,320 A UNIQUE SET OF ISSUES THAT CAN 7352 05:33:26,320 --> 05:33:27,680 OCCUR AND ONE IS [INDISCERNIBLE] 7353 05:33:27,680 --> 05:33:30,480 CAR T-CELLS CAN ACTUALLY TARGET 7354 05:33:30,480 --> 05:33:34,480 THEMSELVES AND THEY CAN LIMIT IN 7355 05:33:34,480 --> 05:33:35,560 VITRO EXPANSION AND CAN ALSO 7356 05:33:35,560 --> 05:33:38,560 LIMIT IN VIVO ANTITUMOR ACTIVITY 7357 05:33:38,560 --> 05:33:41,080 AND T-CELLS CAN RESULT IN T-CELL 7358 05:33:41,080 --> 05:33:45,080 APLASIA AND THEY ARE TARGETING 7359 05:33:45,080 --> 05:33:51,040 T-CELL ANCONTINUALENS AND IT IS 7360 05:33:51,040 --> 05:33:54,280 MUCH LESS ACCEPTABLE SIDE 7361 05:33:54,280 --> 05:33:55,960 EFFECT. 7362 05:33:55,960 --> 05:34:00,440 LOOKING AT IDENTIFYING AN TIJEN 7363 05:34:00,440 --> 05:34:07,120 TARGETING CD7 MAINLY AND CD5 AND 7364 05:34:07,120 --> 05:34:14,280 CD30 AND AS PEDIATRICIANS WE SEE 7365 05:34:14,280 --> 05:34:16,120 PREMATURE NEOPLASMS AND GROUP 7366 05:34:16,120 --> 05:34:21,200 WAS INTERESTED IN SURINGLY 7367 05:34:21,200 --> 05:34:32,040 IDENTIFYING AN TIJANTIGENS. 7368 05:34:33,720 --> 05:34:36,400 >> WHETHER EDITED OR UNET ITDED 7369 05:34:36,400 --> 05:34:39,200 I WILL TALK ABOUT THIS. BECAUSE 7370 05:34:39,200 --> 05:34:40,720 OF SPECIFIC RISK OF 7371 05:34:40,720 --> 05:34:41,680 [INDISCERNIBLE] YOU HAVE TO 7372 05:34:41,680 --> 05:34:44,040 OFTEN EDIT OUT CD7 BY KNOCKING 7373 05:34:44,040 --> 05:34:46,960 IT OUT TO ALLOW CELLS TO EXPAND 7374 05:34:46,960 --> 05:34:49,400 IN VITRO. WE HAVE SEEN 7375 05:34:49,400 --> 05:34:50,120 REMARKABLE CLINICAL RESPONSES 7376 05:34:50,120 --> 05:34:51,800 THAT I THINK ARE GREATER THAN 7377 05:34:51,800 --> 05:34:53,640 WHAT ANY OF US EXPECTED WITH 7378 05:34:53,640 --> 05:34:56,280 NUMBER OF MRD NEGATIVE CRS AND 7379 05:34:56,280 --> 05:35:01,040 IN PATIENTS WITH IMMATURE -- 7380 05:35:01,040 --> 05:35:03,200 ALSO IMPATIENT WITH MORE MATURE 7381 05:35:03,200 --> 05:35:05,280 T-CELL LYMPHOMAS AND IMPORTANTLY 7382 05:35:05,280 --> 05:35:07,480 TRIALS ARE DESIGNED TO SERVE AS 7383 05:35:07,480 --> 05:35:09,520 A BRIDGE TO TRANSPLANT BECAUSE 7384 05:35:09,520 --> 05:35:12,400 OF RISK OF T-CELL APLASIA HE WE 7385 05:35:12,400 --> 05:35:15,800 HAVE SEEN PATIENTS IN ALL TRIALS 7386 05:35:15,800 --> 05:35:17,160 PUBLISHED AND PRESENTING 7387 05:35:17,160 --> 05:35:19,200 INFORMATION WITH ONGOING 7388 05:35:19,200 --> 05:35:21,360 COMPLETE REMISSIONS DESPITE NOT 7389 05:35:21,360 --> 05:35:22,720 PROCEEDING TO TRANSPLANT AND WE 7390 05:35:22,720 --> 05:35:27,560 HAVE LEARNED QUICKLY THAT IT IS 7391 05:35:27,560 --> 05:35:30,720 CHALLENGING TO CREATE CAR 7392 05:35:30,720 --> 05:35:34,720 T-CELLS TARGETED T-CELL ANTIGEN 7393 05:35:34,720 --> 05:35:36,080 FROM PATIENTS AND RISK IS DUE TO 7394 05:35:36,080 --> 05:35:38,480 FACT THAT WE DON'T WANT TO 7395 05:35:38,480 --> 05:35:41,880 TRANCE DEUCE MALIGNANT BLASTS 7396 05:35:41,880 --> 05:35:44,720 AND HAVING CIRCULATING 7397 05:35:44,720 --> 05:35:46,280 PERIPHERAL BLASTS AND SEVERAL 7398 05:35:46,280 --> 05:35:49,120 HAVE USED STEM CELL TRANSPLANT 7399 05:35:49,120 --> 05:35:52,160 DONOR DERIVED CAR T-CELLS 7400 05:35:52,160 --> 05:35:54,080 GENERATING FROM PRIOR TRANSPLANT 7401 05:35:54,080 --> 05:35:55,760 DONOR AND THIS CAN'T ACCOUNT FOR 7402 05:35:55,760 --> 05:35:58,920 PATIENTS UNABLE TO PROCEED TO 7403 05:35:58,920 --> 05:36:00,680 TRANSPLANTS AND OTHERS USE 7404 05:36:00,680 --> 05:36:02,280 HEALTHY DONORS AND STUDIES ARE 7405 05:36:02,280 --> 05:36:06,120 FROM CHINESE GROUPS THAT READ 7406 05:36:06,120 --> 05:36:07,840 REALLY REMARKABLE CLINICAL 7407 05:36:07,840 --> 05:36:09,840 RESPONSES WITH A NUMBER OF 7408 05:36:09,840 --> 05:36:12,560 PATIENTS BEING ABLE TO GO ON TO 7409 05:36:12,560 --> 05:36:15,000 TRANSPLANT AND SOME REMAINING IN 7410 05:36:15,000 --> 05:36:16,520 REMISSION EVEN WITHOUT 7411 05:36:16,520 --> 05:36:18,240 TRANSPLANT AND OUR GROUP FOCUSED 7412 05:36:18,240 --> 05:36:21,800 ON TARGETING CD5 AND STARTED 7413 05:36:21,800 --> 05:36:23,240 STUDY OUT WITH ON TOLL GAUS 7414 05:36:23,240 --> 05:36:25,640 STUDY AND WE ARE ABLE TO 7415 05:36:25,640 --> 05:36:27,160 GENERATE CELLS FROM VAST 7416 05:36:27,160 --> 05:36:29,560 MAJORITY OF PATIENTS AND 7417 05:36:29,560 --> 05:36:31,280 PATIENTS DESPITE BEST EFFORTS 7418 05:36:31,280 --> 05:36:33,240 UNABLE TO GENERATE SALES FROM 7419 05:36:33,240 --> 05:36:36,240 AMENDING PROTOCOL TO ALLOW US TO 7420 05:36:36,240 --> 05:36:39,360 GENERATE CD5 CAR T-CELLS FROM 7421 05:36:39,360 --> 05:36:41,440 TRANSPLANT DONOR AND SINCE THAT 7422 05:36:41,440 --> 05:36:44,120 TIME 2 OUT OF 3 PATIENTS WE 7423 05:36:44,120 --> 05:36:46,880 RETREATED ACHIEVED CDR AND ONE 7424 05:36:46,880 --> 05:36:49,120 WAS A PEDIATRIC PATIENT ABLE TO 7425 05:36:49,120 --> 05:36:52,440 GO ON TO TRANSPLANT AND PICTURES 7426 05:36:52,440 --> 05:36:56,920 WORTH 1,000 WORDS AND RECEIVING 7427 05:36:56,920 --> 05:36:58,280 LYMPHO DEPLETION STANDARDS AND 7428 05:36:58,280 --> 05:37:01,600 SINGLE INFUSION OF CD5 CAR 7429 05:37:01,600 --> 05:37:02,760 T-CELLS AND COMPLETE RESPONSE 7430 05:37:02,760 --> 05:37:04,440 AND REMARKABLE RESPONSES THAT WE 7431 05:37:04,440 --> 05:37:06,720 HAVE SEEN AND WE LEARNED LESSONS 7432 05:37:06,720 --> 05:37:09,200 AND LEARNED THAT RISKS ARE REAL 7433 05:37:09,200 --> 05:37:12,880 WHEN TARGETING T-CELL ANTIGENS 7434 05:37:12,880 --> 05:37:15,360 WITH CAR AND SAFETY PROFILE IS 7435 05:37:15,360 --> 05:37:18,040 OVERALL MANAGEABLE WITH LOW 7436 05:37:18,040 --> 05:37:22,680 GRADE CYTOKINE SYNDROME RARELY 7437 05:37:22,680 --> 05:37:25,200 SEE ANYTHING ABOVE GRADE 3 AND 7438 05:37:25,200 --> 05:37:27,160 INFECTIONS ARE REAL ISSUE 7439 05:37:27,160 --> 05:37:32,240 RELATED TO T-CELL APLASIA IN CD5 7440 05:37:32,240 --> 05:37:35,040 AND 7 T-CELLS AND WE HAVE SEEN 7441 05:37:35,040 --> 05:37:37,880 EBB POSITIVE LYMPHO 7442 05:37:37,880 --> 05:37:39,360 PROLIFERATIVE DISEASE AS RESULT 7443 05:37:39,360 --> 05:37:42,040 OF EBV REACTIVATION AND HAVE TO 7444 05:37:42,040 --> 05:37:44,240 MODIFY STUDIES TO SPECIFICALLY 7445 05:37:44,240 --> 05:37:46,440 ADDRESS THIS RISK AND COUPLE OF 7446 05:37:46,440 --> 05:37:49,640 GROUPS IN CHINA HAVE HAD TO DO 7447 05:37:49,640 --> 05:37:52,320 SO AND SEEN CRYTOPENIAS THAT ARE 7448 05:37:52,320 --> 05:37:54,440 SIMILAR TO SEEING CELLS THAT YOU 7449 05:37:54,440 --> 05:37:57,040 WILL SEE SOMETIMES OUT TO 4 OR 5 7450 05:37:57,040 --> 05:37:59,560 WEEKS AND MAIN ISSUE HAS BEEN 7451 05:37:59,560 --> 05:38:02,120 RISK OF TC APLASIA THAT HAS 7452 05:38:02,120 --> 05:38:04,560 CAUSED US TO PROPOSE SOLUTIONS 7453 05:38:04,560 --> 05:38:06,760 TO ESTABLISHED RISKS AND STUDIES 7454 05:38:06,760 --> 05:38:09,320 FOR NOW WILL REMAIN AS BRIDGE TO 7455 05:38:09,320 --> 05:38:12,160 TRANSPLANT THAT IS MAINLY A 7456 05:38:12,160 --> 05:38:14,440 SAFEGUARD AND IF YOU HAVE T-CELL 7457 05:38:14,440 --> 05:38:16,880 APLASIA AND ARE IN REMISSION AND 7458 05:38:16,880 --> 05:38:18,440 RECEIVING CONDITION IN 7459 05:38:18,440 --> 05:38:19,680 CHEMOTHERAPY MOST LIKELY THING 7460 05:38:19,680 --> 05:38:24,800 IS THAT CONDITIONING CHEMOWILL 7461 05:38:24,800 --> 05:38:25,680 ERADICATE T-CELLS AND 7462 05:38:25,680 --> 05:38:26,720 [INDISCERNIBLE] IS A MECHANISM 7463 05:38:26,720 --> 05:38:29,880 WE USED NOT JUST FOR CRS AND FOR 7464 05:38:29,880 --> 05:38:32,840 JUST FOR REFRACTORY CRS AND 7465 05:38:32,840 --> 05:38:35,480 INFLAMMATION BUT SPECIFICALLY WE 7466 05:38:35,480 --> 05:38:37,640 HAVE SEEN IT CAN KILL CAR 7467 05:38:37,640 --> 05:38:39,800 T-CELLS AND INCORPORATING 7468 05:38:39,800 --> 05:38:42,560 FREQUENT VIRAL PCR MONITORING 7469 05:38:42,560 --> 05:38:44,080 SIMILAR TO MEDIA TRANSPLANT 7470 05:38:44,080 --> 05:38:45,560 PERIOD I SUSPECT AS WE CONTINUE 7471 05:38:45,560 --> 05:38:48,720 TO TRY TO EVOLVE WITH STUDIES 7472 05:38:48,720 --> 05:38:50,640 FDA WILL BECOME SAVVY AND 7473 05:38:50,640 --> 05:38:53,120 REQUIRE YOU TO HAVE THINGS 7474 05:38:53,120 --> 05:38:55,760 TARGETING TC ANCONTINUALEN AND 7475 05:38:55,760 --> 05:38:58,120 ABENDED TRIALS AND IN ANY 7476 05:38:58,120 --> 05:39:00,760 PATIENT THAT IS EVV POSITIVE WE 7477 05:39:00,760 --> 05:39:03,200 GET THIS PRIOR TO GIVING PRIEFR 7478 05:39:03,200 --> 05:39:04,960 T-CELLS AND WE ENSURE THAT WE 7479 05:39:04,960 --> 05:39:07,440 HAVE IMMEDIATELY AVAILABLE 7480 05:39:07,440 --> 05:39:10,840 PARTIALLY HLA MATCH OFF SHELF 7481 05:39:10,840 --> 05:39:14,200 VIRUS T-CELL PRODUCT AVAILABLE 7482 05:39:14,200 --> 05:39:17,600 FOR EBV AND WE HAVE HAD PATIENTS 7483 05:39:17,600 --> 05:39:21,600 WITH EXTENSIVE EBV POSITIVE PLTD 7484 05:39:21,600 --> 05:39:23,840 THAT IS REFRACTORY TO STANDARD 7485 05:39:23,840 --> 05:39:25,760 TREATMENTS WE USE AND THERE IS A 7486 05:39:25,760 --> 05:39:28,080 BIT OF REGULATORY COMPLEXITY 7487 05:39:28,080 --> 05:39:30,320 USING GENE EDITING AND SEVERAL 7488 05:39:30,320 --> 05:39:33,080 STUDIES I HAVE SHOWN ACTUALLY 7489 05:39:33,080 --> 05:39:35,160 EDIT THEIR CAR T-CELLS TO ALLOW 7490 05:39:35,160 --> 05:39:38,240 FOR CELLS TO EXPAND IN VIVO AND 7491 05:39:38,240 --> 05:39:42,720 WHEN USING GENE EDITING IT ADDS 7492 05:39:42,720 --> 05:39:43,200 REGULATORY COMPLEXITY. 7493 05:39:43,200 --> 05:39:45,960 ONE OF THE STRATEGIES THAT OUR 7494 05:39:45,960 --> 05:39:49,200 GROUP USED THAT IS FROM THIS 7495 05:39:49,200 --> 05:39:52,160 WITH OUR GROUP IS MANUFACTURING 7496 05:39:52,160 --> 05:39:54,160 FUNCTIONAL T-CELL ANTIGEN 7497 05:39:54,160 --> 05:39:56,080 TARGETING T-CELLS WITHOUT GENE 7498 05:39:56,080 --> 05:39:59,120 EDITING RELATIVELY SIMPLE ADDING 7499 05:39:59,120 --> 05:40:01,240 CHEMICAL INHIBITION AND THIS TO 7500 05:40:01,240 --> 05:40:03,840 THE IN VITRO CULTURE THAT IS 7501 05:40:03,840 --> 05:40:06,360 ACTUALLY ENABLING CAR T-CELLS TO 7502 05:40:06,360 --> 05:40:08,320 STILL EXPAND AND TRANSLATES TO 7503 05:40:08,320 --> 05:40:10,720 ENHANCED TUMOR KILLING ALLOWING 7504 05:40:10,720 --> 05:40:13,760 US TO OPEN CD7 CAR T-CELL 7505 05:40:13,760 --> 05:40:16,080 WITHOUT USING CRISPER TO 7506 05:40:16,080 --> 05:40:18,760 KNOCKOUT CD7 AS WE ORIGINALLY 7507 05:40:18,760 --> 05:40:20,040 PLANNED AND WE LEARN THAT 7508 05:40:20,040 --> 05:40:22,760 STARTING PRODUCTS MATTER AND 7509 05:40:22,760 --> 05:40:24,120 TALKED ABOUT OFF THE SHELF 7510 05:40:24,120 --> 05:40:25,920 STRATEGIES NO THE JUST TALKING 7511 05:40:25,920 --> 05:40:27,440 ABOUT ACCESS BUT GETTING 7512 05:40:27,440 --> 05:40:28,800 THERAPIES TO ALL PATIENTS AND 7513 05:40:28,800 --> 05:40:31,200 GROUP HAS LONG HISTORY OF USING 7514 05:40:31,200 --> 05:40:33,920 VIRUS SPECIFIC T-CELLS TO TARGET 7515 05:40:33,920 --> 05:40:36,800 VIRUSES AND EBV PROLIFERATIVE 7516 05:40:36,800 --> 05:40:38,360 DISEASE AND FORTUNATE BENEFITS 7517 05:40:38,360 --> 05:40:40,200 ABOUT VIRUS SPECIFIC T-CELLS IS 7518 05:40:40,200 --> 05:40:43,240 THEY HAVE RELATIVELY LOW RISK OF 7519 05:40:43,240 --> 05:40:45,960 GRAPH VERSUS HOST DISEASE AND 7520 05:40:45,960 --> 05:40:47,880 T-CELL REPERTOIRE IS NARROW AND 7521 05:40:47,880 --> 05:40:49,560 DEFINED TO VIRUSES YOU CAN USE 7522 05:40:49,560 --> 05:40:51,800 THIS AS A PLATFORM AND WE 7523 05:40:51,800 --> 05:40:53,200 RECENTLY HAVE AN OPENED AND 7524 05:40:53,200 --> 05:40:56,880 CLINICAL TRIAL HAVING A CD30 CAR 7525 05:40:56,880 --> 05:41:00,040 ON THIS BASE IN THIS CASE EBV 7526 05:41:00,040 --> 05:41:04,720 AND LESS RISK OF GBHD AND TARGET 7527 05:41:04,720 --> 05:41:07,560 TUMORS TO CAR AND TARGET EBV 7528 05:41:07,560 --> 05:41:10,840 POSITIVE TUMORS AND HODGE KINES 7529 05:41:10,840 --> 05:41:12,320 LYMPHOMA FOR EXAMPLE POSITIVE 7530 05:41:12,320 --> 05:41:17,520 FOR EBV AND CAN POTENTIALLY 7531 05:41:17,520 --> 05:41:20,960 REJECT ALOREACTIVE T-CELLS THAT 7532 05:41:20,960 --> 05:41:23,760 UP REGULATE CD30 AND IS OPEN AND 7533 05:41:23,760 --> 05:41:25,280 ONGOING TRIAL AND I WANT TO TALK 7534 05:41:25,280 --> 05:41:27,680 ABOUT THE LESSONS LEARNED IN 7535 05:41:27,680 --> 05:41:29,680 FUTURE DIRECTIONS. WE HAVE 7536 05:41:29,680 --> 05:41:34,000 TRULY LEARNED THAT MANUFACTURED 7537 05:41:34,000 --> 05:41:35,400 CHALLENGES TRYING TO CREATE OT 7538 05:41:35,400 --> 05:41:39,080 OL GAUS PRODUCTS FOR REFRACTORY 7539 05:41:39,080 --> 05:41:41,160 T-CELL PATIENTS HAVE WIDESPREAD 7540 05:41:41,160 --> 05:41:44,600 USE LIMITED NUMBER OF HEALTHY 7541 05:41:44,600 --> 05:41:45,840 T-CELLS STARTING OFF WITH RATIO 7542 05:41:45,840 --> 05:41:49,000 OF HEALTHY T-CELLS TO 7543 05:41:49,000 --> 05:41:51,120 CONTAMINATING CIRCULATING BLASTS 7544 05:41:51,120 --> 05:41:52,680 THAT ARE [INDISCERNIBLE] AND 7545 05:41:52,680 --> 05:41:55,160 MOLECULE GENERATING T-CELLS MAY 7546 05:41:55,160 --> 05:41:57,320 IMPACT FRAT TROE CRIED MORE THAN 7547 05:41:57,320 --> 05:41:59,960 PERSISTENCE WHEN USING CAR 7548 05:41:59,960 --> 05:42:02,160 T-CELLS TYPICALLY AS BRIDGE TO 7549 05:42:02,160 --> 05:42:05,360 TRANSPLANT AND GENE EDITING OR 7550 05:42:05,360 --> 05:42:06,720 CHEMICAL INHIBITION MIGHT BE 7551 05:42:06,720 --> 05:42:09,040 NECESSARY AND NOT THE ONLY GROUP 7552 05:42:09,040 --> 05:42:10,720 TO USE A [INDISCERNIBLE] WITHIN 7553 05:42:10,720 --> 05:42:12,440 A CULTURE MECHANISM. WE KNOW 7554 05:42:12,440 --> 05:42:14,720 THIS CAN LEAD TO HAVING T-CELLS 7555 05:42:14,720 --> 05:42:16,160 THAT ARE A BIT LESS EXHAUSTED 7556 05:42:16,160 --> 05:42:18,680 AND MORE OF A CENTRAL MEMORY 7557 05:42:18,680 --> 05:42:20,360 PHENOTYPE LIKE WE TALKED ABOUT 7558 05:42:20,360 --> 05:42:22,000 EARLIER THAT ARE STRATEGIES THAT 7559 05:42:22,000 --> 05:42:24,400 HAVE TO OFTEN BE ENGAGED WHEN 7560 05:42:24,400 --> 05:42:27,640 CREATING PRODUCTS UP FRONT AND 7561 05:42:27,640 --> 05:42:28,960 CONSERVATIVE RISK MITIGATION 7562 05:42:28,960 --> 05:42:32,400 PLANNING IS KEY AND LOOKING AT 7563 05:42:32,400 --> 05:42:34,280 RISK OF INFECTIOUS COMPLICATIONS 7564 05:42:34,280 --> 05:42:37,720 AND I SUSPECT FOR ALL FUTURE 7565 05:42:37,720 --> 05:42:39,720 ITERATIONS OF CAR T-CELL TRIALS 7566 05:42:39,720 --> 05:42:42,200 AND MALIGNANCIES WE WILL BUILD 7567 05:42:42,200 --> 05:42:47,240 IN RIFBLG MITIGATION TO AVOID 7568 05:42:47,240 --> 05:42:49,200 CATASTROPHIC EVENTS AND EARLIER 7569 05:42:49,200 --> 05:42:51,200 THIS IS KEY AND RANGE RS TRUE 7570 05:42:51,200 --> 05:42:53,160 FOR ALL DISEASES WE TREAT AND 7571 05:42:53,160 --> 05:42:55,040 ALTERNATIVE DONORS ARE REALLY 7572 05:42:55,040 --> 05:42:56,480 THE FUTURE AND UNFORTUNATELY 7573 05:42:56,480 --> 05:42:58,320 MANY GROUPS INCLUDING OURS ARE 7574 05:42:58,320 --> 05:43:00,720 TRYING TO BRING THE FUTURE TO 7575 05:43:00,720 --> 05:43:03,520 NOW AND GENERATE PRODUCTS FROM 7576 05:43:03,520 --> 05:43:05,120 ALTERNATIVE DONORS AND I WILL 7577 05:43:05,120 --> 05:43:06,720 NEVER DO A PRESENTATION AGAIN 7578 05:43:06,720 --> 05:43:08,040 WITHOUT INCLUDING A SLIDE ABOUT 7579 05:43:08,040 --> 05:43:10,600 ACCESS AND IF WE CAN BUILD IT WE 7580 05:43:10,600 --> 05:43:13,880 CAN ADVOCATE FOR ACCESS WITH 7581 05:43:13,880 --> 05:43:16,320 FANCIEST CAR AND ENGINE CAN'T 7582 05:43:16,320 --> 05:43:17,600 REACH DESTINATION IF ALL ROADS 7583 05:43:17,600 --> 05:43:20,320 ARE CLOSED AND DON'T HAVE TO 7584 05:43:20,320 --> 05:43:22,240 BELABOR TO GROUPS AND PATIENTS 7585 05:43:22,240 --> 05:43:23,320 STRUGGLE WITH ACCESS TO 7586 05:43:23,320 --> 05:43:24,760 THERAPIES AND SOMETIMES MEDICAL 7587 05:43:24,760 --> 05:43:27,360 AND HEALTH CARE SYSTEMS HAVE TO 7588 05:43:27,360 --> 05:43:29,280 CATCH UP TO SCIENCE AND ACCESS 7589 05:43:29,280 --> 05:43:31,600 BARRIERS ADDRESSED AT EVERY 7590 05:43:31,600 --> 05:43:33,440 SINGLE STEP AND TRIAL CONCEPTION 7591 05:43:33,440 --> 05:43:35,160 AND IMPLEMENTATION AND TRIAL 7592 05:43:35,160 --> 05:43:37,560 ACCRUAL HAS BEGUN AND INFORMED 7593 05:43:37,560 --> 05:43:38,680 PARTICIPATION REQUIRES ALL 7594 05:43:38,680 --> 05:43:40,800 EDUCATION FOR ALL INVOLVED AND 7595 05:43:40,800 --> 05:43:42,760 SCIENTISTS PATIENTS REFERRING 7596 05:43:42,760 --> 05:43:44,080 PROVIDERS AND CLINICAL TRIAL 7597 05:43:44,080 --> 05:43:48,240 STAFF AND EQUAL ACCESS IS LANE 7598 05:43:48,240 --> 05:43:50,720 AND HOV PASS THAT IS NOT NEEDED 7599 05:43:50,720 --> 05:43:53,000 AND COMMITTEES FOR TCT AND 7600 05:43:53,000 --> 05:43:55,120 POLICY WORKING GROUPS AND WE 7601 05:43:55,120 --> 05:43:56,760 TALKED TO CONGRESS VERY OFTEN 7602 05:43:56,760 --> 05:44:00,200 AND CNS AND MEDICAID AND WE CAN 7603 05:44:00,200 --> 05:44:02,040 REALLY MAKE WAYS. I WILL BE 7604 05:44:02,040 --> 05:44:03,760 HAPPY TO TAKE QUESTIONS AND THAT 7605 05:44:03,760 --> 05:44:06,520 IS TEAM SCIENCE AND EPITOME OF 7606 05:44:06,520 --> 05:44:07,920 TEAM SCIENCE THAT I HAVE TO 7607 05:44:07,920 --> 05:44:09,720 THANK WONDERFUL PEOPLE AND 7608 05:44:09,720 --> 05:44:11,840 FUNDING SOURCES AND PATIENTS AND 7609 05:44:11,840 --> 05:44:14,280 FAMILIES AND CIGT ALUMNI THAT 7610 05:44:14,280 --> 05:44:18,040 ARE DOING GREAT THINGS IN THE 7611 05:44:18,040 --> 05:44:28,440 AUDIENCE. THANK YOU. 7612 05:44:38,960 --> 05:44:40,560 >> [APPLAUSE]. 7613 05:44:40,560 --> 05:44:42,440 >> THANK YOU VERY MUCH FOR 7614 05:44:42,440 --> 05:44:45,640 INVITATION TO SPEAK HERE AND 7615 05:44:45,640 --> 05:44:47,960 TALKING ABOUT CARDIO PEDIATRIC 7616 05:44:47,960 --> 05:44:49,680 AML AND BACKGROUND WILL BE 7617 05:44:49,680 --> 05:44:51,480 FAMILIAR YOU TO AND I WILL FOCUS 7618 05:44:51,480 --> 05:44:53,640 ON FACT THAT AS YOU ARE FAMILIAR 7619 05:44:53,640 --> 05:44:55,800 WITH MULTIPLE SHARES THAT 7620 05:44:55,800 --> 05:44:57,520 TARGETS 33 AND 123 ARE BEST 7621 05:44:57,520 --> 05:44:59,160 KNOWN AND WE WILL TALK ABOUT A 7622 05:44:59,160 --> 05:45:03,480 COUPLE TRIALS THAT ARE USING 7623 05:45:03,480 --> 05:45:03,880 THOSE. 7624 05:45:03,880 --> 05:45:06,120 THERE ARE -- THERE IS OBVIOUSLY 7625 05:45:06,120 --> 05:45:08,440 A NEED FOR NEW THERAPIES IN AML 7626 05:45:08,440 --> 05:45:11,120 SPACE AND AS YOU KNOW IT IS 7627 05:45:11,120 --> 05:45:13,920 INTENSIVE AND 50% OF PATIENTS 7628 05:45:13,920 --> 05:45:17,760 RELAPSE AND OUTCOMES FOR 7629 05:45:17,760 --> 05:45:24,520 PATIENTS FOR RELAPSE ARE POOR. 7630 05:45:24,520 --> 05:45:27,080 AML SPACE WE ARE INSPIRED WITH 7631 05:45:27,080 --> 05:45:34,280 WORK IN ALL SPACE AND. 7632 05:45:34,280 --> 05:45:37,480 THAT MEANS A DURABLE RESPONSE 7633 05:45:37,480 --> 05:45:41,040 AML CAUSES BONE MARROW APLASIA 7634 05:45:41,040 --> 05:45:43,680 THAT IS LIFE THREATENING NOT AN 7635 05:45:43,680 --> 05:45:47,640 OPTION TO STEP INTO AND NEED 7636 05:45:47,640 --> 05:45:51,600 TRANSPLANT TO RESCUE PATIENTS 7637 05:45:51,600 --> 05:45:55,280 AFTERWARDS CONSOLIDATING AND 7638 05:45:55,280 --> 05:45:57,600 TRIALS AND CAR SPACE AND THIS IS 7639 05:45:57,600 --> 05:45:59,320 PLAYING AN IMPORTANT ROLE 7640 05:45:59,320 --> 05:46:00,480 VIS-À-VIS RESPONSES WE ARE 7641 05:46:00,480 --> 05:46:02,200 SEEING THAT WE ARE NOT SEEING IN 7642 05:46:02,200 --> 05:46:04,280 A WAY THAT WOULD BE COMPARABLE 7643 05:46:04,280 --> 05:46:08,560 TO THE AML OR ALL SPACE. AS I 7644 05:46:08,560 --> 05:46:10,800 PREPARED FOR THIS TALK I WENT ON 7645 05:46:10,800 --> 05:46:14,720 CLINICAL TRIALS.GOV AND FOUND 18 7646 05:46:14,720 --> 05:46:17,080 TRIALS ENROLLED IN CHILDREN AND 7647 05:46:17,080 --> 05:46:20,040 LIST OF TARGETS THERE AND 5 7648 05:46:20,040 --> 05:46:22,000 TRIALS ARE FOR CHILDREN IN US. 7649 05:46:22,000 --> 05:46:24,440 I WILL FOCUS ON SUMMARIZING 7650 05:46:24,440 --> 05:46:29,040 TRIALS AND PIS OF TRIALS AND GOT 7651 05:46:29,040 --> 05:46:34,720 INFORMATION FOR THEM ABOUT 7652 05:46:34,720 --> 05:46:38,080 TRIALS THAT I WILL PRESENT FROM 7653 05:46:38,080 --> 05:46:39,840 THIS POINT FORWARD. 7654 05:46:39,840 --> 05:46:41,480 GENERALLY SIMILAR AND TRIALS 7655 05:46:41,480 --> 05:46:43,360 THAT ARE OPEN ONLY TO OLDER 7656 05:46:43,360 --> 05:46:44,800 CHILDREN THAT ARE REALLY RELATED 7657 05:46:44,800 --> 05:46:49,400 TO FDA APPROVAL ISSUES THAT WERE 7658 05:46:49,400 --> 05:46:52,280 NOTED BEFORE. 7659 05:46:52,280 --> 05:46:56,520 FIRST TRIAL IS CDC33 MULTI-SITE 7660 05:46:56,520 --> 05:47:00,280 TRIAL AND CD28 CONSTRUCT THAT 7661 05:47:00,280 --> 05:47:03,160 ENROLLS UP TO 34 PATIENT AND 7662 05:47:03,160 --> 05:47:06,560 INCLUDES CHLA, DENVER SEATTLE 7663 05:47:06,560 --> 05:47:11,520 AND DANA FASHER AND STANDARD 3.3 7664 05:47:11,520 --> 05:47:15,800 DESIGN AND KRUNT DOSE LEVEL -- 7665 05:47:15,800 --> 05:47:20,200 AS SINGLE INFUSION AND 22 7666 05:47:20,200 --> 05:47:23,200 PATIENTS ENROLLED WITH 19 7667 05:47:23,200 --> 05:47:25,240 PATIENTS INFUSE THE AND 1 OUT OF 7668 05:47:25,240 --> 05:47:31,400 5 VALUABLE PATIENTS DOES ELT AND 7669 05:47:31,400 --> 05:47:33,520 6TH PATIENT IS IN MIDDLE OF 7670 05:47:33,520 --> 05:47:36,480 THERAPY AND 2 OUT OF 4 PATIENTS 7671 05:47:36,480 --> 05:47:38,720 AVAILABLE AT DOSE LEVEL WITH 7672 05:47:38,720 --> 05:47:40,880 MOLECULAR CR AND ENROLLED IS 7673 05:47:40,880 --> 05:47:44,720 NEGATIVE MRD ENROLLMENT NOT 7674 05:47:44,720 --> 05:47:47,280 AVAILABLE FOR RESPONSE AND 7675 05:47:47,280 --> 05:47:49,120 CONFIDENCE INTERVAL OF THIS AND 7676 05:47:49,120 --> 05:47:52,720 DOES NOT INCLUDE ZERO THAT FOR 7677 05:47:52,720 --> 05:47:55,960 US IS IMPORTANT TAKE-HOME 7678 05:47:55,960 --> 05:48:02,680 MESSAGE AND TAKING OFF WHAT 7679 05:48:02,680 --> 05:48:07,400 RAINSAID. WE ARE HOPEFUL THAT 7680 05:48:07,400 --> 05:48:10,280 FDA WILL ALLOW US TO AMEND THIS 7681 05:48:10,280 --> 05:48:13,840 AND WILL BE INTERESTING TO SEE 7682 05:48:13,840 --> 05:48:24,160 HOW IT PLAYS OUT. 7683 05:48:30,120 --> 05:48:32,440 I BELIEVE WE TREAT THE THREE 7684 05:48:32,440 --> 05:48:35,960 PATIENTS AND NOW ARE OPEN FOR 7685 05:48:35,960 --> 05:48:39,400 PEDIATRIC ENROLLMENT THIS IS 7686 05:48:39,400 --> 05:48:44,760 INITIALLY PRESENTED BY TODAY 7687 05:48:44,760 --> 05:48:48,840 LAST YEAR AND 123 TRIAL AND CD28 7688 05:48:48,840 --> 05:48:59,400 CONSTRUCT AND CD20 SAFETY SW 7689 05:49:10,200 --> 05:49:10,360 SWITCH. 7690 05:49:10,360 --> 05:49:15,320 NO DLTS TO DATE AND ONE CR DOSE 7691 05:49:15,320 --> 05:49:18,320 LEVEL TO 2 AND PATIENT INFUSED 7692 05:49:18,320 --> 05:49:19,560 STUDY AND VERY IMPORTANT STUDIES 7693 05:49:19,560 --> 05:49:22,400 THAT HAVE COME OUT OF THIS. 7694 05:49:22,400 --> 05:49:25,640 THEY ARE A GROUP THAT AT ST. 7695 05:49:25,640 --> 05:49:27,040 JUDE'S HAS BEEN GENEROUS SHARING 7696 05:49:27,040 --> 05:49:31,880 WITH US IN CD3 TRIAL AND 7697 05:49:31,880 --> 05:49:34,240 INDICATING THAT CELLS ARE 7698 05:49:34,240 --> 05:49:35,560 PREDOMINANTLY REFACTORY CELLS 7699 05:49:35,560 --> 05:49:38,440 AND PICTURE IS WORTH 1,000 WORDS 7700 05:49:38,440 --> 05:49:41,120 AND THIS IS PREAND POST IMAGING 7701 05:49:41,120 --> 05:49:43,600 STUDY FOR A PATIENT THAT 7702 05:49:43,600 --> 05:49:44,760 EXPERIENCED A COMPLETE RESPONSE 7703 05:49:44,760 --> 05:49:48,960 TO THEIR CAR WHICH IS A VERY 7704 05:49:48,960 --> 05:49:52,720 EXCITING CLINICAL RESPONSE. 7705 05:49:52,720 --> 05:49:56,760 THERE IS CD123 TRIAL AT CHOC AND 7706 05:49:56,760 --> 05:49:58,240 BASED ON THIS CONSTRUCT THAT IS 7707 05:49:58,240 --> 05:50:00,600 DEVELOPED AT UNIVERSITY OF 7708 05:50:00,600 --> 05:50:02,520 PENNSYLVANIA AND 12 PATIENT 7709 05:50:02,520 --> 05:50:03,800 ADULT TRIAL THAT IS COMPLETED 7710 05:50:03,800 --> 05:50:06,440 AND IN PROCESS OF BEING WRITTEN 7711 05:50:06,440 --> 05:50:08,600 FOR PUBLICATION AND ARE PATIENTS 7712 05:50:08,600 --> 05:50:10,760 ON TRIAL THAT HAVE COMPLETE 7713 05:50:10,760 --> 05:50:12,640 MOLECULAR RESPONSES THAT LED TO 7714 05:50:12,640 --> 05:50:15,120 12 PATIENT TRIAL BEING OPEN AT 7715 05:50:15,120 --> 05:50:15,880 CHOC. 7716 05:50:15,880 --> 05:50:18,560 THIS IS A SINGLE DOSE LEVEL AT 7717 05:50:18,560 --> 05:50:21,280 2 x 10 TO THE 6 THAT IS MANDATED 7718 05:50:21,280 --> 05:50:24,480 BY FDA TOXICITY IS SEEN ON ADULT 7719 05:50:24,480 --> 05:50:26,600 TRIAL AND 6 VALUABLE PATIENTS 7720 05:50:26,600 --> 05:50:29,400 WITH NO DLTS AND ONE PATIENT HAD 7721 05:50:29,400 --> 05:50:32,360 A TRANSIENT DECREASE AND 7722 05:50:32,360 --> 05:50:34,720 PERFORMED BLAST AND TRANSFUSION 7723 05:50:34,720 --> 05:50:36,320 INDEPENDENCE AND NO MOLECULAR 7724 05:50:36,320 --> 05:50:38,360 RESPONSES AND ONGOING AMENDMENTS 7725 05:50:38,360 --> 05:50:40,080 TO INCREASE CELL DOSE ON THIS 7726 05:50:40,080 --> 05:50:43,080 TRIAL AND IS DERIVATIVE FROM 33 7727 05:50:43,080 --> 05:50:44,560 EXPERIENCE WHERE WE HAD TO GET 7728 05:50:44,560 --> 05:50:47,680 TO 1 x IT ENTO THE 7TH BEFORE WE 7729 05:50:47,680 --> 05:50:50,080 SEE CLINICAL EFFICACY AND BELOW 7730 05:50:50,080 --> 05:50:52,240 THAT DOSE LEVEL HERE IS THE NEXT 7731 05:50:52,240 --> 05:50:57,120 STEP FOR THIS TRIAL. 7732 05:50:57,120 --> 05:51:00,480 TEXAS CHILDREN'S HAS CLL TRIAL 7733 05:51:00,480 --> 05:51:03,880 AND TREATING UP TO 18 PATIENTS 7734 05:51:03,880 --> 05:51:07,440 WITH PEDIATRIC PATIENTS AT TEXAS 7735 05:51:07,440 --> 05:51:11,200 CHILDREN'S AND GREATER THAN 18 7736 05:51:11,200 --> 05:51:13,240 YEARS OF AGE AND PATIENTS 7737 05:51:13,240 --> 05:51:18,920 EVALUATED AT DOSE LEVEL OF 1. 7738 05:51:18,920 --> 05:51:23,320 4 OF THE 6 ARE AVAILABLE AND 7739 05:51:23,320 --> 05:51:25,880 SPECIFIC RESPONSE AVAILABLE 7740 05:51:25,880 --> 05:51:27,360 RESPONSE INFORMATION IS NOT 7741 05:51:27,360 --> 05:51:28,160 AVAILABLE AND WITH THAT THANK 7742 05:51:28,160 --> 05:51:30,720 YOU FOR ALLOWING ME TO PRESENT 7743 05:51:30,720 --> 05:51:34,600 THIS DATA OF PRIMARILY OTHER 7744 05:51:34,600 --> 05:51:43,880 PEOPLE'S WORK. 7745 05:51:43,880 --> 05:51:45,680 >> NEXT IS ROBBY WHO WILL TALK 7746 05:51:45,680 --> 05:51:50,600 TO US ABOUT CNS TUMORS. 7747 05:51:50,600 --> 05:51:52,480 >> HI, EVERYONE. NICE TO SEE 7748 05:51:52,480 --> 05:51:56,040 YOU AT THE MEETING. THANK YOU 7749 05:51:56,040 --> 05:51:58,360 TO NIRALI FOR ORGANIZING 7750 05:51:58,360 --> 05:52:01,000 FANTASTIC MEETING OF CAR T BRAIN 7751 05:52:01,000 --> 05:52:03,720 TRUST FROM BOTH SIDES OF THE 7752 05:52:03,720 --> 05:52:05,120 ATLANTIC. GREAT TO SEE. THESE 7753 05:52:05,120 --> 05:52:15,640 ARE MY DISCLOSURES PRACH IT IS 7754 05:52:18,280 --> 05:52:21,000 FUNNY I'M DOING THIS. I KNOW 7755 05:52:21,000 --> 05:52:25,400 NOTHING EXCEPT THAT BRAIN TUMORS 7756 05:52:25,400 --> 05:52:28,520 SUCK. INCURABLE INVERSE ALLEY 7757 05:52:28,520 --> 05:52:33,640 FATAL AND OTHER DISEASES APPENDO 7758 05:52:33,640 --> 05:52:37,160 MOEMA AND MEDIO BLASTOMA THEY 7759 05:52:37,160 --> 05:52:39,400 ARE TREATABLE UNTIL THEY ARE 7760 05:52:39,400 --> 05:52:41,360 RELAPSED AND THEY ARE 7761 05:52:41,360 --> 05:52:42,680 UNIVERSALLY FATAL AND WORK TO DO 7762 05:52:42,680 --> 05:52:46,600 IN THIS SPACE AND TALKING ABOUT 7763 05:52:46,600 --> 05:52:48,760 THIS SLIDE FOR A SECOND. I WANT 7764 05:52:48,760 --> 05:52:50,480 TO POINT OUT FIRST CAR T-CELL 7765 05:52:50,480 --> 05:52:54,600 EVER IN A CHILD WAS CARRIED OUT 7766 05:52:54,600 --> 05:53:03,160 BY MALCOLM BRENNER'S GROUP AND. 7767 05:53:03,160 --> 05:53:06,520 I THINK IT TAKES SOMETHING TO 7768 05:53:06,520 --> 05:53:09,760 BE BOLD ENOUGH TO DO SOMETHING 7769 05:53:09,760 --> 05:53:13,120 LIKE THIS -- HAD TWLEE OUT OF 7770 05:53:13,120 --> 05:53:14,760 11CRS AND FIRST GENERATION CAR 7771 05:53:14,760 --> 05:53:17,240 THAT HAS LED TO MULTIPLE NEW 7772 05:53:17,240 --> 05:53:19,600 ITERATIONS AND WAS A REALLY BIG 7773 05:53:19,600 --> 05:53:21,360 DEAL AND SHOWS WHAT ACADEMICS 7774 05:53:21,360 --> 05:53:23,640 CAN DO WHEN THEY ARE BOLD AND 7775 05:53:23,640 --> 05:53:25,040 TRY TO DEVELOP DRUGS 7776 05:53:25,040 --> 05:53:27,080 SPECIFICALLY FOR CHILDREN. THIS 7777 05:53:27,080 --> 05:53:29,320 IS A TARGET ALMOST IRRELEVANT IN 7778 05:53:29,320 --> 05:53:30,920 ADULT STUDIES. 7779 05:53:30,920 --> 05:53:33,240 CAR T-CELLS MAKE SENSE FOR BRAIN 7780 05:53:33,240 --> 05:53:33,520 TUMORS. 7781 05:53:33,520 --> 05:53:35,480 THEY ARE ABLE TO GET THROUGH 7782 05:53:35,480 --> 05:53:37,200 BLOOD BRAIN BARRIER. WE KNOW 7783 05:53:37,200 --> 05:53:39,760 THIS FROM EXPERIENCE WITH CD19 7784 05:53:39,760 --> 05:53:42,480 ON CAR AND ON LEFT YOU HAVE DATA 7785 05:53:42,480 --> 05:53:45,360 TREATING PATIENTS WITH PRIMARY 7786 05:53:45,360 --> 05:53:49,280 CS AND IN PEDIATRIC SPACE WE SEE 7787 05:53:49,280 --> 05:53:51,360 CAR T-CELLS TRAVEL FROM THIS 7788 05:53:51,360 --> 05:53:54,400 GROUP ALL THE TIME AND BLAST 7789 05:53:54,400 --> 05:53:56,240 COUNTDOWN AND BLACK LINES YOU 7790 05:53:56,240 --> 05:53:59,080 GET T-CELLS AND CNS BLASTS GO 7791 05:53:59,080 --> 05:54:01,680 AWAY QUICKLY AND MAKES SENSE TO 7792 05:54:01,680 --> 05:54:03,840 GIVE AWAY CAR T-CELLS THAT 7793 05:54:03,840 --> 05:54:09,240 TRAVEL ACROSS CNS. 7794 05:54:09,240 --> 05:54:12,800 I WILL JUST SHOW -- YEAH. ALL 7795 05:54:12,800 --> 05:54:15,960 RIGHT. OKAY. SO, THIS IS 7796 05:54:15,960 --> 05:54:19,240 PRECLINICAL DATA THAT WE 7797 05:54:19,240 --> 05:54:23,240 DEVELOPED OF GD2 CAR IN 7798 05:54:23,240 --> 05:54:25,240 PRECLINICAL MODELS AND 7799 05:54:25,240 --> 05:54:29,680 DISCOVERED THAT GD2 PEDIATRIC 7800 05:54:29,680 --> 05:54:31,960 TARGET FROM NEUROBLASTOMA 7801 05:54:31,960 --> 05:54:33,480 EXPRESSED ON BRAIN TUMOR THAT IS 7802 05:54:33,480 --> 05:54:36,160 DRIVEN BY EPIGENETIC MUTATION 7803 05:54:36,160 --> 05:54:38,600 AND IT WAS GREAT IN PRECLINICAL 7804 05:54:38,600 --> 05:54:40,840 MODELS AND SOME DIED EARLY ON IN 7805 05:54:40,840 --> 05:54:42,360 THE PRECLINICAL STUDIES. 7806 05:54:42,360 --> 05:54:44,680 WHAT YOU CAN SEE THERE IS IT 7807 05:54:44,680 --> 05:54:47,720 HAPPENS DURING DAY 7 TO 10 7808 05:54:47,720 --> 05:54:50,960 DURING PERIODS OF PEAK 7809 05:54:50,960 --> 05:54:53,160 INFLAMMATION AND WE FOUND IN 7810 05:54:53,160 --> 05:54:55,480 NERVE CELLS INCLUDING IN BRAIN 7811 05:54:55,480 --> 05:54:57,800 WASN'T DUE TO DESTRUCTION OF 7812 05:54:57,800 --> 05:55:02,360 NEURONS YOU FOUND ON MICE 7813 05:55:02,360 --> 05:55:03,120 HYDROCEPHALUS AND THEY WERE 7814 05:55:03,120 --> 05:55:05,800 DYING BECAUSE OF LOCATION OF THE 7815 05:55:05,800 --> 05:55:07,960 TUMORS AND BASED ON PRECLINICAL 7816 05:55:07,960 --> 05:55:10,080 STUDIES WE DESIGNED A CLINICAL 7817 05:55:10,080 --> 05:55:12,680 TRIAL I WON'T GET INTO MUCH OF 7818 05:55:12,680 --> 05:55:13,440 IT HERE. 7819 05:55:13,440 --> 05:55:15,880 WE TRIED TO USE WHATEVER WE CAN 7820 05:55:15,880 --> 05:55:18,080 GET FROM MOUSE TO GUIDE OUR 7821 05:55:18,080 --> 05:55:19,360 DEVELOPMENT AND MOST IMPORTANT 7822 05:55:19,360 --> 05:55:20,880 DECISION MADE WAS ALL PATIENTS 7823 05:55:20,880 --> 05:55:24,160 WOULD HAVE OING MIA PLACED TO 7824 05:55:24,160 --> 05:55:27,560 ACCESS CNS AND RELIEVE PRESSURE 7825 05:55:27,560 --> 05:55:32,680 BY REDUCING CSF AND BY REMOVING 7826 05:55:32,680 --> 05:55:35,480 CSF AND LOWER PRESSURE. 7827 05:55:35,480 --> 05:55:37,520 PUBLISHED AND PRESENTED TO READ 7828 05:55:37,520 --> 05:55:39,400 THE PAPER AND RESULTS FROM FIRST 7829 05:55:39,400 --> 05:55:41,480 TWO DOSE LEVELS WHERE WE TREATED 7830 05:55:41,480 --> 05:55:45,240 ABOUT 12 PATIENTS WITH 1 MILLION 7831 05:55:45,240 --> 05:55:48,360 SELLS PER KILOOR 3 MILLION CELLS 7832 05:55:48,360 --> 05:55:50,320 PER KILOAND WILL TURN YOUR 7833 05:55:50,320 --> 05:55:51,680 ATTENTION TO A COUPLE THINGS 7834 05:55:51,680 --> 05:55:54,600 THIS IS CRITERIA NOT PERFECT FOR 7835 05:55:54,600 --> 05:55:56,840 ASSESSING BRAIN TUMOR RESPONSES 7836 05:55:56,840 --> 05:56:06,000 AND WE HAD A PATIENT ON THE 7837 05:56:06,000 --> 05:56:08,840 RIGHT THERE AND SOME HAD PARTIAL 7838 05:56:08,840 --> 05:56:11,880 RESPONSES AND HIGHLIGHTING THESE 7839 05:56:11,880 --> 05:56:15,960 HERE THIS MALE RECEIVED FIRST IV 7840 05:56:15,960 --> 05:56:17,680 DOSE AND HAD PARTIAL RESPONSE TO 7841 05:56:17,680 --> 05:56:19,720 THAT DOSE AND WE HAVE FOLLOWED 7842 05:56:19,720 --> 05:56:26,240 IT UP WITH MULTIPLE ICV INFU 7843 05:56:26,240 --> 05:56:26,520 INFUSION. 7844 05:56:26,520 --> 05:56:28,560 I DON'T HAVE TIME TO GET TO IT 7845 05:56:28,560 --> 05:56:32,000 NOW STUDYING DIFFERENCE BETWEEN 7846 05:56:32,000 --> 05:56:36,280 IV AND ICV ADMINISTRATION AND 7847 05:56:36,280 --> 05:56:38,200 PATIENT HAD HUGE REDUCTION OF 7848 05:56:38,200 --> 05:56:40,600 TUMOR AND LEFT WITH BIOPSY TRACK 7849 05:56:40,600 --> 05:56:44,040 THERE AND LEFT WITH LOTS OF 7850 05:56:44,040 --> 05:56:46,080 CLINICAL IMPROVEMENTS ALSO AND 7851 05:56:46,080 --> 05:56:49,760 ACROSS PATIENTS THAT WERE 7852 05:56:49,760 --> 05:56:51,920 TREATED AND PATIENT WITH FIRST 7853 05:56:51,920 --> 05:56:54,080 YOUNG CHILD WITH DPD THAT WE 7854 05:56:54,080 --> 05:56:56,000 TREATED ON THIS TRIAL AND SHOW 7855 05:56:56,000 --> 05:56:58,560 HERE SHE HAD A VOLUMETRIC 7856 05:56:58,560 --> 05:57:00,680 INCREASE IN HER TUMOR AND PARTS 7857 05:57:00,680 --> 05:57:02,880 OF TUMOR RESPONDED. 7858 05:57:02,880 --> 05:57:05,800 YOU SEE HERE SHE HAS MID BRAIN 7859 05:57:05,800 --> 05:57:08,000 INVOLVEMENT AND SHE KEEPS HAND 7860 05:57:08,000 --> 05:57:09,880 IN SPAS TICK FLEXION AND CAN'T 7861 05:57:09,880 --> 05:57:11,440 REALLY USE IT AND WITHIN A MONTH 7862 05:57:11,440 --> 05:57:13,120 OF TREATMENT YOU CAN SEE THAT IN 7863 05:57:13,120 --> 05:57:16,080 THE CORNER OF THE MICKEY MOUSE 7864 05:57:16,080 --> 05:57:18,920 HERE YOU HAVE CLEARANCE OF TUMOR 7865 05:57:18,920 --> 05:57:21,560 AND SHE OPENS HER HAND AND 7866 05:57:21,560 --> 05:57:23,560 SPONTANEOUSLY USES IT IN PLAY 7867 05:57:23,560 --> 05:57:25,520 AND CLINICAL IMPROVEMENTS THERE 7868 05:57:25,520 --> 05:57:26,880 ARE LOTS OF AT SAME TIME AND 7869 05:57:26,880 --> 05:57:28,880 VIDEO TELLS IT THE BEST AND WHEN 7870 05:57:28,880 --> 05:57:30,720 SHE CAME INTO CLINIC FOR 7871 05:57:30,720 --> 05:57:33,640 ENROLLMENT SHE HAD TO WALK WITH 7872 05:57:33,640 --> 05:57:34,720 PARENTAL ASSISTANCE AND THIS IS 7873 05:57:34,720 --> 05:57:42,800 HER AFTER 2 MONTHS OF INFUSION. 7874 05:57:42,800 --> 05:57:45,280 THIS LASTED A COUPLE MONTHS 7875 05:57:45,280 --> 05:57:47,360 UNTIL SHE EVENTUALLY PROGRESSED 7876 05:57:47,360 --> 05:57:50,240 AND TRIED TO TREAT HER WITH ICV 7877 05:57:50,240 --> 05:57:51,960 AND HAS BEEN UNSUCCESSFUL AND 7878 05:57:51,960 --> 05:57:56,440 OKAY WITH PATIENTS ON TRIAL AND 7879 05:57:56,440 --> 05:57:57,920 TRANSIENT BENEFIT LASTING 7880 05:57:57,920 --> 05:58:00,040 SEVERAL MONTHS AND TELLS YOU WE 7881 05:58:00,040 --> 05:58:03,120 ARE STARTING AND UNBELIEVABLE IT 7882 05:58:03,120 --> 05:58:04,920 WORKS AS WELL AND MEDIATING 7883 05:58:04,920 --> 05:58:06,720 RESPONSE AND WE ARE CLEARLY NOT 7884 05:58:06,720 --> 05:58:08,760 THERE AND NOT CURING OR COMING 7885 05:58:08,760 --> 05:58:10,360 CLOSE TO CURING ANY PATIENTS AND 7886 05:58:10,360 --> 05:58:12,760 WE ARE NOT ONLY ONES IN THE 7887 05:58:12,760 --> 05:58:15,640 CLINIC DOING CAR T-CELLS AND 7888 05:58:15,640 --> 05:58:18,160 THERE IS AT LEAST THREE OTHER 7889 05:58:18,160 --> 05:58:20,040 GROUPS ACTIVELY EXPLORING THIS 7890 05:58:20,040 --> 05:58:22,560 IN PEDIATRIC DISEASES AND ARE 7891 05:58:22,560 --> 05:58:25,680 GROUPS AND SLIDES FROM MINA HEG 7892 05:58:25,680 --> 05:58:28,800 DAY AND GROUP FROM BAYLOR AND 7893 05:58:28,800 --> 05:58:32,560 THIS IS STEVE GOD CHALK 7894 05:58:32,560 --> 05:58:35,680 PUBLISHING AND YOU SEE RESPONSE 7895 05:58:35,680 --> 05:58:38,720 HERE IN PATIENTS THAT WERE 7896 05:58:38,720 --> 05:58:40,760 STABLE PROGRESSIVE DISEASE ON 7897 05:58:40,760 --> 05:58:41,960 TRIAL AND NEXT GENERATION 7898 05:58:41,960 --> 05:58:44,480 VERSION OF TRIAL GOING FORWARD 7899 05:58:44,480 --> 05:58:46,680 IN MULTITENOR TRIAL BRINGING 7900 05:58:46,680 --> 05:58:50,920 THIS TO PATIENTS WITH PEN DAH 7901 05:58:50,920 --> 05:58:54,600 MOEMA THAT IS BEST PLACE TO GO 7902 05:58:54,600 --> 05:58:57,160 THIS THROUGH PBTC IS OPENED NOW 7903 05:58:57,160 --> 05:59:01,680 AT MULTIPLE CENTERS. 7904 05:59:01,680 --> 05:59:08,720 THIS IS WORK FROM CITY OF HOPE 7905 05:59:08,720 --> 05:59:12,800 TWO CAR T-CELLS WITH RESULTS OF 7906 05:59:12,800 --> 05:59:13,920 REPORTING IN NEW ENGLAND JOURNAL 7907 05:59:13,920 --> 05:59:16,680 5 OR 6 YEARS AGO INCLUDING A 7908 05:59:16,680 --> 05:59:18,800 COMPLETE RESPONSE WITH ADULTS 7909 05:59:18,800 --> 05:59:21,160 WITH [INDISCERNIBLE] AND TAKING 7910 05:59:21,160 --> 05:59:23,480 OPPORTUNITY TO ASK AN IMPORTANT 7911 05:59:23,480 --> 05:59:25,440 QUESTION AND THEY ARE ADDING 7912 05:59:25,440 --> 05:59:29,000 LYMPHO DEPLETION AND HAVE DONE 7913 05:59:29,000 --> 05:59:29,960 PATIENTS WITHOUT LYMPHO 7914 05:59:29,960 --> 05:59:32,920 DEPLETION AND WE ARE NOW IN 7915 05:59:32,920 --> 05:59:35,480 COHORT WITH LYMPHO DEPLETION AND 7916 05:59:35,480 --> 05:59:37,440 RESULTS OF FIRST THREE PATIENTS 7917 05:59:37,440 --> 05:59:42,200 YOU HAVE IN BLUE A PEN DAH MOEMA 7918 05:59:42,200 --> 05:59:45,520 PATIENT. THIS IS A 7919 05:59:45,520 --> 05:59:47,760 [INDISCERNIBLE] PATIENT AND THIS 7920 05:59:47,760 --> 05:59:50,520 IS A DAH MOEMA PATIENT AND 7921 05:59:50,520 --> 05:59:52,240 LOOKING FORWARD TO SEEING DATA 7922 05:59:52,240 --> 05:59:54,600 SOON WITH LD. THIS IS 7923 05:59:54,600 --> 05:59:58,120 INCREDIBLE PORTFOLIO OF TRIALS 7924 05:59:58,120 --> 05:59:59,640 FROM SEATTLE CHILDREN'S. THESE 7925 05:59:59,640 --> 06:00:02,600 SLIDES AND UP IN BLUE YOU CAN 7926 06:00:02,600 --> 06:00:04,520 SEE THERE ARE MANY TRIALS THEY 7927 06:00:04,520 --> 06:00:06,600 ARE DOING IN BRAIN TUMORS AND 7928 06:00:06,600 --> 06:00:08,280 PUSHING THE ENVELOPE FOR KIDS 7929 06:00:08,280 --> 06:00:10,680 HERE. I WILL SHOW DATA FROM 7930 06:00:10,680 --> 06:00:13,560 PUBLISHED DATA AND FIRST THEY 7931 06:00:13,560 --> 06:00:15,520 PUBLISHED HER 2 CAR THREE 7932 06:00:15,520 --> 06:00:17,360 PATIENTS IN NATURE MEDICINE AND 7933 06:00:17,360 --> 06:00:19,480 SEE THEY ARE SHOWING DURING 7934 06:00:19,480 --> 06:00:21,600 INFUSION YOU SEE EVIDENCE OF 7935 06:00:21,600 --> 06:00:22,960 LOCAL INFLAMMATION AND CELLS ARE 7936 06:00:22,960 --> 06:00:24,800 TRAVELING THERE AND DOING 7937 06:00:24,800 --> 06:00:27,560 SOMETHING. PATIENT EVENTUALLY 7938 06:00:27,560 --> 06:00:29,160 PROGRESSED AND IN RECENT 7939 06:00:29,160 --> 06:00:31,680 PUBLICATION OF P7H3 CAR WHERE 7940 06:00:31,680 --> 06:00:34,760 THEY GIVE LOCAL ADMINISTRATION I 7941 06:00:34,760 --> 06:00:37,600 WILL SEE ABOUT 20% SHRINKAGE OF 7942 06:00:37,600 --> 06:00:39,800 SIZE OF TUMOR OF IT THIS PATIENT 7943 06:00:39,800 --> 06:00:41,760 AND THEY ARE MOVING ON FROM 7944 06:00:41,760 --> 06:00:44,560 TRIALS AND NOW STARTING 7945 06:00:44,560 --> 06:00:48,080 MULTIANTIGEN TARGETING APPROACH 7946 06:00:48,080 --> 06:00:52,960 AND PROVEN HER 2 -- ALSO ADDING 7947 06:00:52,960 --> 06:00:57,160 TO THAT IL-7 TAENRECEPTOR TOO. 7948 06:00:57,160 --> 06:01:01,600 AN TIJENS WILL BE IMPORTANT IN 7949 06:01:01,600 --> 06:01:03,200 HETEROGENOUS DISEASES HOW AM I 7950 06:01:03,200 --> 06:01:06,040 DOING ON TIME? 7951 06:01:06,040 --> 06:01:12,280 OKAY. LY SAY A COUPLE WORDS 7952 06:01:12,280 --> 06:01:16,440 ABOUT THIS NEW ACCESS OF 7953 06:01:16,440 --> 06:01:16,880 TOXICITY. 7954 06:01:16,880 --> 06:01:19,320 ONE THING WE FOUND WE TREATED 7955 06:01:19,320 --> 06:01:21,160 PATIENTS WITH BRAIN STEM TUMORS 7956 06:01:21,160 --> 06:01:22,920 GETTING INFLAMMATION IN BRAIN 7957 06:01:22,920 --> 06:01:24,480 TUMOR AND TAUGHT US IT IS THE 7958 06:01:24,480 --> 06:01:26,160 BRAIN AND IT ACTUALLY DOES STUFF 7959 06:01:26,160 --> 06:01:28,320 AND YOU SEE SYMPTOMS BASED ON 7960 06:01:28,320 --> 06:01:30,240 WHERE THE TUMOR IS IN THE BRAIN 7961 06:01:30,240 --> 06:01:33,240 AND YOU SOMETIMES SEE WORSENING 7962 06:01:33,240 --> 06:01:38,720 OF BASELINE DEFICITS PATIENT HAS 7963 06:01:38,720 --> 06:01:45,240 AND CRANIOPATHY GETS WORSE AND 7964 06:01:45,240 --> 06:01:46,080 SELF-RESOLVES NOT SOMETHING TO 7965 06:01:46,080 --> 06:01:47,920 DO SOMETHING ABOUT AND THIS CAN 7966 06:01:47,920 --> 06:01:53,200 PRESENT AS LIFE THREATENING 7967 06:01:53,200 --> 06:01:54,480 HYDROCEPHALOUS AND DOES CLINICAL 7968 06:01:54,480 --> 06:01:57,360 WORK ON GROUND TAKING CARE OF 7969 06:01:57,360 --> 06:01:59,080 PATIENTS THAT DEVELOPED GRADING 7970 06:01:59,080 --> 06:02:02,960 SCALE FOR TN THAT WILL BE 7971 06:02:02,960 --> 06:02:03,880 PUBLISHED SOON IN NATURE 7972 06:02:03,880 --> 06:02:06,200 MEDICINE DOING COLLABORATIVE 7973 06:02:06,200 --> 06:02:08,040 EFFORT WITH GROUPS FROM AROUND 7974 06:02:08,040 --> 06:02:14,240 THE WORLD TREATING PATIENTS WITH 7975 06:02:14,240 --> 06:02:16,840 TNS MODELS. 7976 06:02:16,840 --> 06:02:19,320 CONCLUDING CAR T-CELLS REALLY 7977 06:02:19,320 --> 06:02:20,760 THERE IS A STRONG OPPORTUNITY 7978 06:02:20,760 --> 06:02:25,560 FOR THEM TO SHOW EFFICACY IN 7979 06:02:25,560 --> 06:02:27,080 PEDIATRIC BRAIN TUMORS WHERE 7980 06:02:27,080 --> 06:02:28,920 NOTHING ELSE WORKED AND MOST 7981 06:02:28,920 --> 06:02:33,840 THINGS DON'T GET TO CNS. TNS 7982 06:02:33,840 --> 06:02:35,360 EMERGED ACCESS TO TUMOR LOCATION 7983 06:02:35,360 --> 06:02:37,720 AND MULTIPLE CLINICAL TRIALS 7984 06:02:37,720 --> 06:02:40,040 HAPPENING AT MULTIPLE CENTERS 7985 06:02:40,040 --> 06:02:41,640 POINTING OUT THIS MORNING THAT 7986 06:02:41,640 --> 06:02:44,880 THERE IS A NICE JOB SHOWING HUGE 7987 06:02:44,880 --> 06:02:48,040 LANDSCAPE OF CAR T-CELLS GOING 7988 06:02:48,040 --> 06:02:50,680 ON IN BIOTECH LOCATED IN 7989 06:02:50,680 --> 06:02:52,560 BACKYARD IN PALO ALTO AND 7990 06:02:52,560 --> 06:02:54,280 PUSHING COMPANIES TO DO 7991 06:02:54,280 --> 06:02:56,280 PEDIATRIC TRIALS AND AGREE WITH 7992 06:02:56,280 --> 06:02:58,080 THEM ADDING MOST COMPANIES WON'T 7993 06:02:58,080 --> 06:02:59,600 DO PEDIATRIC TRIALS WHATEVER YOU 7994 06:02:59,600 --> 06:03:02,040 TELL THEM. THEY ARE VENTURE 7995 06:03:02,040 --> 06:03:04,120 BACKED AND DOESN'T MAKE SENSE 7996 06:03:04,120 --> 06:03:05,560 FOR THEM TO DO IT. 7997 06:03:05,560 --> 06:03:09,360 THERE IS 3 IMMUNOTHERAPIES 7998 06:03:09,360 --> 06:03:12,280 APPROVED AND CHIMERA DID 7999 06:03:12,280 --> 06:03:13,560 [INDISCERNIBLE] AND EVERY SINGLE 8000 06:03:13,560 --> 06:03:15,880 ONE OF THOSE I WANT TO REMIND 8001 06:03:15,880 --> 06:03:18,400 EVERYONE WERE DERISKED IN 8002 06:03:18,400 --> 06:03:20,640 ACADEMIA AND INITIAL TRIALS WERE 8003 06:03:20,640 --> 06:03:22,680 RUN IN ACADEMIA SHOWING ACTIVITY 8004 06:03:22,680 --> 06:03:26,000 IN IT AT THAT POINT SHOWING 8005 06:03:26,000 --> 06:03:28,160 BIOTECH AND LARGER PHARMA CAME 8006 06:03:28,160 --> 06:03:30,320 IN AND SHOWED DRUGS AND 8007 06:03:30,320 --> 06:03:33,960 RESPONSIBILITY ON US IS ACADEMIC 8008 06:03:33,960 --> 06:03:35,920 PEDIATRIC ONCOLOGIES RUNNING 8009 06:03:35,920 --> 06:03:38,720 PHASE 1 TRIALS IN ACADEMIA 8010 06:03:38,720 --> 06:03:41,280 PROVING BENEFIT THERE AND 8011 06:03:41,280 --> 06:03:42,520 DRIVING INVESTMENT. 8012 06:03:42,520 --> 06:03:45,800 AND HOPEFULLY WE WILL HAVE MORE 8013 06:03:45,800 --> 06:03:47,440 EFFICACIOUS CARS AND LEARN FROM 8014 06:03:47,440 --> 06:03:48,920 CLINICAL TRIALS AND CONTINUE TO 8015 06:03:48,920 --> 06:03:50,960 DEVELOP THEM AND I LOST 8016 06:03:50,960 --> 06:03:52,040 ACKNOWLEDGEMENT SLIDE AND 8017 06:03:52,040 --> 06:03:54,680 ACKNOWLEDGING AMAZING GROUP AT 8018 06:03:54,680 --> 06:03:56,680 STANFORD DRIVING CLINICAL WORK 8019 06:03:56,680 --> 06:03:58,880 AND OF COURSE OUR PATIENTS ARE 8020 06:03:58,880 --> 06:04:00,760 FAMILIES AND OTHER GROUPS 8021 06:04:00,760 --> 06:04:02,680 CONTRIBUTING THOSE SLIDES AND 8022 06:04:02,680 --> 06:04:05,600 ARE DOING EXCELLENT CLINICAL 8023 06:04:05,600 --> 06:04:10,600 WORK ALSO. 8024 06:04:10,600 --> 06:04:13,800 >> LAST SPEAKER FOR SESSION DR. 8025 06:04:13,800 --> 06:04:17,600 ROSA WIN WILL TALK TO US ABOUT 8026 06:04:17,600 --> 06:04:20,600 SOLID TUMORS. 8027 06:04:20,600 --> 06:04:23,000 >> GOOD AFTERNOON, EVERYONE. 8028 06:04:23,000 --> 06:04:25,440 I'M ROSA. THANK YOU FOR GIVING 8029 06:04:25,440 --> 06:04:26,960 ME THE OPPORTUNITY TO CONTRIBUTE 8030 06:04:26,960 --> 06:04:29,320 TO THIS SESSION. I'M PART OF 8031 06:04:29,320 --> 06:04:32,360 POB TEAM AND RUN A LAB HERE AND 8032 06:04:32,360 --> 06:04:34,680 TRANSLATE FINDINGS FROM LAB TO 8033 06:04:34,680 --> 06:04:37,240 CLINIC. WASN'T TASKED TO TALK 8034 06:04:37,240 --> 06:04:38,680 ABOUT EXPANDING USE OF CAR 8035 06:04:38,680 --> 06:04:40,480 T-CELLS AND SOLID TUMORS THAT 8036 06:04:40,480 --> 06:04:43,120 FOR 8 MINUTES IS A LOT AND HOPE 8037 06:04:43,120 --> 06:04:45,960 YOU CAN USE PROMPTERS FOR TALK 8038 06:04:45,960 --> 06:04:47,760 IN FURTHER DISCUSSION. WHEN I 8039 06:04:47,760 --> 06:04:51,280 PUT THIS TOGETHER I REVIEWED 8040 06:04:51,280 --> 06:04:52,200 CURRENT TRIALS THAT HAVE BEEN 8041 06:04:52,200 --> 06:04:54,080 COMPLETED AND LISTED THEM ALL 8042 06:04:54,080 --> 06:04:55,920 HERE. WHAT BECOMES VERY CLEAR 8043 06:04:55,920 --> 06:04:59,160 IS THAT MOST OF THE SOLID TUMOR 8044 06:04:59,160 --> 06:05:00,440 TRIALS THAT HAVE BEEN COMPLETED 8045 06:05:00,440 --> 06:05:03,800 HAVE BEEN DONE IN PATIENTS WITH 8046 06:05:03,800 --> 06:05:05,200 NEUROMRAFTOMA AND HANDFUL OF 8047 06:05:05,200 --> 06:05:08,120 DIFFERENT SAR COMBAS AT BOTTOM 8048 06:05:08,120 --> 06:05:10,120 AND MAIN TARGET PEOPLE HAVE 8049 06:05:10,120 --> 06:05:12,360 LOOKED AT IS GD2. YOU HAVE 8050 06:05:12,360 --> 06:05:16,840 DIFFERENT ITERATIONS OF CARS 8051 06:05:16,840 --> 06:05:22,800 RANGING FROM MUIRIN TO HUMANIZED 8052 06:05:22,800 --> 06:05:24,560 CRVS TO DIFFERENT GENERATIONS 8053 06:05:24,560 --> 06:05:26,520 AND PLATFORMS AND WANT TO POINT 8054 06:05:26,520 --> 06:05:28,880 OUT HERE THAT IF YOU LOOK AT 8055 06:05:28,880 --> 06:05:31,000 RESPONSES AND NUMBERS THEY WILL 8056 06:05:31,000 --> 06:05:33,280 FIRST OF ALL ALTER OR BE 8057 06:05:33,280 --> 06:05:34,960 DIFFERENT COMPARED TO ABSTRACTS 8058 06:05:34,960 --> 06:05:37,440 WHEN YOU PULL PAPERS AND LOTS OF 8059 06:05:37,440 --> 06:05:39,400 PATIENTS ARE INCLUDED IN TRIALS 8060 06:05:39,400 --> 06:05:41,520 THAT HAVE NO DISEASE OR 8061 06:05:41,520 --> 06:05:42,720 MEASURABLE DISEASE AT TIME 8062 06:05:42,720 --> 06:05:43,960 INFUSION THAT IS A LITTLE BIT 8063 06:05:43,960 --> 06:05:45,600 DIFFICULT TO SEE WHAT EFFECT OF 8064 06:05:45,600 --> 06:05:47,720 CAR T-CELLS WOULD BE AND 8065 06:05:47,720 --> 06:05:49,520 NARROWED IT DOWN TO JUST 8066 06:05:49,520 --> 06:05:50,720 MEASURABLE DISEASE THAT YOU CAN 8067 06:05:50,720 --> 06:05:52,960 SEE THAT IN FACT WE REALLY ONLY 8068 06:05:52,960 --> 06:05:56,600 HAD 2CRS THAT IS VERY 8069 06:05:56,600 --> 06:05:57,720 CONTRASTING AND DIVERGIENT IF WE 8070 06:05:57,720 --> 06:06:00,120 THINK ABOUT ALL OF THE SUCCESSES 8071 06:06:00,120 --> 06:06:04,080 IN B CELL HEEM ATOLOGIC 8072 06:06:04,080 --> 06:06:06,360 MALIGNANCY WORLD AND POINTING 8073 06:06:06,360 --> 06:06:08,640 OUT ALSO TWO CRS ARE MAINLY IN 8074 06:06:08,640 --> 06:06:11,520 TWO PATIENTS WITH VERY LIMITED 8075 06:06:11,520 --> 06:06:15,560 DISEASE BURDEN ONLY TO BONY 8076 06:06:15,560 --> 06:06:16,480 LESIONS. 8077 06:06:16,480 --> 06:06:18,760 LOOKING AT TRIALS THAT ARE 8078 06:06:18,760 --> 06:06:22,320 CURRENTLY OPEN, IN THE US AND IN 8079 06:06:22,320 --> 06:06:25,840 EUROPE. I LEFT OUT ASIA. JUST 8080 06:06:25,840 --> 06:06:28,920 THESE TWO REGIONS YOU SEE A 8081 06:06:28,920 --> 06:06:31,160 MULTITUDE OF DIFFERENT TRIALS 8082 06:06:31,160 --> 06:06:32,600 AND AGAIN A LARGE REPRESENTATION 8083 06:06:32,600 --> 06:06:34,520 OF GD2 AND DON'T KNOW IF SOME OF 8084 06:06:34,520 --> 06:06:41,160 YOU HAVE ATTENDED THE EUROPEAN 8085 06:06:41,160 --> 06:06:43,040 HEMATOLOGY ASSOCIATION MEETING 8086 06:06:43,040 --> 06:06:45,440 LAST MONTH WHERE ITALIAN GROUP 8087 06:06:45,440 --> 06:06:46,280 PRESENTED FINDINGS AND I THINK 8088 06:06:46,280 --> 06:06:49,840 THAT THE PAPER IS ACCEPTED IN 8089 06:06:49,840 --> 06:06:51,480 NEW ENGLAND JOURNAL OF MEDICINE 8090 06:06:51,480 --> 06:06:54,320 AND REPORTED TWO-YEAR EVENT 8091 06:06:54,320 --> 06:06:57,080 SURVIVAL OF 44% AND AMAZING 8092 06:06:57,080 --> 06:06:58,480 CAN'T WAIT TO READ PAPER SEEING 8093 06:06:58,480 --> 06:07:00,640 WHAT DIFFERENCES ARE IN THIS 8094 06:07:00,640 --> 06:07:02,360 TRIAL COMPARED TO WHAT WE KNOW 8095 06:07:02,360 --> 06:07:06,040 ABOUT G2 AND WHAT HAS BEEN 8096 06:07:06,040 --> 06:07:06,320 REPORTED. 8097 06:07:06,320 --> 06:07:08,200 WE WILL USE THE REST OF THE TIME 8098 06:07:08,200 --> 06:07:10,640 ACTUALLY TO TALK ABOUT UNIQUE 8099 06:07:10,640 --> 06:07:13,640 CHALLENGES OF CAR T-CELLS AND 8100 06:07:13,640 --> 06:07:17,480 SOLID TUMORS AND WHY WE HAVEN'T 8101 06:07:17,480 --> 06:07:20,880 BEEN SUCCESSFUL COMPARED TO 8102 06:07:20,880 --> 06:07:25,240 COLLEAGUES IN LUKE WORLD AND 8103 06:07:25,240 --> 06:07:31,400 LISTED FOUR IMPORTANT ONES HERE. 8104 06:07:31,400 --> 06:07:34,480 WE HAVE TUMOR HETEROGENEITY THAT 8105 06:07:34,480 --> 06:07:37,040 I ARGUE WE DEAL WITH IN LUKEMIA 8106 06:07:37,040 --> 06:07:41,200 AND IN THIS CONTEXT IS REALLY 8107 06:07:41,200 --> 06:07:42,920 SPATIALLY CONFINED WHEN T-CELLS 8108 06:07:42,920 --> 06:07:49,080 COMELE INTO THE PATIENT BODY AND 8109 06:07:49,080 --> 06:07:51,040 HOME TO TUMOR SITE THEY ARE 8110 06:07:51,040 --> 06:07:53,840 OUTNUMBERED BY TUMOR CELLS AND 8111 06:07:53,840 --> 06:07:57,160 IF THEY GET INTO THE TUMOR 8112 06:07:57,160 --> 06:07:58,920 MICROENVIRONMENT THEY ARE 8113 06:07:58,920 --> 06:08:01,640 NUTRIENT DEPRIVED AND CYTOKINE 8114 06:08:01,640 --> 06:08:03,920 DEPRIVED AND ENCOUNTER IMMUNE 8115 06:08:03,920 --> 06:08:05,520 CHECK POINTS AND DIFFICULT FOR 8116 06:08:05,520 --> 06:08:07,040 THEM TO SURVIVE AND FUNCTION AND 8117 06:08:07,040 --> 06:08:10,360 BIG QUESTION IS HOW TO OVERCOME 8118 06:08:10,360 --> 06:08:13,000 CHALLENGES OF CURRENT CAR T-CELL 8119 06:08:13,000 --> 06:08:15,080 THERAPIES AGAINST SOLID TUMORS 8120 06:08:15,080 --> 06:08:16,400 AND MOST WORK HAS BEEN DONE OR 8121 06:08:16,400 --> 06:08:19,440 IS ONGOING IN PRECLINICAL REALM 8122 06:08:19,440 --> 06:08:21,520 THAT HASN'T BEEN TRANSLATED YET. 8123 06:08:21,520 --> 06:08:25,320 I WILL JUST PUT UP A COUPLE OF 8124 06:08:25,320 --> 06:08:26,680 EXAMPLES TO STIMULATE THE 8125 06:08:26,680 --> 06:08:27,920 DISCUSSION AND ONE OF THE 8126 06:08:27,920 --> 06:08:32,120 STRATEGIES IS LOOKING AT THE 8127 06:08:32,120 --> 06:08:35,000 SCARCITY OF OR LACK OF TUMOR 8128 06:08:35,000 --> 06:08:36,720 SPECIFIC ANTIGENS THAT IS 8129 06:08:36,720 --> 06:08:39,600 ACTUALLY THIS STORY HERE THAT IS 8130 06:08:39,600 --> 06:08:43,480 GPC2 AND THIS IS A GLOPOKIN AND 8131 06:08:43,480 --> 06:08:45,640 THREE UPCOMING TRIALS AT 8132 06:08:45,640 --> 06:08:52,160 STANFORD AND NCI AND GPTC2 IS A 8133 06:08:52,160 --> 06:08:55,360 HEAVY ONCO FETAL PROTEIN 8134 06:08:55,360 --> 06:08:56,960 DOWNREGULATED AND MATURE TISSUES 8135 06:08:56,960 --> 06:09:00,800 YOU WILL FIND IN TESTES AND SOME 8136 06:09:00,800 --> 06:09:02,680 SKIN CELLS AND IT IS SPECIAL IN 8137 06:09:02,680 --> 06:09:06,000 THAT IT IS FAIRLY -- IT IS TUMOR 8138 06:09:06,000 --> 06:09:08,440 ASSOCIATED BUT REALLY MOSTLY 8139 06:09:08,440 --> 06:09:10,920 ABSENT IN NORMAL TISSUE. IN OUR 8140 06:09:10,920 --> 06:09:17,560 NC ISTORY HERE, OUR SCF TARGETS 8141 06:09:17,560 --> 06:09:19,960 PREDOMINANTLY AXON 3 AND 10 8142 06:09:19,960 --> 06:09:21,680 OCCURRING IN ISOFORM THAT YOU 8143 06:09:21,680 --> 06:09:24,360 SEE IN TUMORS THAT IS NOT 8144 06:09:24,360 --> 06:09:29,040 EXPRESSED AND NORMAL TISSUES AND 8145 06:09:29,040 --> 06:09:31,200 THEREFORE ARE MORE TUMOR 8146 06:09:31,200 --> 06:09:33,560 SPECIFIC AND HAVE BEEN EFFORTS 8147 06:09:33,560 --> 06:09:36,080 THAT LOOK AT NEW TUMOR ANTIGENS 8148 06:09:36,080 --> 06:09:38,680 AND ONE STORY HERE IS REALLY 8149 06:09:38,680 --> 06:09:41,160 PARADIGM SHIFTING PUBLISHED IN 8150 06:09:41,160 --> 06:09:43,200 NATURE LAST YEAR BY CHOC GROUP 8151 06:09:43,200 --> 06:09:46,120 WHERE THEY DEVELOPED A PEP TICK 8152 06:09:46,120 --> 06:09:48,960 CENTRIC CAR THAT, AGAIN IS 2B 8153 06:09:48,960 --> 06:09:51,560 PEPTIDE PRESENTED THROUGH HLA 8154 06:09:51,560 --> 06:09:53,920 AND IS A TRANSCRIPTION FACTOR 8155 06:09:53,920 --> 06:09:56,120 AND NEUROBLASTOMA THAT IS 8156 06:09:56,120 --> 06:09:58,720 OPENING A WHOLE NEW, YOU KNOW, 8157 06:09:58,720 --> 06:10:00,240 AREA FOR DEVELOPMENT BUT KNOWING 8158 06:10:00,240 --> 06:10:02,800 A LITTLE BIT ABOUT THE HISTORY 8159 06:10:02,800 --> 06:10:05,120 OF THE DEVELOPMENT AND IT WAS 8160 06:10:05,120 --> 06:10:07,400 DIFFICULT TO FIND THE KIND THAT 8161 06:10:07,400 --> 06:10:09,360 TOOK ALMOST A DECADE AND 8162 06:10:09,360 --> 06:10:12,480 CERTAINLY IS PARADIGM SHIFTING. 8163 06:10:12,480 --> 06:10:14,280 ANOTHER WAY THAT PEOPLE HAVE 8164 06:10:14,280 --> 06:10:17,120 ADDRESSED THIS ALSO IS, YOU 8165 06:10:17,120 --> 06:10:21,200 KNOW, TO COME UP WITH NEW 8166 06:10:21,200 --> 06:10:22,400 [INDISCERNIBLE] NOT TALKING 8167 06:10:22,400 --> 06:10:24,480 ABOUT MANIPULATING DIFFERENT 8168 06:10:24,480 --> 06:10:27,560 COMPONENTS OF CARS AND COMING UP 8169 06:10:27,560 --> 06:10:29,240 WITH GAINING STRATEGIES AND ONE 8170 06:10:29,240 --> 06:10:31,960 CAME OUT FROM THE LAB AT UCSF 8171 06:10:31,960 --> 06:10:34,760 THAT IS A RECEPTOR WHERE 8172 06:10:34,760 --> 06:10:37,840 BASICALLY THROUGH THAT SYNAPSE 8173 06:10:37,840 --> 06:10:40,520 RECEPTOR CELL SENDS FIRST 8174 06:10:40,520 --> 06:10:41,720 ANTIGEN AND INDUCES EXPRESSION 8175 06:10:41,720 --> 06:10:44,680 OF THE CAR AND WITH THAT CONCEPT 8176 06:10:44,680 --> 06:10:47,240 T-CELL SHOULD SPARE SINGLE 8177 06:10:47,240 --> 06:10:50,000 ANTIGEN AND KILL DUAL ANTIGEN 8178 06:10:50,000 --> 06:10:52,080 CELLS AND THEREFORE HAVE LESS 8179 06:10:52,080 --> 06:10:53,960 TOXICITY THAT HAS BEEN TRIED TO 8180 06:10:53,960 --> 06:10:56,640 -- THIS HAS BEEN INCORPORATED IN 8181 06:10:56,640 --> 06:10:59,200 SEVERAL DIFFERENT CONCEPTS FOR 8182 06:10:59,200 --> 06:11:02,600 EXAMPLE G2BH27 [INDISCERNIBLE] 8183 06:11:02,600 --> 06:11:07,400 FROM CHLA IF NOT MISTAKEN AND 8184 06:11:07,400 --> 06:11:09,600 [INDISCERNIBLE] CARS BUT HAVE 8185 06:11:09,600 --> 06:11:11,960 BEEN UNSUCCESSFUL IN UPSCALING 8186 06:11:11,960 --> 06:11:14,800 FOR CLINICAL USE OR USING IT IN 8187 06:11:14,800 --> 06:11:15,680 HUMAN CELLS. 8188 06:11:15,680 --> 06:11:17,480 AND WHEN WE TALK ABOUT 8189 06:11:17,480 --> 06:11:19,640 STRATEGIES TO OVERCOME IMMUNE 8190 06:11:19,640 --> 06:11:21,680 SUPPRESSIVE TME THERE ARE A 8191 06:11:21,680 --> 06:11:23,480 VARIETY OF APPROACHES THAT 8192 06:11:23,480 --> 06:11:26,360 PEOPLE HAVE UNDERTAKEN. I WOULD 8193 06:11:26,360 --> 06:11:28,960 SAY THAT ONE OF THE STRATEGIES 8194 06:11:28,960 --> 06:11:32,760 HAVE BEEN TO USE CYTOKINES TO 8195 06:11:32,760 --> 06:11:34,680 ARMOR CELLS WHETHER IT IS AS 8196 06:11:34,680 --> 06:11:36,400 TRUCKS WHERE CAR T-CELLS WILL 8197 06:11:36,400 --> 06:11:41,880 THEN COME TO THE TME AND SECRETE 8198 06:11:41,880 --> 06:11:46,040 CYTOKINES MODULATING TMC AND 8199 06:11:46,040 --> 06:11:47,680 ARMORED HAVING CYTOKINES 8200 06:11:47,680 --> 06:11:50,480 TETHERED TO THEIR SURFACE AND 8201 06:11:50,480 --> 06:11:52,240 STIMULATING EACH OTHER IN 8202 06:11:52,240 --> 06:11:54,880 AUTOKINE AND PAIRO CYANMANNER 8203 06:11:54,880 --> 06:11:57,840 AND MOST COMMON CYTOKINES USED 8204 06:11:57,840 --> 06:11:59,960 FOR THIS PURPOSE ARE FROM FA M 8205 06:11:59,960 --> 06:12:02,720 MLY OF CYTOKINES WE KNOW THEY 8206 06:12:02,720 --> 06:12:06,000 HAVE POSITIVE EFFECTS ON T-CELL 8207 06:12:06,000 --> 06:12:07,480 BIOLOGY AND K CELL BIOLOGY AND 8208 06:12:07,480 --> 06:12:09,640 SO ON AND SO FORTH AND IN THIS 8209 06:12:09,640 --> 06:12:12,040 CONTEXT IT IS IMPORTANT TO -- TO 8210 06:12:12,040 --> 06:12:14,360 CONSIDER AND TO THINK ABOUT THE 8211 06:12:14,360 --> 06:12:16,120 TOXICITIES THAT COULD BE 8212 06:12:16,120 --> 06:12:17,880 ASSOCIATED WITH THAT. SO, I 8213 06:12:17,880 --> 06:12:20,040 THINK THAT THE PUSH IN THE FIELD 8214 06:12:20,040 --> 06:12:23,960 NOW IS TO ALSO MOVE TOWARDS 8215 06:12:23,960 --> 06:12:26,360 CONDITIONALLY EXPRESSED CYTOKINE 8216 06:12:26,360 --> 06:12:30,400 SYSTEMS AND WE HEARD FROM 8217 06:12:30,400 --> 06:12:34,400 CLAUDIA ABOUT NFAT18 PRODUCT 8218 06:12:34,400 --> 06:12:35,800 THAT WILL OPEN IN GERMANY AND 8219 06:12:35,800 --> 06:12:37,920 ANOTHER WAY TO DO THAT IS USING 8220 06:12:37,920 --> 06:12:40,360 THAT APPROACH THAT I TALK ABOUT 8221 06:12:40,360 --> 06:12:42,280 BEFORE WITH IL2 THAT HAS BEEN 8222 06:12:42,280 --> 06:12:46,040 DONE AT UCSF AND IN PRECLINICAL 8223 06:12:46,040 --> 06:12:48,880 MODELS AND I THINK THAT REALLY 8224 06:12:48,880 --> 06:12:50,880 CAR T-CELLS HAVE LIMITED 8225 06:12:50,880 --> 06:12:52,560 ANTITUMOR ACTIVITY LOOKING AT 8226 06:12:52,560 --> 06:12:54,600 PREVIOUS TRIALS THAT HAVE BEEN 8227 06:12:54,600 --> 06:12:58,040 RECORDED AND IS IMPORTANT THAT 8228 06:12:58,040 --> 06:13:01,320 WE COME UP WITH NEW APPROACHES 8229 06:13:01,320 --> 06:13:03,680 TO OVERCOME UNIQUE CHALLENGES I 8230 06:13:03,680 --> 06:13:06,560 MENTIONED THAT NOT ONLY 8231 06:13:06,560 --> 06:13:07,240 INCORPORATE CREATIVE CAR DESIGN 8232 06:13:07,240 --> 06:13:09,480 NOT TALKING ABOUT ITERATIONS OF 8233 06:13:09,480 --> 06:13:12,800 CAR COMPONENTS AND GAINING NEW 8234 06:13:12,800 --> 06:13:16,160 STRATEGIES AND THEN ALSO LOOKING 8235 06:13:16,160 --> 06:13:18,200 AT FINE TUNING CAR FUNCTION AND 8236 06:13:18,200 --> 06:13:21,520 CHALLENGE RING PRECLINICAL 8237 06:13:21,520 --> 06:13:24,800 MODELS USING ORTHOGONAL 8238 06:13:24,800 --> 06:13:27,440 APPROACHES SUCH AS TRANSGENIC 8239 06:13:27,440 --> 06:13:29,320 CYTOKINES AND I HAVEN'T TOUCHED 8240 06:13:29,320 --> 06:13:31,920 UPON WHETHER OUR CURRENT 8241 06:13:31,920 --> 06:13:34,280 CONDITIONING REJIMMEN HAS TO BE 8242 06:13:34,280 --> 06:13:36,880 OPTIMIZED USING WHAT LUKEMIA 8243 06:13:36,880 --> 06:13:38,960 COLLEAGUES USED IN TRIALS AND 8244 06:13:38,960 --> 06:13:41,760 TRANSPLANTED IT INTO SOLID 8245 06:13:41,760 --> 06:13:43,080 TUMORS AND THERE IS CERTAINLY 8246 06:13:43,080 --> 06:13:46,120 ROOM WITH NEWER APPROACHES LIKE 8247 06:13:46,120 --> 06:13:47,800 TARGETED RADIO THERAPY FOR 8248 06:13:47,800 --> 06:13:54,680 EXAMPLE TO TARGET NOT ONLY 8249 06:13:54,680 --> 06:13:55,840 LYMPHOOCYTES IN THE SPACE BUT 8250 06:13:55,840 --> 06:14:00,280 [INDISCERNIBLE] ITSELF AND 8251 06:14:00,280 --> 06:14:02,280 LASTLY THIS CONCEPT CAME UP 8252 06:14:02,280 --> 06:14:04,480 ALREADY AND NOT JUST CELLULAR 8253 06:14:04,480 --> 06:14:06,520 WITH CELLULAR BUT SYNTHETIC 8254 06:14:06,520 --> 06:14:09,000 APPROACHES SUCH AS 8255 06:14:09,000 --> 06:14:10,160 IMMUNOCYTOKINE AND NEXT 8256 06:14:10,160 --> 06:14:12,720 GENERATION CYTOKINES THAT ARE 8257 06:14:12,720 --> 06:14:15,120 MODULATED JUST TO YOU KNOW 8258 06:14:15,120 --> 06:14:17,560 STIMULATE CERTAIN CELL 8259 06:14:17,560 --> 06:14:19,160 POPULATIONS OF LYMPHOOCYTES. 8260 06:14:19,160 --> 06:14:30,040 WITH THAT I END. THANK YOU. 8261 06:14:30,040 --> 06:15:23,120 >> [INDISCERNIBLE]. 8262 06:15:23,120 --> 06:15:25,640 >> YEAH. I THINK THIS IS AN 8263 06:15:25,640 --> 06:15:28,200 IMPORTANT POINT. MOST 8264 06:15:28,200 --> 06:15:29,680 PRECLINICAL CAR T STUDIES ARE 8265 06:15:29,680 --> 06:15:35,080 DONE IN HUMANIZED MODELS WHERE 8266 06:15:35,080 --> 06:15:38,600 WE HAVE ONLY T-CELLS AND PDXS 8267 06:15:38,600 --> 06:15:40,560 AND PUSH AND REASON FOR GOING 8268 06:15:40,560 --> 06:15:42,120 THERE IS BECAUSE WE USE A TUMOR 8269 06:15:42,120 --> 06:15:44,600 THAT IS CLOSE TO THE CLINIC. IF 8270 06:15:44,600 --> 06:15:48,120 YOU REALLY WANT TO MODEL THIS 8271 06:15:48,120 --> 06:15:51,760 AND STUDY IT YOU NEED RELIABLE 8272 06:15:51,760 --> 06:15:53,720 MODELS WHERE YOU HAVE ENTIRE 8273 06:15:53,720 --> 06:15:56,280 IMMUNE SYSTEM OR HUMANIZED 8274 06:15:56,280 --> 06:15:58,480 MODELS THAT ARE VERY CHALLENGING 8275 06:15:58,480 --> 06:16:03,120 AND BRINGING UP MR. G MICE 8276 06:16:03,120 --> 06:16:05,320 DEVELOPED AT YALE WHERE YOU 8277 06:16:05,320 --> 06:16:07,080 BREED THEM AND INJECT WHEN THEY 8278 06:16:07,080 --> 06:16:09,280 ARE LITTLE INTO THE LIVER AND 8279 06:16:09,280 --> 06:16:11,320 THEY GROW UP AND STILL NO 8280 06:16:11,320 --> 06:16:13,640 T-CELLS YOU DON'T IMPLANT A 8281 06:16:13,640 --> 06:16:15,440 THYMUS. THEY DON'T SURVIVE THAT 8282 06:16:15,440 --> 06:16:17,280 LONG BECAUSE OF ANEMIA. YOU 8283 06:16:17,280 --> 06:16:17,920 KNOW? 8284 06:16:17,920 --> 06:16:20,840 SO, I THINK THAT HUMANIZED MOUSE 8285 06:16:20,840 --> 06:16:23,560 WORLD STILL HAS WAYS TO GO TO 8286 06:16:23,560 --> 06:16:26,680 COME UP WITH LONG-LASTING 8287 06:16:26,680 --> 06:16:28,800 HUMANIZED MODELS AND BEST WE CAN 8288 06:16:28,800 --> 06:16:31,280 DO NOW IS [INDISCERNIBLE] AND I 8289 06:16:31,280 --> 06:16:33,160 THINK THAT TRANSPLANTABLE MODELS 8290 06:16:33,160 --> 06:16:36,560 IS WAY TO GO WHERE YOU CAN DO IT 8291 06:16:36,560 --> 06:16:38,320 ORTHOTOPICALLY FOR SOLID TUMORS 8292 06:16:38,320 --> 06:16:40,920 AND ENROLL THEM NOT ON ROLLING 8293 06:16:40,920 --> 06:16:43,600 BASIS. THAT IS LOGISTICALLY 8294 06:16:43,600 --> 06:16:47,040 VERY CHALLENGE RING AND TIME IT 8295 06:16:47,040 --> 06:16:49,440 AND TRY THAT. 8296 06:16:49,440 --> 06:16:51,760 >> I THINK ALL MODELS ARE 8297 06:16:51,760 --> 06:16:53,200 HORRIBLE AND WE HAVE TO DO 8298 06:16:53,200 --> 06:16:54,480 CLINICAL TRIALS AND THINK WE ARE 8299 06:16:54,480 --> 06:16:57,080 GOING TO DO AND WE TRY TO DO 8300 06:16:57,080 --> 06:16:59,040 STRONG CORRELATIVES IN TRIALS TO 8301 06:16:59,040 --> 06:17:02,480 SEE WHAT WE CAN LEARN AND TEST 8302 06:17:02,480 --> 06:17:03,480 HYPOTHESES. YOU CAN'T TEST 8303 06:17:03,480 --> 06:17:06,000 EVERYTHING IN A HUMAN OBVIOUSLY 8304 06:17:06,000 --> 06:17:09,840 AND AT A KEYSTONE RECENTLY AND 8305 06:17:09,840 --> 06:17:14,680 CRYSTAL GAVE KEYNOTE AND 8306 06:17:14,680 --> 06:17:19,560 MYELODEPLETION -- DALIA FROM FDC 8307 06:17:19,560 --> 06:17:22,720 CHILDREN'S GAVE A TALK IN MODEL 8308 06:17:22,720 --> 06:17:25,560 WHERE OPPOSITE IS TRUE AND LOSE 8309 06:17:25,560 --> 06:17:27,000 EFFECT OF CAR T-CELLS. 8310 06:17:27,000 --> 06:17:28,760 THERE IS ONLY ONE WAY 8311 06:17:28,760 --> 06:17:32,480 UNFORTUNATELY TO FIND OUT AND SO 8312 06:17:32,480 --> 06:17:34,160 I DON'T KNOW HOW TO DEAL WITH 8313 06:17:34,160 --> 06:17:36,680 THAT EXACTLY WE SAY AND I WRITE 8314 06:17:36,680 --> 06:17:38,400 IN GRANT AND ALTERNATIVE TO DO 8315 06:17:38,400 --> 06:17:40,800 IN A MODEL AND I WON'T DO IT AND 8316 06:17:40,800 --> 06:17:43,880 DON'T WANT TO SET ONE UP BUT NOT 8317 06:17:43,880 --> 06:17:48,600 SURE IF THEY REPRESENT HUMANS. 8318 06:17:48,600 --> 06:17:49,520 >> GOOD ANSWER. 8319 06:17:49,520 --> 06:17:50,760 >> NOT FOR-NIH. 8320 06:17:50,760 --> 06:17:51,320 >> [LAUGHING]. 8321 06:17:51,320 --> 06:17:53,880 >> I WAS GOING TO ASK A QUESTION 8322 06:17:53,880 --> 06:17:55,920 BUT NOW WOULD MUCH RATHER MAKE A 8323 06:17:55,920 --> 06:17:56,760 COMMENT. 8324 06:17:56,760 --> 06:17:58,400 SO, FIRST I COULDN'T AGREE MORE 8325 06:17:58,400 --> 06:18:01,040 AND I WOULD LIKE TO LET YOU ALL 8326 06:18:01,040 --> 06:18:02,360 KNOW THAT MAYBE SOME PEOPLE 8327 06:18:02,360 --> 06:18:05,360 DON'T KNOW. FIRST STUDY THAT 8328 06:18:05,360 --> 06:18:07,880 MALCOLM BRENNER DID WITH A 8329 06:18:07,880 --> 06:18:09,080 BLASTOMA WAS DONE WITHOUT 8330 06:18:09,080 --> 06:18:11,040 KILLING A SINGLE MOUSE AND WENT 8331 06:18:11,040 --> 06:18:13,080 FROM IN VITRO DIRECTED TO 8332 06:18:13,080 --> 06:18:14,720 CLINICAL TRIAL AND WISH WE COULD 8333 06:18:14,720 --> 06:18:15,840 DO IT AGAIN. 8334 06:18:15,840 --> 06:18:18,040 >> WHICH FDA PERSON DID YOU 8335 06:18:18,040 --> 06:18:22,880 KIDNAP? WHAT DID YOU DO? 8336 06:18:22,880 --> 06:18:25,320 >> I DON'T KNOW. WE WENT FOR IT 8337 06:18:25,320 --> 06:18:28,080 AND COMPLETELY AGREED AT THAT 8338 06:18:28,080 --> 06:18:31,320 TIME AT HOUSTON AND AT THAT TIME 8339 06:18:31,320 --> 06:18:33,800 THERE WAS NO MICE KILLED WE SAID 8340 06:18:33,800 --> 06:18:35,120 THEY DON'T REPRESENT THE 8341 06:18:35,120 --> 06:18:37,680 SITUATION IN HUMANS AND IS HOW I 8342 06:18:37,680 --> 06:18:40,600 WAS RAISED. 8343 06:18:40,600 --> 06:18:41,640 >> YEAH. 8344 06:18:41,640 --> 06:18:44,280 >> JUST LOVE YOU REMIND US OF 8345 06:18:44,280 --> 06:18:45,640 THAT AGAIN. 8346 06:18:45,640 --> 06:18:47,480 CAN I ASK MY QUESTION STILL? 8347 06:18:47,480 --> 06:18:49,200 WE WANT TO SOLVE THAT 8348 06:18:49,200 --> 06:18:50,160 REQUIREMENT PROBABLY. 8349 06:18:50,160 --> 06:18:53,240 WHY DO WE GET AWAY WITH 8350 06:18:53,240 --> 06:18:54,720 TARGETING GD2 SO EFFECTIVELY? 8351 06:18:54,720 --> 06:18:57,200 DO YOU THINK IT IS A THRESHOLD 8352 06:18:57,200 --> 06:18:58,520 ISSUE ALONE? 8353 06:18:58,520 --> 06:19:01,920 ANYTHING THAT PROTECTS GD2 8354 06:19:01,920 --> 06:19:03,120 EXPRESSING BRAIN CELLS ANYTHING 8355 06:19:03,120 --> 06:19:04,600 ON TOP OF THRESHOLD? 8356 06:19:04,600 --> 06:19:05,520 WHAT DO YOU THINK? 8357 06:19:05,520 --> 06:19:08,600 YOU PROBABLY DON'T KNOW ABOUT. 8358 06:19:08,600 --> 06:19:09,720 >> YEAH. GREAT QUESTION. 8359 06:19:09,720 --> 06:19:12,440 FIRST, IF YOU LOOK ON HUMAN OR 8360 06:19:12,440 --> 06:19:16,000 NORMAL BRAIN VERSUS DIPG BY IHC 8361 06:19:16,000 --> 06:19:19,440 THERE IS 100 FOLD INCREASE 8362 06:19:19,440 --> 06:19:21,560 INTENSITY FOR GD2 STAINING AND 8363 06:19:21,560 --> 06:19:23,480 PART HAS TO BE THRESHOLD AND 8364 06:19:23,480 --> 06:19:26,520 BELIEVE AT ONE POINT WE MAKE 8365 06:19:26,520 --> 06:19:28,760 EFFICIENT ENOUGH GD2 CAR NOT 8366 06:19:28,760 --> 06:19:30,440 EXHAUSTED AND POTENT ENOUGH TO 8367 06:19:30,440 --> 06:19:32,600 RECOGNIZE LOW LEVELS OF GD2 AND 8368 06:19:32,600 --> 06:19:35,320 LOW LEVELS OF TOX TIS I AND NOW 8369 06:19:35,320 --> 06:19:37,600 SEEM TO BE IN THERAPEUTIC WINDOW 8370 06:19:37,600 --> 06:19:41,200 AND THAT SAID NOT SURE IT IS 8371 06:19:41,200 --> 06:19:41,400 TRUE. 8372 06:19:41,400 --> 06:19:45,560 YOU KNOW, GD2 ANTIBODY MEDIATED 8373 06:19:45,560 --> 06:19:46,880 PAIN IS STILL POORLY UNDERSTOOD 8374 06:19:46,880 --> 06:19:49,400 AND WE GET NONE IN A MOUSE 8375 06:19:49,400 --> 06:19:52,680 DESPITE FACT THAT GD2 IS 8376 06:19:52,680 --> 06:19:55,720 EXPRESSED IN MOUSE AND DON'T GET 8377 06:19:55,720 --> 06:19:59,640 IT CELLS AND HAPPENING 8378 06:19:59,640 --> 06:20:02,520 CROSS-LINKING OF GD2 ANTIBODY 8379 06:20:02,520 --> 06:20:04,360 POTENTIAL ON FIBERS DOESN'T SEEM 8380 06:20:04,360 --> 06:20:06,920 TO BE IMMUNE ATTACK ON CELLS 8381 06:20:06,920 --> 06:20:10,120 WHEN DRAWING ANTIBODIES, 8382 06:20:10,120 --> 06:20:12,320 PATIENTS ARE FINE. I DON'T 8383 06:20:12,320 --> 06:20:12,520 KNOW. 8384 06:20:12,520 --> 06:20:15,040 >> ARE WE ASKING OUT OF 8385 06:20:15,040 --> 06:20:18,840 CURIOSITY? I'M AFRAID OF SEEING 8386 06:20:18,840 --> 06:20:20,400 NEUROTOXICITY ONE DAY WHEN WE 8387 06:20:20,400 --> 06:20:22,120 GET THEM SUFFICIENTLY EFFECTIVE 8388 06:20:22,120 --> 06:20:25,840 TO REALLY CURE THE DISEASE. 8389 06:20:25,840 --> 06:20:26,280 >> YEAH. 8390 06:20:26,280 --> 06:20:27,040 >> SAME CONCERNS. 8391 06:20:27,040 --> 06:20:28,680 >> I THINK IT IS AMAZING. 8392 06:20:28,680 --> 06:20:30,160 >> AND IF IT IS BRAVE AND JUST 8393 06:20:30,160 --> 06:20:32,360 DO IT AND I WOULDN'T HAVE BEEN. 8394 06:20:32,360 --> 06:20:35,680 >> YOU DID IT WITHOUT EVER 8395 06:20:35,680 --> 06:20:36,880 TESTING IN A MOUSE. 8396 06:20:36,880 --> 06:20:40,560 >> NOT IN CNS COUNTER. YEAH. 8397 06:20:40,560 --> 06:20:44,600 >> PERIPHERAL NEUROPATHY. 8398 06:20:44,600 --> 06:20:49,560 >> JUMPING IN AT ONE POINT 8399 06:20:49,560 --> 06:20:51,840 SARAH RICHMOND'S PAPER SHOWED 8400 06:20:51,840 --> 06:20:53,840 CLEARLY WITH MUCH BETTER BINDER 8401 06:20:53,840 --> 06:20:56,680 COMPLETE NEUROTOXICITY AND ALL 8402 06:20:56,680 --> 06:20:57,840 YOUR MICE ARE DEAD. 8403 06:20:57,840 --> 06:21:00,320 >> CONTROVERSIAL FINDING I WOULD 8404 06:21:00,320 --> 06:21:00,520 SAY. 8405 06:21:00,520 --> 06:21:01,880 >> IT IS CONTROVERSIAL. 8406 06:21:01,880 --> 06:21:04,120 >> YOU KNOW, WE HAVE MADE THAT 8407 06:21:04,120 --> 06:21:04,760 BINDER AND TRIED. 8408 06:21:04,760 --> 06:21:08,240 WE HAVE USED IT IN MANY, MANY 8409 06:21:08,240 --> 06:21:10,640 MODELS AND KRYSTAL USES IT AS 8410 06:21:10,640 --> 06:21:16,360 MODEL OF EXHAUSTION AND LOTS OF 8411 06:21:16,360 --> 06:21:19,120 POE 10CY ENHANCEMENTS AND SITES 8412 06:21:19,120 --> 06:21:22,840 ARE SIMILAR AND BRAIN EXPRESSED 8413 06:21:22,840 --> 06:21:25,240 HIGHER LEVELS OF COMPLEX GANG 8414 06:21:25,240 --> 06:21:27,360 LEEE CITES AND CROSS-REACTIVITY 8415 06:21:27,360 --> 06:21:28,680 WITH THOSE AND WOULDN'T CHANGE 8416 06:21:28,680 --> 06:21:30,080 WHY WE GET IT OR DON'T SEE IT. 8417 06:21:30,080 --> 06:21:32,920 >> THAT IS INTERESTING. SHOWING 8418 06:21:32,920 --> 06:21:33,640 THE SAME THING. 8419 06:21:33,640 --> 06:21:36,760 SO, I GUESS THERE IS A NICE 8420 06:21:36,760 --> 06:21:37,640 LITTLE CONTEXT. 8421 06:21:37,640 --> 06:21:41,880 >> DAVID AT MSK SEES IT IT MUST 8422 06:21:41,880 --> 06:21:43,360 BE NORTHEAST THING VERSUS 8423 06:21:43,360 --> 06:21:44,360 CALIFORNIA I DON'T KNOW. 8424 06:21:44,360 --> 06:21:46,800 >> THANKS FOR ROBUST DISCUSSION. 8425 06:21:46,800 --> 06:21:48,600 BEING EXITED OFF STAGE AND ONE 8426 06:21:48,600 --> 06:21:52,800 MORE ROUND OF APPLAUSE FOR 8427 06:21:52,800 --> 06:21:53,840 SPEAKERS, PLEASE. 8428 06:21:53,840 --> 06:21:55,920 >> [APPLAUSE]. 8429 06:21:55,920 --> 06:22:02,040 >> FOR CONCLUDING SESSION 8430 06:22:02,040 --> 06:22:04,400 STARTING WITH DR. KRYSTAL MCHLTD 8431 06:22:04,400 --> 06:22:08,800 WHO IS A PROFESSOR OF PEDIATRICS 8432 06:22:08,800 --> 06:22:11,640 IN MEDICINE AT STAN FORWARD AND 8433 06:22:11,640 --> 06:22:16,400 FOUNDING DIRECTOR AT CANCER CELL 8434 06:22:16,400 --> 06:22:20,360 INSTITUTE AND DIRECTOR OF PARKER 8435 06:22:20,360 --> 06:22:23,760 INSTITUTE AT STANFORD WITH 8436 06:22:23,760 --> 06:22:28,040 NUMEROUS ACCOLADES IN 8437 06:22:28,040 --> 06:22:33,080 GROUNDBREAKING WORK. 8438 06:22:33,080 --> 06:22:36,680 SHE ENDED TERM AS CHIEF OF POB 8439 06:22:36,680 --> 06:22:39,160 AND IMMUNOLOGY SECTIONS AND 8440 06:22:39,160 --> 06:22:40,480 COMING TO STANFORD I RECOGNIZE 8441 06:22:40,480 --> 06:22:46,120 HER TO BE A TRANSLATIONAL AND 8442 06:22:46,120 --> 06:22:47,320 REVERSE TRANSLATIONAL MASTERMIND 8443 06:22:47,320 --> 06:22:51,480 IN PEDIATRICS ROBBY PRESENTED 8444 06:22:51,480 --> 06:22:53,920 GD2 TRIAL AND I WENT ON 8445 06:22:53,920 --> 06:22:55,160 MATERNITY LEAVE. BEFORE GOING 8446 06:22:55,160 --> 06:22:57,360 ON LEAVE THERE WAS NO BRAIN 8447 06:22:57,360 --> 06:22:59,320 TUMOR TRIAL AND AFTER COMING ON 8448 06:22:59,320 --> 06:23:01,520 LEAVE THERE WAS A BRAIN TUMOR 8449 06:23:01,520 --> 06:23:05,200 TRIAL SHE BUILDS INFRASTRUCTURE 8450 06:23:05,200 --> 06:23:10,320 AS A REGULATORY EXPERTS UNMASKS 8451 06:23:10,320 --> 06:23:16,120 THERAPY AND CRYSTAL THANK YOU. 8452 06:23:16,120 --> 06:23:18,440 >> GOOD GOOD AFTERNOON. SORRY 8453 06:23:18,440 --> 06:23:20,720 NOT ABLE TO BE THERE IN PERSON. 8454 06:23:20,720 --> 06:23:24,880 IT IS HARD TO PROVIDE CLOSING 8455 06:23:24,880 --> 06:23:27,920 REMARKS OR MEETING THAT YOU WERE 8456 06:23:27,920 --> 06:23:33,200 NOT YET SEEN AND HOPE THEY ALIGN 8457 06:23:33,200 --> 06:23:35,440 IN SOME WAYS WITH ISSUES RAISE 8458 06:23:35,440 --> 06:23:39,160 THE EARLIER TODAY AND CAN 8459 06:23:39,160 --> 06:23:40,440 PROVIDE SOME FOOD FOR THOUGHT 8460 06:23:40,440 --> 06:23:42,800 AND I ENTITLED THIS DELIVERING 8461 06:23:42,800 --> 06:23:45,320 ON PROMISE OF CAR T-CELLS FOR 8462 06:23:45,320 --> 06:23:47,080 CHILDREN'S CANCERS AND 8463 06:23:47,080 --> 06:23:50,000 DISCLOSURES ARE SHOWN THERE. 8464 06:23:50,000 --> 06:23:52,440 SO, TO LEVEL SET IN FEBRUARY 8465 06:23:52,440 --> 06:23:54,520 2023, I THINK THERE IS EVERY 8466 06:23:54,520 --> 06:23:56,640 REASON TO BE OPTIMISTIC ABOUT 8467 06:23:56,640 --> 06:23:59,880 THE PROGRESS MADE AND USE OF CAR 8468 06:23:59,880 --> 06:24:01,400 T-CELLS WITH TREATMENT OF CANCER 8469 06:24:01,400 --> 06:24:03,880 AND TO BELIEVE THAT THIS IS 8470 06:24:03,880 --> 06:24:06,360 STILL THE TIP OF THE ICEBERG. 8471 06:24:06,360 --> 06:24:10,160 WE HAVE 12 APPROVALS FOR 6 8472 06:24:10,160 --> 06:24:13,400 PRODUCTS AND THREE TARGETS 8473 06:24:13,400 --> 06:24:14,920 SPANNING 5 COMPANIES. 8474 06:24:14,920 --> 06:24:19,400 ONE, YAY, IS FOR PEDIATRIC 8475 06:24:19,400 --> 06:24:20,080 INDICATION. I THINK THAT EVEN 8476 06:24:20,080 --> 06:24:22,360 THOSE OF US WHO ARE ALREADY 8477 06:24:22,360 --> 06:24:24,880 BELIEVERS IN 2010 WHEN FIRST 8478 06:24:24,880 --> 06:24:27,640 PATIENT WAS TREATED FOR LYMPHOMA 8479 06:24:27,640 --> 06:24:29,800 AT NIH AND KNEW IT WOULD BE 8480 06:24:29,800 --> 06:24:32,920 SOMETHING REALLY EXCITING, CAR 8481 06:24:32,920 --> 06:24:35,400 T-CELLS ABOUT FORM OR OUTSTRIP 8482 06:24:35,400 --> 06:24:37,280 EXPECTATIONS OF EVEN MANY OF 8483 06:24:37,280 --> 06:24:41,440 THOSE OF US WHO ARE ALREADY 8484 06:24:41,440 --> 06:24:42,080 BELIEVERS. 8485 06:24:42,080 --> 06:24:43,720 IF WE WANT TO LOOK BACK AT HOW 8486 06:24:43,720 --> 06:24:45,680 WE GOT HERE, IT IS IMPORTANT TO 8487 06:24:45,680 --> 06:24:47,280 UNDERSTAND THAT WHILE IT LOOKS 8488 06:24:47,280 --> 06:24:50,680 LIKE SOME OF THE STUFF HAPPENED 8489 06:24:50,680 --> 06:24:53,680 OVERNIGHT, IT DIDN'T. 8490 06:24:53,680 --> 06:24:54,640 ESSENTIALLY, ANY NEW THERAPY 8491 06:24:54,640 --> 06:24:58,720 THAT HAS VALUE IN THE CLINIC, IF 8492 06:24:58,720 --> 06:25:01,560 YOU GO BACK AND LOOK, IT MOST 8493 06:25:01,560 --> 06:25:05,360 LIKELY HAS EARLY DEVELOPMENTAL 8494 06:25:05,360 --> 06:25:08,280 ROOTS 2 OR 3 DECADES BEFORE 8495 06:25:08,280 --> 06:25:11,000 CLINICAL SIGNAL IS SEEN AND CAR 8496 06:25:11,000 --> 06:25:12,680 T-CELLS ARE NO EXCEPTION THERE 8497 06:25:12,680 --> 06:25:14,240 AND RECENT REVIEW COMING OUT 8498 06:25:14,240 --> 06:25:17,240 THIS WEEK IN NATURE, WE TRIED TO 8499 06:25:17,240 --> 06:25:18,600 SUMMARIZE AT A VERY HIGH LEVEL 8500 06:25:18,600 --> 06:25:20,280 HOW WE GOT TO WHERE WE ARE 8501 06:25:20,280 --> 06:25:20,520 TODAY. 8502 06:25:20,520 --> 06:25:26,400 IT REALLY STARTED IN 1989 WITH 8503 06:25:26,400 --> 06:25:27,880 AMAZING CREATIVE IDEA FROM 8504 06:25:27,880 --> 06:25:28,720 [INDISCERNIBLE] THAT YOU COULD 8505 06:25:28,720 --> 06:25:30,920 GET OUT FROM UNDER THE IMAGE 8506 06:25:30,920 --> 06:25:33,720 RESTRICTION OF A T-CELL WITH 8507 06:25:33,720 --> 06:25:37,320 SO-CALLED T BODY OR RECEPTOR 8508 06:25:37,320 --> 06:25:41,200 THAT LINKS UP T-CELL ACTIVATION 8509 06:25:41,200 --> 06:25:43,000 MACHINERY WITH BINDER IT THAT IS 8510 06:25:43,000 --> 06:25:46,520 NOT MAC RESTRICTED AND REMAINS A 8511 06:25:46,520 --> 06:25:48,000 CONCEPT THAT IS NOT QUITE 8512 06:25:48,000 --> 06:25:50,200 ACCEPTED FOR A FEW YEARS AND THE 8513 06:25:50,200 --> 06:25:53,080 FIRST ITERATION WAS PRETTY CRUDE 8514 06:25:53,080 --> 06:25:56,720 AND NOT PRETTY WEAK. 8515 06:25:56,720 --> 06:26:00,080 AFTER 5 OR 6 YEARS, YOU KNOW, 8516 06:26:00,080 --> 06:26:02,520 CONCEPT WAS APPROVED AND 8517 06:26:02,520 --> 06:26:03,960 THERAPEUTIC WAS NOWHERE NEAR 8518 06:26:03,960 --> 06:26:06,240 READY FOR CLINICAL TESTING THAT 8519 06:26:06,240 --> 06:26:09,680 REQUIRED ANOTHER DECADE OR SO OF 8520 06:26:09,680 --> 06:26:12,160 PROTOTYPE ITERATION. 8521 06:26:12,160 --> 06:26:15,000 ALONGSIDE JUST GENERAL 8522 06:26:15,000 --> 06:26:17,920 UNDERSTANDING OF HOW YOU EXPAND 8523 06:26:17,920 --> 06:26:21,840 T-CELLS EX-VIVO. 8524 06:26:21,840 --> 06:26:23,080 WHICH COSTIMULATORY DOMAINS ARE 8525 06:26:23,080 --> 06:26:25,800 USEFUL AND IDEA THAT YOU HAVE TO 8526 06:26:25,800 --> 06:26:28,480 INCLUDE A COSTIMULATORY DOMAIN 8527 06:26:28,480 --> 06:26:30,960 AND LEARN TO PREPARE HOST TO 8528 06:26:30,960 --> 06:26:33,680 RECEIVE T-CELL THERAPIES. 8529 06:26:33,680 --> 06:26:35,720 IT WASN'T REALLY UNTIL AROUND 8530 06:26:35,720 --> 06:26:38,320 2010 THAT WE SAW REAL AND TRUE 8531 06:26:38,320 --> 06:26:40,080 EVIDENCE OF CLINICAL PROOF OF 8532 06:26:40,080 --> 06:26:40,360 CONCEPT. 8533 06:26:40,360 --> 06:26:43,760 AND I THINK THAT THE REAL 8534 06:26:43,760 --> 06:26:46,120 TIPPING POINT ARGUABLY HAPPENED 8535 06:26:46,120 --> 06:26:50,960 IN 2012 WHEN BIOPHARMADECIDED TO 8536 06:26:50,960 --> 06:26:53,160 INVEST IN CAR T-CELL THERAPIES 8537 06:26:53,160 --> 06:26:56,640 AND UP TO THAT TIME DOGMA HAD 8538 06:26:56,640 --> 06:27:00,680 BEEN YOU COULDN'T COMMERCIALIZE 8539 06:27:00,680 --> 06:27:02,880 IN THERAPY. IT WOULD BE 8540 06:27:02,880 --> 06:27:05,040 IMPOSSIBLE TO DO AND FAST 8541 06:27:05,040 --> 06:27:09,880 FORWARD WITH COMMERCIALLY 8542 06:27:09,880 --> 06:27:10,560 SUPPORTED APPROVED CELL 8543 06:27:10,560 --> 06:27:12,160 THERAPIES AND IT SEEMS TO BE 8544 06:27:12,160 --> 06:27:13,880 EVER INCREASING AND IF YOU LOOK 8545 06:27:13,880 --> 06:27:17,080 AT PHASES, WE HAD A CONCEPT 8546 06:27:17,080 --> 06:27:19,000 PHASE OR PROTO TYPE ITERATION 8547 06:27:19,000 --> 06:27:20,960 PHASE AND WE HAD PHASE OF 8548 06:27:20,960 --> 06:27:23,800 CLINICAL PROOF OF CONCEPT AND 8549 06:27:23,800 --> 06:27:26,240 ARE NOW DEEP INTO THE 8550 06:27:26,240 --> 06:27:28,920 COMMERCIALIZATION PHASE. 8551 06:27:28,920 --> 06:27:31,560 AND TO PROVIDE MORE BASIS FOR 8552 06:27:31,560 --> 06:27:35,440 THAT NOTION. IF YOU LOOK AT THE 8553 06:27:35,440 --> 06:27:37,560 AMOUNT OF INVESTMENT HAPPENING 8554 06:27:37,560 --> 06:27:40,040 IN THE PRIVATE SECTOR IN THE 8555 06:27:40,040 --> 06:27:41,960 FIELD OF CELL AND GENE THERAPY, 8556 06:27:41,960 --> 06:27:45,280 IT IS JUST TRULY MIND BOGGLING. 8557 06:27:45,280 --> 06:27:48,000 THESE ARE A BIT OUTDATED AND ARE 8558 06:27:48,000 --> 06:27:50,080 DRAWN FROM 2021 REPORTS. 8559 06:27:50,080 --> 06:27:52,200 THERE HAS BEEN A DOWNTURN IN THE 8560 06:27:52,200 --> 06:27:55,080 MARKET SINCE THAT TIME. 8561 06:27:55,080 --> 06:27:56,600 NONETHELESS, IF YOU LOOK IN 8562 06:27:56,600 --> 06:28:02,440 AUGUST OF 2021, THERE WAS $14 8563 06:28:02,440 --> 06:28:02,960 BILLION. 8564 06:28:02,960 --> 06:28:07,720 14 BRS DLL INVESTED IN CELL AND 8565 06:28:07,720 --> 06:28:09,760 GENE REGENERATIVE THERAPIES AND 8566 06:28:09,760 --> 06:28:13,080 5 MILLION INVESTED BY VENTURE 8567 06:28:13,080 --> 06:28:14,400 CAPITALISTS INTO SMALL EARLY 8568 06:28:14,400 --> 06:28:16,920 STAGE PRIVATE STAGE BIOTECH AND 8569 06:28:16,920 --> 06:28:18,440 IS AMOUNT OF MONEY AROUND SAME 8570 06:28:18,440 --> 06:28:20,080 TIME AND IF YOU SAY AROUND HOW 8571 06:28:20,080 --> 06:28:21,600 MANY COMPANIES ARE THERE? I 8572 06:28:21,600 --> 06:28:23,240 DON'T KNOW WHAT ANSWER IS TODAY. 8573 06:28:23,240 --> 06:28:27,560 IN 2019 ACCORDING TO THIS MARKET 8574 06:28:27,560 --> 06:28:30,480 WATCH THERE IS 100 CELL AND GENE 8575 06:28:30,480 --> 06:28:32,800 THERAPY COMPANIES WORLDWIDE. 8576 06:28:32,800 --> 06:28:36,040 END OF 2020 IT INCREASED TO OVER 8577 06:28:36,040 --> 06:28:36,560 1,000. 8578 06:28:36,560 --> 06:28:38,520 THAT IS REMARKABLE GROWTH AND AT 8579 06:28:38,520 --> 06:28:41,560 THAT TIME MORE THAN 500 WERE 8580 06:28:41,560 --> 06:28:43,680 US-BASED COMPANIES AND IF YOU, 8581 06:28:43,680 --> 06:28:46,160 YOU KNOW, YOU LOOK AT YEAR 2022 8582 06:28:46,160 --> 06:28:49,360 TODAY WAS TRYING TO GET MORE 8583 06:28:49,360 --> 06:28:51,520 UPDATED NUMBERS ON AMOUNT OF 8584 06:28:51,520 --> 06:28:52,520 INVESTMENT, CURRENT ESTIMATE IS 8585 06:28:52,520 --> 06:28:55,160 THAT THE MARKET IS ABOUT $8.5 8586 06:28:55,160 --> 06:28:58,440 BILLION MARKET IN 2022. IT WILL 8587 06:28:58,440 --> 06:29:00,960 GROW AT AN ASTONISHING ANNUAL 8588 06:29:00,960 --> 06:29:05,000 GROWTH RATE OF 25% PER YEAR AND 8589 06:29:05,000 --> 06:29:06,440 ESTIMATED TO BE AROUND 20 8590 06:29:06,440 --> 06:29:09,360 BILLION BY 2026. REMARKABLE 8591 06:29:09,360 --> 06:29:11,240 GROWTH RATE. IN FACT TAKING 8592 06:29:11,240 --> 06:29:14,000 DEEP DIVE INTO THIS YOU CAN BUY 8593 06:29:14,000 --> 06:29:16,360 A GLOBAL MARKET REPORT AND 250 8594 06:29:16,360 --> 06:29:19,360 PAGE BOOK LOOKING AT PROJECTED 8595 06:29:19,360 --> 06:29:21,680 GROWTH IN THE SPACE. THIS BOOK 8596 06:29:21,680 --> 06:29:25,680 WILL SET YOU BACK ONLY $5,000. 8597 06:29:25,680 --> 06:29:27,920 TO JUST SHOW YOU HOW INTERESTED 8598 06:29:27,920 --> 06:29:30,600 THE PRIVATE SECTOR IS IN 8599 06:29:30,600 --> 06:29:32,520 UNDERSTANDING HOW THEY CAN GET 8600 06:29:32,520 --> 06:29:34,880 INVOLVED IN THIS DRAMATIC GROWTH 8601 06:29:34,880 --> 06:29:35,280 FIELD. 8602 06:29:35,280 --> 06:29:37,160 IT IS NOT JUST THE COMMERCIAL 8603 06:29:37,160 --> 06:29:40,440 SPACE THAT IS BREEDING THE 8604 06:29:40,440 --> 06:29:41,000 ENTHUSIASM. 8605 06:29:41,000 --> 06:29:43,720 CLEARLY THERE HAS BEEN DRAMATIC 8606 06:29:43,720 --> 06:29:47,520 PROGRESS IN ARENA OF SYNTHETIC 8607 06:29:47,520 --> 06:29:49,760 BIOLOGY AND CREATING NEWER AND 8608 06:29:49,760 --> 06:29:51,720 BETTER MORE EFFECTIVE RECEPTORS 8609 06:29:51,720 --> 06:29:55,600 FROM ORIGINAL PROTOTYPES THAT WE 8610 06:29:55,600 --> 06:29:58,120 ALL KNOW AND LOVE. 8611 06:29:58,120 --> 06:30:00,520 AND THIS IS FROM RECENT REVIEWS 8612 06:30:00,520 --> 06:30:02,360 SHOWING JUST, YOU KNOW, HOW MUCH 8613 06:30:02,360 --> 06:30:06,400 WE HAVE LEARNED. WE KNOW A LOT 8614 06:30:06,400 --> 06:30:10,480 ABOUT SINGLE CHAIN OF FEE PLAYS 8615 06:30:10,480 --> 06:30:13,560 AND WHAT ROLE HINGE AND SPACE 8616 06:30:13,560 --> 06:30:15,480 AND TRANSMEMBRANE DOMAINS AND 8617 06:30:15,480 --> 06:30:17,600 COSTIMULATION AND SIGNALING 8618 06:30:17,600 --> 06:30:20,120 THROUGH MODULATING CD3 AND EVERY 8619 06:30:20,120 --> 06:30:22,120 PART OF PROTOTYPE RECEPTOR CAN 8620 06:30:22,120 --> 06:30:25,000 BE ENGINEERED IN ORDER TO MAKE 8621 06:30:25,000 --> 06:30:27,360 THE CELL BEHAVE IN A WAY THAT IS 8622 06:30:27,360 --> 06:30:30,320 MORE LIKELY TO BENEFIT YOUR 8623 06:30:30,320 --> 06:30:30,800 PATIENT. 8624 06:30:30,800 --> 06:30:34,120 AND BEYOND THAT, WE ALSO 8625 06:30:34,120 --> 06:30:36,480 UNDERSTAND THAT THIS PROTOTYPE 8626 06:30:36,480 --> 06:30:39,360 CAR T-CELL AND, AGAIN, WE ARE 8627 06:30:39,360 --> 06:30:40,880 COMFORTABLE WITH TODAY IS LIKELY 8628 06:30:40,880 --> 06:30:44,200 TO BE OUTDATED IN NOT TOO 8629 06:30:44,200 --> 06:30:47,800 DISTANT FUTURE BETWEEN CREATING 8630 06:30:47,800 --> 06:30:48,880 MULTISPECIFICITY CARS AND IF 8631 06:30:48,880 --> 06:30:51,640 THEN GATES WHERE YOU HAVE TWO 8632 06:30:51,640 --> 06:30:54,320 SIGNAL LOGIC GATE AND TRUE END 8633 06:30:54,320 --> 06:30:56,400 GATE AND NEW LINK CAR COMING OUT 8634 06:30:56,400 --> 06:31:01,040 OF ROBBY'S LAB AND ALLOWING YOU 8635 06:31:01,040 --> 06:31:02,440 TO REQUIRE RECOGNITION OF TWO 8636 06:31:02,440 --> 06:31:06,280 IDS ALLOWING CELL TO FIRE AND 8637 06:31:06,280 --> 06:31:08,320 ADAPTOR AND REGULATABLE CARS AND 8638 06:31:08,320 --> 06:31:10,760 ONE CALLED SNIP CAR CAME OUT OF 8639 06:31:10,760 --> 06:31:13,520 LAB AND DRUG REGULATED WITH 8640 06:31:13,520 --> 06:31:16,240 PROTEASE SYSTEM ALLOWING TO USE 8641 06:31:16,240 --> 06:31:20,360 A SMALL MOLECULE FDA APPROVED 8642 06:31:20,360 --> 06:31:24,080 AND TO REGULATE CAR WE HAVE CARS 8643 06:31:24,080 --> 06:31:26,280 CREATED TO GO OUT UNDERNEATH 8644 06:31:26,280 --> 06:31:29,080 RADAR OF HUMAN SYSTEM 8645 06:31:29,080 --> 06:31:31,520 POTENTIALLY ALLOWING CARS TO BE 8646 06:31:31,520 --> 06:31:34,880 DELIVER AND PERHAPS PERSIST AND 8647 06:31:34,880 --> 06:31:37,640 IS IMMENSE AMOUNT OF 8648 06:31:37,640 --> 06:31:38,240 TRANSCRIPTIONAL PROGRAMMING 8649 06:31:38,240 --> 06:31:40,120 UNDERWAY AND ENTIRELY NEW WAYS 8650 06:31:40,120 --> 06:31:42,000 THINKING ABOUT MAKING SYNTHETIC 8651 06:31:42,000 --> 06:31:46,200 IMMUNE RECEPTORS AND MANY LOOK 8652 06:31:46,200 --> 06:31:51,000 LIKE ENDOGENOUS TC RECEPTOR AND 8653 06:31:51,000 --> 06:31:54,640 HARNESS BENEFITS OF THEM AND 8654 06:31:54,640 --> 06:31:57,560 ANTIGEN DENSITY AND LESS 8655 06:31:57,560 --> 06:31:58,840 SUSCEPTIBILITY TO EXHAUSTION AND 8656 06:31:58,840 --> 06:32:01,200 SIGNAL 3 IS AREA WHERE THERE IS 8657 06:32:01,200 --> 06:32:03,640 IMMENSE WORK TRYING TO DELIVER 8658 06:32:03,640 --> 06:32:05,720 CYTOKINE SIGNAL THAT IS IN A WAY 8659 06:32:05,720 --> 06:32:08,880 BOTH EFFECTIVE AND SAFE AND ONE 8660 06:32:08,880 --> 06:32:12,120 COULD ARGUE STOP CALLING 8661 06:32:12,120 --> 06:32:14,320 CHIMERIC ANTIJ YEN RECEPTORS 8662 06:32:14,320 --> 06:32:18,200 CALLING THEM -- BECAUSE OF THE 8663 06:32:18,200 --> 06:32:22,160 GREAT VARIABILITY IN THE 8664 06:32:22,160 --> 06:32:22,400 DESIGNS. 8665 06:32:22,400 --> 06:32:24,000 BEYOND DIFFERENT PLATFORMS ARE 8666 06:32:24,000 --> 06:32:25,880 INCREASING ARRAY OF ENHANCEMENTS 8667 06:32:25,880 --> 06:32:28,800 BY WHICH YOU CAN MODIFY BIOLOGY 8668 06:32:28,800 --> 06:32:30,720 OF MOSTLY T-CELLS BUT MANY OF 8669 06:32:30,720 --> 06:32:32,640 THE ENHANCEMENTS COULD BE USED 8670 06:32:32,640 --> 06:32:36,520 FOR IN K CELLS OR MACRO PHAGES 8671 06:32:36,520 --> 06:32:39,080 OR DELTA T-CELLS OR OTHER CELLS 8672 06:32:39,080 --> 06:32:41,760 YOU MIGHT WANT TO DRIVE. 8673 06:32:41,760 --> 06:32:45,800 YOU CAN SEE DIZZYING ARRAY OF 8674 06:32:45,800 --> 06:32:47,440 ENHANCEMENTS DEMONSTRATED IN 8675 06:32:47,440 --> 06:32:50,480 PRECLINICAL MODELS TO BE ACTIVE 8676 06:32:50,480 --> 06:32:53,120 AND SOME IN CLINIC SHOWN IN BOLD 8677 06:32:53,120 --> 06:32:54,440 THERE AND GUARANTEE YOU THIS 8678 06:32:54,440 --> 06:32:56,040 LIST IS OUT OF DATE AND EVERY 8679 06:32:56,040 --> 06:32:57,840 MONTH IS ANOTHER SET OF NEW WAYS 8680 06:32:57,840 --> 06:33:01,240 YOU CAN MAKE CELLS MORE POTENT 8681 06:33:01,240 --> 06:33:03,840 OR MORE REGULATABLE AND 8682 06:33:03,840 --> 06:33:04,640 THEREFORE POTENTIALLY MORE 8683 06:33:04,640 --> 06:33:07,640 EFFECTIVE. THIS IS AMAZING 8684 06:33:07,640 --> 06:33:09,200 MOMENTUM BY ANYBODY'S ACCOUNT. 8685 06:33:09,200 --> 06:33:12,120 GIVEN ALL THAT, WHAT COULD GO 8686 06:33:12,120 --> 06:33:15,040 WRONG. WHAT KEEPS SOME OF US UP 8687 06:33:15,040 --> 06:33:17,120 AT NIGHT. WELL, I THINK ONE 8688 06:33:17,120 --> 06:33:18,880 THING THAT IS A REAL PROBLEM 8689 06:33:18,880 --> 06:33:21,960 FACING OUR FIELD IS HOW IN THE 8690 06:33:21,960 --> 06:33:25,240 WORLD WILL WE ADDRESS THESE AND 8691 06:33:25,240 --> 06:33:26,760 FIGURE OUT WHICH ENHANCEMENTS 8692 06:33:26,760 --> 06:33:29,360 ARE RIGHT ONES TO STUDY AND HOW 8693 06:33:29,360 --> 06:33:31,240 WILL WE AVOID MISSING PERHAPS 8694 06:33:31,240 --> 06:33:33,000 THE BEST ONE AND IN CHASING THE 8695 06:33:33,000 --> 06:33:34,680 WRONG ONE AND I THINK THAT THE 8696 06:33:34,680 --> 06:33:37,600 FIRST THING CLEAR TO ME IS THAT 8697 06:33:37,600 --> 06:33:39,360 EVERY ONE OF THE ENHANCEMENTS 8698 06:33:39,360 --> 06:33:41,280 DEMONSTRATE TODAY BE EFFECTIVE 8699 06:33:41,280 --> 06:33:44,360 IN A MYRIAD MODEL CAN'T BE 8700 06:33:44,360 --> 06:33:45,200 TESTED CLINICALLY DON'T HAVE 8701 06:33:45,200 --> 06:33:47,680 ENOUGH PATIENTS OR MONEY OR 8702 06:33:47,680 --> 06:33:50,040 ENOUGH MANUFACTURING. 8703 06:33:50,040 --> 06:33:53,320 IT IS JUST NOT PRACTICAL TO BE 8704 06:33:53,320 --> 06:33:55,320 ABLE TO CONDUCT DIFFERENT 8705 06:33:55,320 --> 06:33:57,480 CLINICAL TRIAL TO TEST EVERY ONE 8706 06:33:57,480 --> 06:33:58,200 OF THE ENHANCEMENTS. 8707 06:33:58,200 --> 06:34:01,680 I THINK WE SHOULD THINK ABOUT 8708 06:34:01,680 --> 06:34:03,280 THESE PRECLINICAL STUDIES. 8709 06:34:03,280 --> 06:34:05,200 THEY NOT ONLY SHOULD THEY BE USE 8710 06:34:05,200 --> 06:34:08,480 TODAY CREATE NEW ENHANCEMENTS 8711 06:34:08,480 --> 06:34:10,600 BUT SOMEONE NEED TODZ CONDUCT 8712 06:34:10,600 --> 06:34:12,720 RIGOROUS PRECLINICAL STUDIES 8713 06:34:12,720 --> 06:34:15,680 NEED TODAY COMPARE ITERATIONS TO 8714 06:34:15,680 --> 06:34:16,560 PRIORITIZE. 8715 06:34:16,560 --> 06:34:18,200 THAT SOUNDS SIMPLE AND WE KNOW 8716 06:34:18,200 --> 06:34:20,040 HOW TO CERTAINLY DO THIS TYPE OF 8717 06:34:20,040 --> 06:34:23,920 WORK AND ARGUE THAT INCENTIVES 8718 06:34:23,920 --> 06:34:26,560 IN ACADEMIA AND IN INDUSTRY 8719 06:34:26,560 --> 06:34:28,520 DON'T REWARD COMPARISON STUDIES. 8720 06:34:28,520 --> 06:34:31,040 NOT AN EXTENT YOU DON'T SEE 8721 06:34:31,040 --> 06:34:31,880 COMPARATIVE STUDIES OUT THERE. 8722 06:34:31,880 --> 06:34:34,160 WHEN YOU DO THEY ARE WEIGHTED 8723 06:34:34,160 --> 06:34:35,760 TOWARDS ONE OR THE OTHER 8724 06:34:35,760 --> 06:34:36,960 ENHANCEMENTS BECAUSE OF BIAS OF 8725 06:34:36,960 --> 06:34:38,560 THE INVESTIGATORS. 8726 06:34:38,560 --> 06:34:43,480 I THINK THAT THE ACADEMIC ARENA 8727 06:34:43,480 --> 06:34:45,040 IN PARTICULAR IS -- HAS 8728 06:34:45,040 --> 06:34:47,760 HYPERFOCUS ON NOVELTY IN 8729 06:34:47,760 --> 06:34:50,280 ACADEMIC STUDY SECTIONS AND 8730 06:34:50,280 --> 06:34:51,920 GETTING GRANT FUNDED AND 8731 06:34:51,920 --> 06:34:53,920 DECIDING WHETHER PAPER IS 8732 06:34:53,920 --> 06:34:55,880 PUBLISHED AND EMPHASIS IS ON NEW 8733 06:34:55,880 --> 06:34:59,680 AND DIFFERENT AND THEMLE FASIS 8734 06:34:59,680 --> 06:35:01,520 MINIMIZES THE IMPORTANCE OF 8735 06:35:01,520 --> 06:35:03,960 CAREFUL COMPARATOR STUDIES THAT 8736 06:35:03,960 --> 06:35:05,440 WILL ADVANCE THE FIELD OVERALL 8737 06:35:05,440 --> 06:35:08,320 AND ALLOW US TO BE BETTER AT 8738 06:35:08,320 --> 06:35:09,000 PRIORITIZATION. 8739 06:35:09,000 --> 06:35:11,280 NOW, EVEN IF WE PRIORITIZE TO, 8740 06:35:11,280 --> 06:35:13,800 YOU KNOW, REALLY A LOT, WE HAVE 8741 06:35:13,800 --> 06:35:16,040 TO STILL BE ABLE TO HAVE GREATER 8742 06:35:16,040 --> 06:35:17,680 THROUGHPUT IN HUMAN TEXTING. 8743 06:35:17,680 --> 06:35:19,800 CAN'T DO THAT. WE DON'T HAVE 8744 06:35:19,800 --> 06:35:22,280 ACCESS TO VECTOR AND CLINICAL 8745 06:35:22,280 --> 06:35:25,360 NUCLEIC A** ID VIRAL PLATFORM 8746 06:35:25,360 --> 06:35:27,640 AND MONEY TO RUN CLINICAL TRIALS 8747 06:35:27,640 --> 06:35:29,400 WE OFTEN DON'T HAVE CAPACITY TO 8748 06:35:29,400 --> 06:35:31,760 DO MANUFACTURING NEEDED TO TEST 8749 06:35:31,760 --> 06:35:33,960 MULTIPLE ITERATIONS AND IF WE 8750 06:35:33,960 --> 06:35:36,520 HAD ALL OF THAT, CURRENT 8751 06:35:36,520 --> 06:35:39,160 REGULATORY PRACTICES DON'T ALLOW 8752 06:35:39,160 --> 06:35:42,480 ADMINISTRATION OF MIXED PRODUCTS 8753 06:35:42,480 --> 06:35:46,040 AS AN EXPERIMENTAL QUESTION IN 8754 06:35:46,040 --> 06:35:48,160 ORDER TO COMPARE FITNESS IN 8755 06:35:48,160 --> 06:35:49,600 HUMANS AND MIXED PRODUCTS ARE 8756 06:35:49,600 --> 06:35:51,760 PART OF WHAT WE ARE ALWAYS 8757 06:35:51,760 --> 06:35:54,560 ADMINISTERING AND I ARGUE THAT 8758 06:35:54,560 --> 06:35:56,000 ADMINISTERING MIXED PRODUCTS TO 8759 06:35:56,000 --> 06:35:58,080 WHAT WE CALL A BAKE OFF TO PICK 8760 06:35:58,080 --> 06:36:00,280 THE WINNER IS PROBABLY BEST WAY 8761 06:36:00,280 --> 06:36:02,560 TO REALLY KNOW WHICH CELLS ARE 8762 06:36:02,560 --> 06:36:04,480 MORE EFFECTIVE IN HUMANS. 8763 06:36:04,480 --> 06:36:06,320 SO, I THINK THAT WE NEED TO MAKE 8764 06:36:06,320 --> 06:36:10,000 THE CASE TO THE REGULATORS THAT 8765 06:36:10,000 --> 06:36:11,360 HETEROGENEITY IN AND OF ITSELF 8766 06:36:11,360 --> 06:36:14,560 IS NOT LIKELY TO INCREASE RISKS 8767 06:36:14,560 --> 06:36:18,560 SUBSTANTIALLY AND WE ADMINISTER 8768 06:36:18,560 --> 06:36:21,400 HETEROGENOUS PRODUCTS AND 8769 06:36:21,400 --> 06:36:23,320 ABILITY TO TEST SEVERAL OR MANY 8770 06:36:23,320 --> 06:36:25,960 ITERATIONS IN INDIVIDUAL 8771 06:36:25,960 --> 06:36:27,640 PATIENTS IS PART OF INDIVIDUAL 8772 06:36:27,640 --> 06:36:29,400 GRAPH WOULD BE INCREDIBLY 8773 06:36:29,400 --> 06:36:32,960 VALUABLE AND THIS NEXT 8774 06:36:32,960 --> 06:36:35,040 GENERATION CLINICAL TRIAL DESIGN 8775 06:36:35,040 --> 06:36:37,400 IN CORRELATIVE TESTING IS 8776 06:36:37,400 --> 06:36:40,360 CRITICAL TO ADDRESS THIS 8777 06:36:40,360 --> 06:36:41,920 CHALLENGE. WHAT ELSE COULD GO 8778 06:36:41,920 --> 06:36:42,760 WRONG? 8779 06:36:42,760 --> 06:36:44,560 WELL, THE OTHER POINT THAT KEEPS 8780 06:36:44,560 --> 06:36:48,440 ME UP AT NIGHT AND THIS ONE I 8781 06:36:48,440 --> 06:36:50,760 THINK IS NEAR AND DEAR TO HEARTS 8782 06:36:50,760 --> 06:36:52,320 OF EVERYBODY PARTICIPATING TODAY 8783 06:36:52,320 --> 06:36:54,920 IS BIOPHARMAMODEL THAT IS 8784 06:36:54,920 --> 06:36:56,640 DOMINATING THE SPACE AND MOVING 8785 06:36:56,640 --> 06:36:58,000 INTO FACE OF COMMERCIALIZATION 8786 06:36:58,000 --> 06:37:00,480 THAT CARIES WITH IT SUBSTANTIAL 8787 06:37:00,480 --> 06:37:02,880 RISK THAT CAR T-CELLS FOR RARE 8788 06:37:02,880 --> 06:37:05,280 INDICATIONS INCLUDING PEDIATRIC 8789 06:37:05,280 --> 06:37:06,480 CANCERS WILL JUST NEVER BE 8790 06:37:06,480 --> 06:37:07,880 DEVELOPED AND WHY DO I WORRY 8791 06:37:07,880 --> 06:37:08,680 ABOUT THIS? 8792 06:37:08,680 --> 06:37:11,040 LOOK AT CD22 CAR. 8793 06:37:11,040 --> 06:37:14,920 THIS IS CREATED, OPTIMIZED AND 8794 06:37:14,920 --> 06:37:17,360 TESTED ALL IN ACADEMIA AND 8795 06:37:17,360 --> 06:37:18,960 [INDISCERNIBLE] LED WORK IN MY 8796 06:37:18,960 --> 06:37:21,160 LAB AND THEY DID ALL OF THE HARD 8797 06:37:21,160 --> 06:37:24,200 WORK THAT IS COMPARING VARIOUS 8798 06:37:24,200 --> 06:37:26,520 ITERATIONS TO PICK WINNER IN 8799 06:37:26,520 --> 06:37:30,640 TERMS OF BINDER AND EPITOEP AND 8800 06:37:30,640 --> 06:37:33,360 A DESIGN. 8801 06:37:33,360 --> 06:37:38,520 TERRY FROOI AND NCI DID HARD 8802 06:37:38,520 --> 06:37:40,680 WORK RUNNING EARLY PHASE TRIALS 8803 06:37:40,680 --> 06:37:42,440 SHOWING THAT THIS HAD REAL 8804 06:37:42,440 --> 06:37:44,120 EFFICACY AND THIS WAS FOR 8805 06:37:44,120 --> 06:37:46,760 PATIENTS WHO LARGELY FAILED CD19 8806 06:37:46,760 --> 06:37:49,640 CAR THERAPY AND MANY WERE CD19 8807 06:37:49,640 --> 06:37:53,240 DIM AND YET 70% HAD CR MOST MRD 8808 06:37:53,240 --> 06:37:55,160 NEGATIVE THAT LED TO 8809 06:37:55,160 --> 06:37:56,080 BREAKTHROUGH THERAPY 8810 06:37:56,080 --> 06:37:58,440 DESIGNATION. THIS IS EXCITING 8811 06:37:58,440 --> 06:38:00,160 BUT DESPITE PROMISING DATA WE 8812 06:38:00,160 --> 06:38:03,320 ARE NOW 10 YEARS FROM THE 8813 06:38:03,320 --> 06:38:05,840 ORIGINAL PUBLICATION AND 8814 06:38:05,840 --> 06:38:06,760 REGISTRATIONAL TRIALS HAVE NOT 8815 06:38:06,760 --> 06:38:09,840 YET BEEN LAUNCHED BY BIOPHARMA. 8816 06:38:09,840 --> 06:38:12,680 I WILL TELL YOU FROM PERSONAL 8817 06:38:12,680 --> 06:38:13,760 EXPERIENCE THIS IS NOT FROM LACK 8818 06:38:13,760 --> 06:38:15,800 OF TRYING AND IT WILL GET 8819 06:38:15,800 --> 06:38:17,840 LAUNCHED AND WE WILL GET 8820 06:38:17,840 --> 06:38:21,320 REGISTRATION IN PEDIATRICS BUT 8821 06:38:21,320 --> 06:38:24,320 NOT AT SPEED AND PACE THAT 8822 06:38:24,320 --> 06:38:25,560 THERAPEUTIC DESERVED. 8823 06:38:25,560 --> 06:38:28,240 WHAT ABOUT SOLID TUMORS? 8824 06:38:28,240 --> 06:38:30,360 WE KNOW THAT IS WHERE GREATEST 8825 06:38:30,360 --> 06:38:33,760 NEED IS IN PEDIATRIC CANCERS WE 8826 06:38:33,760 --> 06:38:34,720 NEED BREAKTHROUGHS IN DISEASES 8827 06:38:34,720 --> 06:38:38,480 AND IN SUMMARY OF I THINK MOST 8828 06:38:38,480 --> 06:38:39,240 PROMISING DATA THROUGHOUT FOR 8829 06:38:39,240 --> 06:38:42,120 CAR T-CELLS AND SOLID TUMORS ARE 8830 06:38:42,120 --> 06:38:45,720 9 DIFFERENT STUDIES THAT ARE 8831 06:38:45,720 --> 06:38:49,160 NOTED. OF THESE, 4, COUNT THEM 8832 06:38:49,160 --> 06:38:52,000 4 ARE IN PEDIATRIC INDICATION. 8833 06:38:52,000 --> 06:38:54,960 AND 7 OF THE 9 ARE ACADEMIC 8834 06:38:54,960 --> 06:38:55,560 STUDIES. 8835 06:38:55,560 --> 06:38:57,760 AGAIN, HIGHLIGHTING CRITICAL AND 8836 06:38:57,760 --> 06:39:00,480 EFFECTIVE ROLE THATTACDEMIA CAN 8837 06:39:00,480 --> 06:39:02,440 HAVE IN DEVELOPING AND 8838 06:39:02,440 --> 06:39:04,040 DELIVERING NOVEL THERAPEUTICS 8839 06:39:04,040 --> 06:39:09,520 WHEN COMING TO SELLING GENE 8840 06:39:09,520 --> 06:39:09,800 THERAPY. 8841 06:39:09,800 --> 06:39:12,880 SO, WHAT CAN GO WRONG? IT IS 8842 06:39:12,880 --> 06:39:17,040 THAT BIOPHARMAMODEL DOMINATING 8843 06:39:17,040 --> 06:39:20,120 THE SPACE CARIES WITH IT THIS 8844 06:39:20,120 --> 06:39:21,680 RISK THAT RARE INDICATIONS WILL 8845 06:39:21,680 --> 06:39:22,880 NOT GET DEVELOPED. 8846 06:39:22,880 --> 06:39:24,960 AND THIS IS EASY TO UNDERSTAND. 8847 06:39:24,960 --> 06:39:28,520 THE HIGH COSTS AND HIGH RISKS IN 8848 06:39:28,520 --> 06:39:30,240 BIOPHARMAFOR DEVELOPING CELL AND 8849 06:39:30,240 --> 06:39:32,920 GENE THERAPIES DIMINISH FOCUS ON 8850 06:39:32,920 --> 06:39:35,120 RARE DISEASES AND TRUTH IS 500 8851 06:39:35,120 --> 06:39:36,840 COMPANIES IN THE US, EVERY ONE 8852 06:39:36,840 --> 06:39:39,800 OF THEM HAS TO SURVIVE. IF THEY 8853 06:39:39,800 --> 06:39:42,440 INVEST PRECIOUS DOLLARS IN RARE 8854 06:39:42,440 --> 06:39:44,640 INDICATIONS CHANCE OF GETTING 8855 06:39:44,640 --> 06:39:46,440 GREATER INVESTMENT SUSTAINING 8856 06:39:46,440 --> 06:39:49,200 RUNWAY DIMINISHES. THIS IS NOT 8857 06:39:49,200 --> 06:39:51,880 UNIQUE TO CAR T-CELLS FOR SOLID 8858 06:39:51,880 --> 06:39:53,760 OR LIQUID TUMORS AND SIMILAR 8859 06:39:53,760 --> 06:39:55,800 MARKET FAILURE IS OCCURRING IN 8860 06:39:55,800 --> 06:39:58,120 DEVELOPMENT OF CELL AND GENE 8861 06:39:58,120 --> 06:39:59,560 THERAPIES FOR NONMALIGNANT 8862 06:39:59,560 --> 06:40:01,080 DISEASES OCCURRING IN CHILDREN 8863 06:40:01,080 --> 06:40:03,160 AND FOR MOST PART THESE ARE 8864 06:40:03,160 --> 06:40:07,120 RARE. THIS HAS BEEN REALLY 8865 06:40:07,120 --> 06:40:08,520 CHALLENGING FOR DEVELOPMENT OF 8866 06:40:08,520 --> 06:40:10,440 GENE THERAPY AND 8867 06:40:10,440 --> 06:40:13,520 IMMUNODEFICIENCIES AND NEUR 8868 06:40:13,520 --> 06:40:15,040 LOGIC DISEASE AND IN ADDRESSING 8869 06:40:15,040 --> 06:40:17,800 THIS PROBLEM IS DEVELOPMENT OF 8870 06:40:17,800 --> 06:40:20,720 NEW INITIATIVE IN UK 8871 06:40:20,720 --> 06:40:21,360 AGORAINITIATIVE GOAL TO BRING 8872 06:40:21,360 --> 06:40:23,560 GENE THERAPIES TO MARKET FOR 8873 06:40:23,560 --> 06:40:25,800 RARE DISEASE USING NEW MODELS 8874 06:40:25,800 --> 06:40:27,480 AND PUBLIC AND PRIVATE 8875 06:40:27,480 --> 06:40:28,680 PARTNERSHIPS, ET CETERA. IF 8876 06:40:28,680 --> 06:40:30,160 INTERESTED IN THIS I ENCOURAGE 8877 06:40:30,160 --> 06:40:34,440 YOU TO READ IN RECENT ARTICLE IN 8878 06:40:34,440 --> 06:40:36,800 NATURE MEDICINE AND JUST A WEEK 8879 06:40:36,800 --> 06:40:41,600 OR 2 BACK. DISCUSSING THIS 8880 06:40:41,600 --> 06:40:43,240 INITIATIVE. I THINK THAT YOU 8881 06:40:43,240 --> 06:40:45,400 KNOW SCIENTIFIC PROGRESS THAT 8882 06:40:45,400 --> 06:40:46,800 HORSE IS OUT OF THE BARN AND 8883 06:40:46,800 --> 06:40:48,480 THIS WILL CONTINUE TO ADVANCE. 8884 06:40:48,480 --> 06:40:51,680 WHAT WILL BE DIFFICULT IS 8885 06:40:51,680 --> 06:40:54,560 FIGURING OUT WHICH OF THOSE 8886 06:40:54,560 --> 06:40:56,880 GREAT PRECLINICAL MANUSCRIPTS 8887 06:40:56,880 --> 06:40:59,000 MERIT CLINICAL TESTING AND HOW 8888 06:40:59,000 --> 06:41:00,920 DO WE INCREASE THROUGH PUT OF 8889 06:41:00,920 --> 06:41:02,760 CLINICAL TESTING TO LEARN MOST 8890 06:41:02,760 --> 06:41:04,720 FROM LEAST NUMBER OF PATIENTS? 8891 06:41:04,720 --> 06:41:08,200 HOW DO WE PREVENT PEDIATRICS 8892 06:41:08,200 --> 06:41:11,920 FROM BEING LEFT OUT OF THIS 8893 06:41:11,920 --> 06:41:20,520 REMARKABLE SUCCESS STORY THAT IS 8894 06:41:20,520 --> 06:41:23,240 CAR T-CELLS AND CELL GENE 8895 06:41:23,240 --> 06:41:24,840 THERAPIES WRIT LARGE. LOOK 8896 06:41:24,840 --> 06:41:27,840 FORWARD TO WORKING WITH YOU STAY 8897 06:41:27,840 --> 06:41:31,480 TUNED WHAT IS NEW IN PEDIATRICS 8898 06:41:31,480 --> 06:41:33,320 AND WHAT WILL BE CRITICAL I HOPE 8899 06:41:33,320 --> 06:41:36,240 IN MAKING SURE KIDS DON'T GET 8900 06:41:36,240 --> 06:41:37,560 LEFT OUT AND THANKS FOR 8901 06:41:37,560 --> 06:41:39,240 OPPORTUNITY TO GIVE CLOSING 8902 06:41:39,240 --> 06:41:40,720 REMARKS AND HOPE THEY WERE OF 8903 06:41:40,720 --> 06:41:46,960 INTEREST. THANK YOU. BYE, BYE. 8904 06:41:46,960 --> 06:41:49,000 >> [APPLAUSE]. 8905 06:41:49,000 --> 06:41:53,360 >> KRYSTAL, DO WE HAVE ANY 8906 06:41:53,360 --> 06:41:54,880 COMMENTS TO MAKE? MIGHT GO 8907 06:41:54,880 --> 06:42:03,600 RIGHT TO THE NEXT SPEAKER. 8908 06:42:03,600 --> 06:42:05,680 I WILL GO AHEAD. I HAVE 8909 06:42:05,680 --> 06:42:09,760 PLEASURE OF INTRODUCING STEVEN 8910 06:42:09,760 --> 06:42:14,680 GOD CHALK. BEFORE JOINING ST. 8911 06:42:14,680 --> 06:42:18,960 JUDE IN 2017 CHAIR OF DEPARTMENT 8912 06:42:18,960 --> 06:42:24,000 -- HE ACTIVELY CONDUCTS 8913 06:42:24,000 --> 06:42:26,280 INVESTIGATOR INITIATED EARLY 8914 06:42:26,280 --> 06:42:29,240 PHASE CLINICAL TRIALS AND 8915 06:42:29,240 --> 06:42:31,600 OVERSEES PHD RESEARCHERS WORKING 8916 06:42:31,600 --> 06:42:33,640 ON MULTIPLE RESEARCH PROJECTS 8917 06:42:33,640 --> 06:42:35,880 OVERCOMING LIMITATIONS FOR 8918 06:42:35,880 --> 06:42:39,080 ADOPTIVE CELL THERAPY FOR CANCER 8919 06:42:39,080 --> 06:42:42,720 AND CO-LEADS TRANSLATIONAL 8920 06:42:42,720 --> 06:42:44,400 COTHERAPY AT ST. JUDE OF 8921 06:42:44,400 --> 06:42:46,080 SCIENTISTS AND ACADEMIC 8922 06:42:46,080 --> 06:42:47,720 PHYSICIANS AND WILL HEAR ABOUT 8923 06:42:47,720 --> 06:42:51,440 HIS TALK OF PONDERING FUTURE OF 8924 06:42:51,440 --> 06:42:55,760 CAR T-CELLS. 8925 06:42:55,760 --> 06:42:58,280 >> THANK YOU. I WOULD LIKE TO 8926 06:42:58,280 --> 06:43:00,840 THANK ORGANIZER PARTICULARLY TO 8927 06:43:00,840 --> 06:43:05,960 ORGANIZE MEETING AND INVITE ME 8928 06:43:05,960 --> 06:43:07,760 GIVING TITLE SHE TOLD ME AS LONG 8929 06:43:07,760 --> 06:43:12,680 AS PONDERING IS POSITIVE I CAN 8930 06:43:12,680 --> 06:43:16,080 GIVE TALK IS. 8931 06:43:16,080 --> 06:43:20,800 AT ANY RATE THEY ARE MY 8932 06:43:20,800 --> 06:43:31,120 DISCLOSURES AND. 8933 06:43:31,840 --> 06:43:34,120 SO, YOU KNOW, IT HAS BEEN 30 8934 06:43:34,120 --> 06:43:36,320 YEARS SINCE I PUT UP THE SLIDE 8935 06:43:36,320 --> 06:43:39,120 AND TWO GROUPS FROM INVESTIGATOR 8936 06:43:39,120 --> 06:43:42,480 DESIGNS THAT WE CURRENTLY KNOW 8937 06:43:42,480 --> 06:43:48,000 IT AND TOM BROKER AND OVER THE 8938 06:43:48,000 --> 06:43:51,120 YEARS THERE HAS BEEN CONTINUOUS 8939 06:43:51,120 --> 06:43:52,680 RESIGN OF MOLECULES THAT I THINK 8940 06:43:52,680 --> 06:43:56,160 ARE STILL -- I WOULD SAY 8941 06:43:56,160 --> 06:43:57,520 NOVELTIES THAT COME UP AND ARE 8942 06:43:57,520 --> 06:44:04,600 VERY EXCITING AND ONE STORY IS 8943 06:44:04,600 --> 06:44:08,200 ROBBY'S STORY REPLACING THE 8944 06:44:08,200 --> 06:44:11,440 SINGLE DOMAIN SHOT CIRCUITING 8945 06:44:11,440 --> 06:44:14,440 THE SINGLING MACHINERY AND WE 8946 06:44:14,440 --> 06:44:16,640 RECENTLY PUBLISHED ARTICLE 8947 06:44:16,640 --> 06:44:25,920 ADDING PBC BINDING DOMAIN 8948 06:44:25,920 --> 06:44:29,520 DRAMATICALLY ENHANCING SIGN UPS 8949 06:44:29,520 --> 06:44:32,480 WITH CARS AND FIRST CHIME ERIC 8950 06:44:32,480 --> 06:44:33,760 RECEPTOR CONSISTING OF TWO GENES 8951 06:44:33,760 --> 06:44:37,200 WAS REALLY CREATED BY 8952 06:44:37,200 --> 06:44:38,560 [INDISCERNIBLE] GROUP AND WAS 8953 06:44:38,560 --> 06:44:43,400 QUITE AMAZING AND 1987 AND THREE 8954 06:44:43,400 --> 06:44:45,480 YEARS AFTER T RECEPTORS ARE 8955 06:44:45,480 --> 06:44:47,160 CLONED AND BRINGING UP BECAUSE 8956 06:44:47,160 --> 06:44:49,960 YOU SHOULD LOOK AT DESIGN AND 8957 06:44:49,960 --> 06:44:52,320 SAY THIS SOUNDS FAMILIAR. 8958 06:44:52,320 --> 06:44:56,120 RECENTLY RECEPTORS ARE 8959 06:44:56,120 --> 06:44:58,080 REINTRODUCED AGAIN BY JEN'S 8960 06:44:58,080 --> 06:45:01,120 GROUP AND ALSO MICHELLE'S GROUP 8961 06:45:01,120 --> 06:45:04,320 AND NOWADAYS OR TODAY WE NOT 8962 06:45:04,320 --> 06:45:08,400 ONLY HAVE STANDARD CAR BUT HAVE 8963 06:45:08,400 --> 06:45:09,800 MULTIPLE SYNTHETIC MOLECULES 8964 06:45:09,800 --> 06:45:12,200 THAT IN THE END TAKE ADVANTAGE 8965 06:45:12,200 --> 06:45:14,560 OF THE ENTIRE T-CELL RECEPTOR 8966 06:45:14,560 --> 06:45:16,840 COMPLEX AND PROBABLY THE BIGGEST 8967 06:45:16,840 --> 06:45:20,280 ADVANTAGE OF THESE DESIGNS ARE 8968 06:45:20,280 --> 06:45:24,680 THAT THEY HAVE INCREASED 8969 06:45:24,680 --> 06:45:25,560 ANCONTINUALEN SENSITIVITY AND TO 8970 06:45:25,560 --> 06:45:28,040 MY KNOWLEDGE ONLY GROUP THAT 8971 06:45:28,040 --> 06:45:29,640 CAREFULLY MANAGED THAT IS 8972 06:45:29,640 --> 06:45:31,520 MICHELLE AND LOOKS LIKE 8973 06:45:31,520 --> 06:45:34,320 RECEPTORS ARE 10 FOLD MORE 8974 06:45:34,320 --> 06:45:38,560 SENSITIVE THAN COMPARABLE CAR 8975 06:45:38,560 --> 06:45:42,160 FOR DETECTING SAME ANTIGEN ON 8976 06:45:42,160 --> 06:45:43,840 CELL SURFACE OF TARGET CELLS AND 8977 06:45:43,840 --> 06:45:46,320 RIGHT NOW TO MY KNOWLEDGE THERE 8978 06:45:46,320 --> 06:45:50,040 IS NONE OF THESE NOVEL T-CELL 8979 06:45:50,040 --> 06:45:52,320 RECEPTOR DESIGNS BEING EXPLORED 8980 06:45:52,320 --> 06:45:56,040 IN PEDIATRIC SPACE. 8981 06:45:56,040 --> 06:46:02,560 IF YOU LOOK AT SOLID TUMOR CAR 8982 06:46:02,560 --> 06:46:05,320 T-CELLS PEDIATRIC CANCER WE LIVE 8983 06:46:05,320 --> 06:46:07,080 IN WORLD WHERE MAJORITY OF 8984 06:46:07,080 --> 06:46:10,200 STUDIES CONDUCT TARGETED ANTIGEN 8985 06:46:10,200 --> 06:46:14,560 AND IS TREMENDOUS NEED TO 8986 06:46:14,560 --> 06:46:19,000 DISCOVER ANCONTINUALENS AND 8987 06:46:19,000 --> 06:46:20,720 THESE ARE ALREADY MENTIONED AND 8988 06:46:20,720 --> 06:46:22,320 WE THOUGHT TO TAKE A LITTLE 8989 06:46:22,320 --> 06:46:24,440 DIFFERENT APPROACH. WE PUT 8990 06:46:24,440 --> 06:46:27,760 TOGETHER PROBABLY ONE OF THE 8991 06:46:27,760 --> 06:46:30,480 LARGEST COHORTS OF PEDIATRIC 8992 06:46:30,480 --> 06:46:32,120 SOLID TUMORS AND BRAIN TUMORS 8993 06:46:32,120 --> 06:46:33,920 DEVELOPING A PIPELINE TO NOT 8994 06:46:33,920 --> 06:46:37,400 ONLY LOOK AT DIFFERENTIALLY 8995 06:46:37,400 --> 06:46:38,000 EXPRESSED ANCONTINUALENS BUT 8996 06:46:38,000 --> 06:46:40,920 ALSO ASKED QUESTIONS ARE THERE 8997 06:46:40,920 --> 06:46:42,840 CANCER SPECIFIC ISOFORMS THAT 8998 06:46:42,840 --> 06:46:46,680 COULD BE TARGETED? 8999 06:46:46,680 --> 06:46:55,400 AND YOU KNOW WITH HELP RUNNING 9000 06:46:55,400 --> 06:46:56,080 COMPUTATIONAL BIOLOGY DEPARTMENT 9001 06:46:56,080 --> 06:46:58,320 TEAM DEVELOPED A VERY NICE 9002 06:46:58,320 --> 06:47:00,240 PIPELINE FOR US AND IN END WE 9003 06:47:00,240 --> 06:47:03,880 ENDED UP MAINLY DIFFERENTIALLY 9004 06:47:03,880 --> 06:47:07,040 EXPRESSED GENES AND ALSO SEVERAL 9005 06:47:07,040 --> 06:47:09,800 9 GENES WE DISCOVERED AND 9006 06:47:09,800 --> 06:47:11,560 DETECTED CANCER SPECIFIC 9007 06:47:11,560 --> 06:47:14,520 ISOFORMS LOOKING AT VERY HIGH 9008 06:47:14,520 --> 06:47:16,160 LEVEL USING A HEAT MAP FOR TIER 9009 06:47:16,160 --> 06:47:18,800 1 TARGETS IS NOT ALL CLEAN AND 9010 06:47:18,800 --> 06:47:21,960 CLEARLY A LOT OF THE TARGETS ARE 9011 06:47:21,960 --> 06:47:24,200 HIGH EXPRESSING SOLID TUMORS AND 9012 06:47:24,200 --> 06:47:27,120 BRAIN TUMORS AND SOME TARGETS 9013 06:47:27,120 --> 06:47:29,720 ARE REALLY VERY INTERESTING AND 9014 06:47:29,720 --> 06:47:31,440 ARE NOT REALLY CELL SURFACE 9015 06:47:31,440 --> 06:47:35,240 TARGETS THAT I EXPRESSED IN 9016 06:47:35,240 --> 06:47:38,520 EXTRA CELLULAR MATRIX INCLUDING 9017 06:47:38,520 --> 06:47:43,240 A1 SPLICE VARIANT OF 9018 06:47:43,240 --> 06:47:45,440 [INDISCERNIBLE] PUBLISHING WORK 9019 06:47:45,440 --> 06:47:52,960 ON TARGETING SPLICE VARIANT OF 9020 06:47:52,960 --> 06:47:54,720 HOOIFERMECTIN AND THESE ARE 9021 06:47:54,720 --> 06:47:58,560 SECRETED AND LOTS HAVE RGD 9022 06:47:58,560 --> 06:48:00,200 DOMAINS THAT BIND INTEGRIN 9023 06:48:00,200 --> 06:48:03,120 BINDING BACK TO TARGET CELLS AND 9024 06:48:03,120 --> 06:48:05,720 ARE THERE FOR SENSITIVE TO CAR 9025 06:48:05,720 --> 06:48:08,440 T-CELLS TARGETING SPECIFIC 9026 06:48:08,440 --> 06:48:12,640 ISOFORMS AND WE HAVE SHOWN THAT 9027 06:48:12,640 --> 06:48:13,840 THESE CELLS HAVE SIGNIFICANT 9028 06:48:13,840 --> 06:48:17,880 ANTITOMB ERIC ACTIVITY AND TUMOR 9029 06:48:17,880 --> 06:48:21,320 VASCULAR ACTIVITY IN PRECLINICAL 9030 06:48:21,320 --> 06:48:21,720 MODEL. 9031 06:48:21,720 --> 06:48:24,240 FOR COALO LEVEL A1, WE REALLY 9032 06:48:24,240 --> 06:48:27,400 ARE INTRIGUED BY THIS PARTICULAR 9033 06:48:27,400 --> 06:48:30,360 ECM PROTEIN. IT IS VERY CLEAN 9034 06:48:30,360 --> 06:48:31,560 AND THERE IS ALMOST NO 9035 06:48:31,560 --> 06:48:33,880 EXPRESSION IN NORMAL TISSUE THAT 9036 06:48:33,880 --> 06:48:38,440 IS HIGHLY EXPRESSED IN OSTEOSAR 9037 06:48:38,440 --> 06:48:41,960 COMBA AND TARGETS LOOKING IN 9038 06:48:41,960 --> 06:48:43,400 LITERATURE YOU CAN FIND THEM 9039 06:48:43,400 --> 06:48:46,440 COALO LEVEL A1 IS EXPRESSED IN 9040 06:48:46,440 --> 06:48:48,320 STROMA OF BREAST CANCER AND P 9041 06:48:48,320 --> 06:48:50,360 DABBING AND ARE QUITE LUCKY AND 9042 06:48:50,360 --> 06:48:54,520 THERE IS COMPANY DEVELOPED WITH 9043 06:48:54,520 --> 06:48:57,520 DIAGNOSTIC ANTIBODY TO PROTECT 9044 06:48:57,520 --> 06:49:01,200 THIS LEVEL OF A1 USED TO 9045 06:49:01,200 --> 06:49:03,040 GENERATE A CAR AND THESE T-CELLS 9046 06:49:03,040 --> 06:49:06,760 IN PRELIMINARY ANALYSIS 9047 06:49:06,760 --> 06:49:11,040 RECOGNIZE PEDIATRIC -- AND ALSO 9048 06:49:11,040 --> 06:49:15,040 HAVE SIGNIFICANT ANTI-TOMB ERIC 9049 06:49:15,040 --> 06:49:19,080 ACTIVITY IN SOME PRECLINICAL 9050 06:49:19,080 --> 06:49:19,800 MODELS. 9051 06:49:19,800 --> 06:49:21,840 AS ALREADY MENTIONED CAR T-CELLS 9052 06:49:21,840 --> 06:49:25,120 ARE BEING NOW EXPLORED TO TARGET 9053 06:49:25,120 --> 06:49:27,920 PEPTIDES IN CONTEXT OF HLA 9054 06:49:27,920 --> 06:49:30,560 MOLECULE AND MUST ADMIT I AM 9055 06:49:30,560 --> 06:49:32,560 ALWAYS SKEPTICAL AND AS LONG AS 9056 06:49:32,560 --> 06:49:35,640 WE GET HOA RESTRICTION BACK WE 9057 06:49:35,640 --> 06:49:38,280 CANNOT DO THESE STUDIES IN 9058 06:49:38,280 --> 06:49:40,360 PEDIATRIC CANCER AND GOOD 9059 06:49:40,360 --> 06:49:43,600 EXAMPLE IS BY TCR STUDY AND FOR 9060 06:49:43,600 --> 06:49:46,480 THIS SAR COMBA THAT IS HLA 9061 06:49:46,480 --> 06:49:48,360 RESTRICTED AND KRYSTAL WILL TELL 9062 06:49:48,360 --> 06:49:52,080 YOU TO INVOLVE ONE PATIENT PER 9063 06:49:52,080 --> 06:49:54,400 YEAR AND AT LEAST THESE ARE 9064 06:49:54,400 --> 06:49:57,480 GENERATED AND PEPTIDES ACTUALLY 9065 06:49:57,480 --> 06:50:01,120 ARE SVS RECOGNIZE PEPTIDES IN 9066 06:50:01,120 --> 06:50:03,760 CONTEXT OF MULTIPLE HA TYPES AND 9067 06:50:03,760 --> 06:50:06,360 IF THAT CAN REALLY BE APPLIED TO 9068 06:50:06,360 --> 06:50:08,560 MORE PEPTIDES I THINK THESE TYPE 9069 06:50:08,560 --> 06:50:11,200 OF APPROACHES WILL BE FEASIBLE 9070 06:50:11,200 --> 06:50:13,000 IN THE PEDIATRIC SPACE AND ARE 9071 06:50:13,000 --> 06:50:18,120 NOT RESTRICTIVE TO A SINGLE HOA 9072 06:50:18,120 --> 06:50:23,400 MOLECULE AND OF COURSE THERE ARE 9073 06:50:23,400 --> 06:50:25,840 SYNTHETIC APPROACHES USING THESE 9074 06:50:25,840 --> 06:50:27,880 AND ALSO THE FOREMENTIONED I 9075 06:50:27,880 --> 06:50:32,440 WOULD CALL IT SEQUENTIAL OR 9076 06:50:32,440 --> 06:50:36,080 ZENGATE THAT IS A BEST EXAMPLE 9077 06:50:36,080 --> 06:50:41,960 RIGHT NOW THAT IS A SYSTEM. 9078 06:50:41,960 --> 06:50:46,360 WHAT ABOUT ADDITIONAL GENETIC 9079 06:50:46,360 --> 06:50:48,480 MODIFICA 9080 06:50:48,480 --> 06:50:48,800 MODIFICATION. 9081 06:50:48,800 --> 06:50:52,080 TAKING CELLS EX-VIVO RECURSIVELY 9082 06:50:52,080 --> 06:50:56,080 EXPOSE IT TO T-CELLS INVARIABLY 9083 06:50:56,080 --> 06:50:58,080 T-CELLS CONTRACT AND WE WANT TO 9084 06:50:58,080 --> 06:51:00,640 BE IN SPACE WHERE THERE IS 9085 06:51:00,640 --> 06:51:04,760 CONTINUING ANTIGEN DEPENDENT 9086 06:51:04,760 --> 06:51:08,920 T-CELL EXPANSION. 9087 06:51:08,920 --> 06:51:10,520 CONCEPTUALLY YOU CAN DO TWO 9088 06:51:10,520 --> 06:51:12,640 THINGS, DO SCREENS AND TRY TO 9089 06:51:12,640 --> 06:51:17,640 DELETE NEGATIVE REGULATORS OR 9090 06:51:17,640 --> 06:51:19,800 OVEREXPRESS MOLECULES LIKE 9091 06:51:19,800 --> 06:51:23,680 TRANSCRIPTION FACTORS CYTOKINES 9092 06:51:23,680 --> 06:51:28,360 OR CHIM ERIC CYTOKINE RECEPTORS 9093 06:51:28,360 --> 06:51:32,240 TO ENHANCE AND PUT PEDAL TO THE 9094 06:51:32,240 --> 06:51:33,880 METAL AND TRY TO EXPAND 9095 06:51:33,880 --> 06:51:35,880 YOURSELVES AND WE HAVE BEEN VERY 9096 06:51:35,880 --> 06:51:39,520 INTERESTED IN EPIGENETIC 9097 06:51:39,520 --> 06:51:41,400 MODULATION AND THERE IS NO DOUBT 9098 06:51:41,400 --> 06:51:46,360 IF YOU LOOK ACROSS MIRRORING 9099 06:51:46,360 --> 06:51:47,960 HUMAN STUDIES NOW T-CELL 9100 06:51:47,960 --> 06:51:53,600 PLASTICITY IS DRIVEN BY HISTYOEN 9101 06:51:53,600 --> 06:51:54,800 MODIFICATIONS AND DNA 9102 06:51:54,800 --> 06:51:55,920 MODIFICATION AND HAVE BEEN 9103 06:51:55,920 --> 06:51:58,840 PARTICULARLY INTERESTED IN DMT3A 9104 06:51:58,840 --> 06:52:01,320 THAT HAS TO DO REALLY WITH 9105 06:52:01,320 --> 06:52:04,680 COLLABORATORS THAT WHEN HE WAS A 9106 06:52:04,680 --> 06:52:11,080 POST DOC IN LAB DEMONSTRATED IF 9107 06:52:11,080 --> 06:52:14,760 YOU KNOCK OUT IN T-CELLS YOU CAN 9108 06:52:14,760 --> 06:52:16,680 PREVENT TERMINAL EXHAUSTION AND 9109 06:52:16,680 --> 06:52:19,720 THESE CELLS ARE SENSITIVE TO 9110 06:52:19,720 --> 06:52:25,720 CHECK POINTS AND DEVELOPING 9111 06:52:25,720 --> 06:52:28,320 MULTIPOTENCY BASE WHERE NAÏVE 9112 06:52:28,320 --> 06:52:30,280 CELLS GET SCORE OF 1 AND 9113 06:52:30,280 --> 06:52:32,640 TERMINALLY DIFFERENTIATED CELLS 9114 06:52:32,640 --> 06:52:35,800 GET SCORE OF 0 AND TOGETHER WITH 9115 06:52:35,800 --> 06:52:42,240 THEM THERE IS A SAMPLE OF CD9 9116 06:52:42,240 --> 06:52:44,480 CAR T-CELL THERAPY THAT WAS 9117 06:52:44,480 --> 06:52:48,000 DEVELOPED BY AMY TELURE TO ASK 9118 06:52:48,000 --> 06:52:50,360 WHAT HAPPENED TO METHYLATION 9119 06:52:50,360 --> 06:52:53,400 PROGRAMS AFTER INFUSION OF 9120 06:52:53,400 --> 06:52:53,680 T-CELLS. 9121 06:52:53,680 --> 06:52:57,080 FIRST OF ALL LOOKING AT 9122 06:52:57,080 --> 06:53:00,240 MULTIPOTENCY INDEX OF PRODUCT TO 9123 06:53:00,240 --> 06:53:06,440 MY SURPRISE CELLS ARE NOT TOO 9124 06:53:06,440 --> 06:53:09,400 SHABBY AND INTERESTINGLY 9125 06:53:09,400 --> 06:53:11,880 MULTIPOTENCY INDEX CORRELATED 9126 06:53:11,880 --> 06:53:17,160 WITH PEAK EXPANSION OF INFUSED 9127 06:53:17,160 --> 06:53:17,400 CELLS. 9128 06:53:17,400 --> 06:53:23,640 NOW LOOKING AT WHAT HAPPENED IN 9129 06:53:23,640 --> 06:53:26,640 VIVO USING PCA ANALYSIS AND 9130 06:53:26,640 --> 06:53:29,200 FIRST TO ORIENT YOU ON THESE 9131 06:53:29,200 --> 06:53:30,920 CELLS AT BOTTOM THAT ARE 9132 06:53:30,920 --> 06:53:34,360 EXHAUSTED CELLS AND IN THE 9133 06:53:34,360 --> 06:53:38,800 MIDDLE ARE PRECURSOR EXHAUSTED 9134 06:53:38,800 --> 06:53:40,480 T-CELLS THAT ARE CALLED T PACKS 9135 06:53:40,480 --> 06:53:43,080 AND Z CELLS IN MODELS AND KNOW 9136 06:53:43,080 --> 06:53:45,480 HUMAN STUDIES THAT HAVE BEEN 9137 06:53:45,480 --> 06:53:49,280 IDENTIFIED AS CRITICAL SUBSET. 9138 06:53:49,280 --> 06:53:51,720 T PECHL CAN GIVE RISE TO 9139 06:53:51,720 --> 06:53:53,720 FUNCTIONAL EFFECTOR CELLS WHILE 9140 06:53:53,720 --> 06:53:55,520 IF YOU EXHAUST EVEN CHECKPOINT 9141 06:53:55,520 --> 06:53:57,240 LOCATED DOES NOT HELP YOU 9142 06:53:57,240 --> 06:53:57,560 ANYMORE. 9143 06:53:57,560 --> 06:54:01,080 IF YOU NOW LOOKING WHERE YOUR 9144 06:54:01,080 --> 06:54:03,920 CELLS ARE TO GNP PRODUCT IS 9145 06:54:03,920 --> 06:54:07,760 CLOSELY TO NAÏVE CELLS AND WITH 9146 06:54:07,760 --> 06:54:10,080 INFUSION OVER TIME WEEK 1, 2, 9147 06:54:10,080 --> 06:54:16,160 AND 3 SAMPLES, YOU GET A 9148 06:54:16,160 --> 06:54:17,000 PROGRESSIVE DECLINE. 9149 06:54:17,000 --> 06:54:19,480 IN PLASTICITY OF THE CELLS AND 9150 06:54:19,480 --> 06:54:22,000 BASED ON THESE RESULTS WE ARE 9151 06:54:22,000 --> 06:54:25,680 NOW ACTUALLY DEVELOPING A STUDY 9152 06:54:25,680 --> 06:54:28,080 KNOCKING OUT IN LEUKEMIA 9153 06:54:28,080 --> 06:54:31,960 SPECIFIC CAR T-CELLS AND WE WILL 9154 06:54:31,960 --> 06:54:33,000 EVALUATE THEIR FUNCTION. 9155 06:54:33,000 --> 06:54:36,600 LAST BUT NOT LEAST, I THINK THAT 9156 06:54:36,600 --> 06:54:39,600 ROBBY ALREADY MENTIONED IT AND 9157 06:54:39,600 --> 06:54:40,840 COMBINATORY THERAPY AND I 9158 06:54:40,840 --> 06:54:42,040 STRONGLY BELIEVE YOU HAVE TO 9159 06:54:42,040 --> 06:54:44,720 TEST SOME OF THESE IN 9160 06:54:44,720 --> 06:54:46,560 PRECLINICAL MODELS AND CLINICAL 9161 06:54:46,560 --> 06:54:48,320 STUDIES ARE JUST TOO EXPENSIVE 9162 06:54:48,320 --> 06:54:51,080 AND I JUST AS A TEASER I WANT TO 9163 06:54:51,080 --> 06:54:54,880 REALLY SHOW WORK FROM DALIA THAT 9164 06:54:54,880 --> 06:54:57,480 ROBBY MENTIONED IS IN 9165 06:54:57,480 --> 06:54:58,320 [INDISCERNIBLE] WHEN SHE WAS IN 9166 06:54:58,320 --> 06:55:01,000 LAB AND IS A QUESTION WHAT 9167 06:55:01,000 --> 06:55:03,200 REALLY HAPPENS DEPLETING 9168 06:55:03,200 --> 06:55:06,640 MICROPHAGES AND USING CSF 9169 06:55:06,640 --> 06:55:07,760 INHIBITOR AND IN GS 9170 06:55:07,760 --> 06:55:09,920 [INDISCERNIBLE] MODELS AND 9171 06:55:09,920 --> 06:55:12,080 INHIBITORS WORK NICELY AND WITH 9172 06:55:12,080 --> 06:55:16,160 REDUCTION OF TUMOR ASSOCIATED 9173 06:55:16,160 --> 06:55:19,640 MACROPHAGES AND THEN IF SHE 9174 06:55:19,640 --> 06:55:22,400 TESTED SEVERAL APPROACHES EITHER 9175 06:55:22,400 --> 06:55:23,880 CO-COMMITIENTLY GIVING INHIBITOR 9176 06:55:23,880 --> 06:55:26,120 OR PRETEACHING WITH INHIBITOR IN 9177 06:55:26,120 --> 06:55:28,920 ALL OF THE MODELS WHAT SHE FOUND 9178 06:55:28,920 --> 06:55:33,960 IS THAT ACTUALLY IS THE DRUG 9179 06:55:33,960 --> 06:55:36,040 DESTROYS OR IS DEPLETING 9180 06:55:36,040 --> 06:55:37,960 MACROPHAGES THAT IS INSTRUMENTAL 9181 06:55:37,960 --> 06:55:42,080 TO FUNCTIONS IN THIS MODEL AND 9182 06:55:42,080 --> 06:55:43,560 THEREFORE I STRONGLY BELIEVE 9183 06:55:43,560 --> 06:55:47,000 THAT CAR T-CELLS MIGHT REQUIRE 9184 06:55:47,000 --> 06:55:48,920 SUPPORT FROM IMMUNE CELLS AND I 9185 06:55:48,920 --> 06:55:52,320 THINK THAT IS IF YOU NOW LOOK AT 9186 06:55:52,320 --> 06:55:53,720 CHECKPOINT WORLD THAT IS 9187 06:55:53,720 --> 06:55:57,480 ACTUALLY WELL ESTABLISHED FOR 9188 06:55:57,480 --> 06:55:59,480 INSTANCE IN COLON CANCER NICK 9189 06:55:59,480 --> 06:56:03,560 PUBLISHED THAT AND CALLS IT 9190 06:56:03,560 --> 06:56:05,560 IMMUNITY HUB AND MYELOID CELLS 9191 06:56:05,560 --> 06:56:07,920 INTERACT IN T-CELLS AND PATIENTS 9192 06:56:07,920 --> 06:56:10,560 THAT HAVE IMMUNITY HUBS ARE 9193 06:56:10,560 --> 06:56:13,680 SENSITIVE TO CHECK POINTS. 9194 06:56:13,680 --> 06:56:18,320 IN CONCLUSION TO MAKE T-CELLS 9195 06:56:18,320 --> 06:56:19,520 BROAD APPLICATOR WE HAVE TO HAVE 9196 06:56:19,520 --> 06:56:22,920 A BETTER UNDERSTANDING OF CAR 9197 06:56:22,920 --> 06:56:25,640 T-CELL BUY OL IN HUMANS AND 9198 06:56:25,640 --> 06:56:28,800 RELEVANT PRECLINICAL MODELS 9199 06:56:28,800 --> 06:56:30,960 TARGETING MULTIPLE ANCONTINUALEN 9200 06:56:30,960 --> 06:56:33,720 AND DO THESE CELLS BEYOND TARGET 9201 06:56:33,720 --> 06:56:35,760 SPECIFICITY AND WE HAVE TO 9202 06:56:35,760 --> 06:56:39,240 DEVELOP EVIDENCE-BASED 9203 06:56:39,240 --> 06:56:41,320 COMBINOTORY THERAPY AND SPEAKERS 9204 06:56:41,320 --> 06:56:43,760 MENTIONING IN SYMPOSIUM THERE IS 9205 06:56:43,760 --> 06:56:47,160 A NEED TO ADJUST REGULATORY 9206 06:56:47,160 --> 06:56:49,280 REQUIREMENTS AND WITH THAT I 9207 06:56:49,280 --> 06:56:53,080 WANT TO THANK ST. JUDE AND MY 9208 06:56:53,080 --> 06:56:54,720 TEAM WHICH OVER THE LAST FIVE 9209 06:56:54,720 --> 06:56:56,800 YEARS I WOULD SAY REALLY HAVE 9210 06:56:56,800 --> 06:57:00,040 BUILT A GOOD TRANSLATIONAL CELL 9211 06:57:00,040 --> 06:57:01,640 THERAPY PROGRAM FOR CHILDREN 9212 06:57:01,640 --> 06:57:05,840 WITH PEDIATRIC CANCER. THANKS 9213 06:57:05,840 --> 06:57:06,920 SO MUCH. 9214 06:57:06,920 --> 06:57:08,080 >> [APPLAUSE]. 9215 06:57:08,080 --> 06:57:11,160 >> OKAY. THANK YOU, STEVE. I 9216 06:57:11,160 --> 06:57:13,240 HAVE THE PRIVILEGE INTRODUCING 9217 06:57:13,240 --> 06:57:15,400 THE LAST SPEAKER OF THE DAY LISA 9218 06:57:15,400 --> 06:57:17,640 WARD THAT YOU WILL SEE VERY SOON 9219 06:57:17,640 --> 06:57:21,600 IS A WOMAN OF COMPASSION AND 9220 06:57:21,600 --> 06:57:24,400 AMAZING ENERGY AND WOMAN OF 9221 06:57:24,400 --> 06:57:25,840 ACTION. SHE IS MOTHER OF BROOK 9222 06:57:25,840 --> 06:57:30,120 AND BLAKE AND LOVING ATTENTIVE 9223 06:57:30,120 --> 06:57:31,480 SUPPORTIVE MOTHER OF JAYS WARD 9224 06:57:31,480 --> 06:57:34,560 WHO CAME TO ASK FOR TREATMENT OF 9225 06:57:34,560 --> 06:57:41,360 -- WITH GD2 T-CELL THERAPY. I 9226 06:57:41,360 --> 06:57:42,760 WALKED INTO JAYS'S ROOM ONE 9227 06:57:42,760 --> 06:57:45,640 AFTERNOON HE WAS LYING IN BED 9228 06:57:45,640 --> 06:57:50,560 WITH A DOLL HE WAS PROBABLY THE 9229 06:57:50,560 --> 06:57:55,240 COOLEST ANLER ANYBODY EVER MET I 9230 06:57:55,240 --> 06:58:00,960 SAID WHY THE DOLL DID HE HE WAS 9231 06:58:00,960 --> 06:58:04,040 MAKING A VIDEO OR DEMO WHAT IT 9232 06:58:04,040 --> 06:58:07,840 WAS LIKE TO HAVE OMIA ACCESSED 9233 06:58:07,840 --> 06:58:09,880 SO YOUNG CHILDREN COMING ON 9234 06:58:09,880 --> 06:58:12,320 TRIAL WOULDN'T BE AFRAID -- 9235 06:58:12,320 --> 06:58:14,400 MAKING THE PANEL EASIER FOR 9236 06:58:14,400 --> 06:58:16,200 OTHERS IN SAME HOSPITAL BED IS 9237 06:58:16,200 --> 06:58:17,600 WHERE THIS SORT OF ORGANIZATION 9238 06:58:17,600 --> 06:58:19,440 EMERGED THAT WE WILL HEAR ABOUT 9239 06:58:19,440 --> 06:58:22,800 FROM LISA BASICALLY TO CARRY 9240 06:58:22,800 --> 06:58:24,680 DIPG COMMUNITY AND THE OTHER 9241 06:58:24,680 --> 06:58:27,080 BRIEF ANECDOTE IS ABOUT THE 9242 06:58:27,080 --> 06:58:31,440 TRIAL AND AS WE HEARD FROM ROBBY 9243 06:58:31,440 --> 06:58:35,840 INTENT WAS TO GIVE ONE DOSE OF 9244 06:58:35,840 --> 06:58:40,280 -- WE SAW PATIENTS EFFICACY 9245 06:58:40,280 --> 06:58:42,520 ABOUT THESE PERSISTING AMENDING 9246 06:58:42,520 --> 06:58:45,680 TRIAL TO GIVE MULTIPLE DOSES 9247 06:58:45,680 --> 06:58:50,520 DIRECTLY INTO VENTRICLES JAYS 9248 06:58:50,520 --> 06:58:55,400 WAS PATIENT NO. 2 ON TRIAL -- 9249 06:58:55,400 --> 06:58:58,280 AND AS WE HEARD FROM PATRICK IT 9250 06:58:58,280 --> 06:59:01,440 IS NOT EASY TO BE PATIENT NO. 1 9251 06:59:01,440 --> 06:59:05,760 AND EMILY WHITEHEADS WITH NEXT 9252 06:59:05,760 --> 06:59:08,720 GENERATION CARS AND JAYS HAD 9253 06:59:08,720 --> 06:59:10,440 COURAGE AND TO SORT OF MOVE THE 9254 06:59:10,440 --> 06:59:14,280 FIELD FORWARD. LET'S HEAR FROM 9255 06:59:14,280 --> 06:59:15,400 LISA. THANK YOU. 9256 06:59:15,400 --> 06:59:25,720 >> [INDISCERNIBLE]. 9257 06:59:33,000 --> 06:59:35,760 >> UNDERSTAND THIS MOMENT IS 9258 06:59:35,760 --> 06:59:37,560 EASY AND UNDERSTAND 9259 06:59:37,560 --> 06:59:40,320 [INDISCERNIBLE] TOGETHER. 9260 06:59:40,320 --> 06:59:42,200 HELPING FOUNDATION 9261 06:59:42,200 --> 06:59:44,280 [INDISCERNIBLE] IN MY LIFETIME. 9262 06:59:44,280 --> 06:59:48,440 DAILY DIPG FIGHTS TO TAKE MY 9263 06:59:48,440 --> 06:59:50,120 SIGHT, MY VOICE, MY MOBILITY, 9264 06:59:50,120 --> 06:59:55,080 AND FINALLY MY LIFE. 9265 06:59:55,080 --> 06:59:58,000 [INDISCERNIBLE] DOESN'T KNOW WHO 9266 06:59:58,000 --> 07:00:02,840 IT IS MESSING WITH. 9267 07:00:02,840 --> 07:00:06,480 [INDISCERNIBLE] STAND UP AND 9268 07:00:06,480 --> 07:00:09,440 STAND BY AND KICK THE HELL OUT 9269 07:00:09,440 --> 07:00:09,960 OF IT. 9270 07:00:09,960 --> 07:00:14,000 >> SO OFTEN IN THE JOURNEY WITH 9271 07:00:14,000 --> 07:00:15,600 CANCER, SOMEONE WOULD SAY TO US, 9272 07:00:15,600 --> 07:00:17,200 I REALLY CAN'T EVEN IMAGINE WHAT 9273 07:00:17,200 --> 07:00:19,360 YOU ARE GOING THROUGH RIGHT NOW. 9274 07:00:19,360 --> 07:00:23,640 AND THAT THEY WERE RIGHT. THEY 9275 07:00:23,640 --> 07:00:28,760 REALLY COULDN'T MANL. THOSE OF 9276 07:00:28,760 --> 07:00:32,440 US IN THE MIDST OF IT CAN'T 9277 07:00:32,440 --> 07:00:36,520 IMAGINE AND IN PLACE NOT SURE 9278 07:00:36,520 --> 07:00:38,560 HOW YOU GOT THERE AND DISEASE 9279 07:00:38,560 --> 07:00:39,680 PROGRESSION THAT DO NOTHING AT 9280 07:00:39,680 --> 07:00:41,200 ALL AND DO NOTHING WITH 9281 07:00:41,200 --> 07:00:43,760 POTENTIAL HARM IS NOT REALLY 9282 07:00:43,760 --> 07:00:45,800 EVEN A CHOICE. 9283 07:00:45,800 --> 07:00:49,800 BUT I CAN'T IMAGINE WHAT YOU AS 9284 07:00:49,800 --> 07:00:51,440 RESEARCHERS OR CLINICIANS OR 9285 07:00:51,440 --> 07:00:53,920 POLICY MAKERS GO THROUGH EITHER. 9286 07:00:53,920 --> 07:00:57,520 I CAN'T IMAGINE THE CONCERN YOU 9287 07:00:57,520 --> 07:01:00,840 FEEL WITH EVERY NEW TRIAL OR 9288 07:01:00,840 --> 07:01:01,880 AMENDMENT TO THE TRIAL. WITH 9289 07:01:01,880 --> 07:01:04,320 EVERY CHOICE THAT DOESN'T PROVE 9290 07:01:04,320 --> 07:01:06,960 TO BE A HOME RUN. I OFTEN THINK 9291 07:01:06,960 --> 07:01:10,560 OF OUR TEAM WHO WE LOVED SO 9292 07:01:10,560 --> 07:01:11,560 MUCH. 9293 07:01:11,560 --> 07:01:13,800 WHO TREATED JACE AND CHILD AFTER 9294 07:01:13,800 --> 07:01:16,200 CHILD WHO HAVE NOW PASSED AWAY. 9295 07:01:16,200 --> 07:01:18,560 EVEN THOUGH THEY ARE ALSO 9296 07:01:18,560 --> 07:01:21,760 TREATING SOME THAT ARE STILL 9297 07:01:21,760 --> 07:01:25,440 RESPONDING SO VERY WELL. 9298 07:01:25,440 --> 07:01:29,080 I KNOW WITH EACH LOSS THERE IS A 9299 07:01:29,080 --> 07:01:31,200 HEAVINESS AND KNOW WITH EACH NEW 9300 07:01:31,200 --> 07:01:32,480 AMENDMENT THAT DID NOT WORKING 9301 07:01:32,480 --> 07:01:34,680 AS PLANNED THERE IS SO MUCH 9302 07:01:34,680 --> 07:01:38,520 CONCERN ABOUT MAKING THE WRONG 9303 07:01:38,520 --> 07:01:38,800 DECISIONS. 9304 07:01:38,800 --> 07:01:40,160 ALL I KNOW TO SHARE WITH YOU IS 9305 07:01:40,160 --> 07:01:43,840 YOU HAVE TO KEEP GOING. WE 9306 07:01:43,840 --> 07:01:45,360 BELIEVE IN YOU. YOU GAVE OUR 9307 07:01:45,360 --> 07:01:48,200 CHILD A CHANCE. YOU ALLOWED OUR 9308 07:01:48,200 --> 07:01:50,360 FAMILY TO LIVE WITH LESS REGRET. 9309 07:01:50,360 --> 07:01:53,360 THERE WERE TIMES TUMORS SHRUNK 9310 07:01:53,360 --> 07:01:55,760 AND SYMPTOMS SUBSIDED AND YOU 9311 07:01:55,760 --> 07:01:58,640 GAVE MORE TIME TO THESE 9312 07:01:58,640 --> 07:01:59,640 FAMILIES. 9313 07:01:59,640 --> 07:02:01,920 YOU EXPLAIN POTENTIAL OUTCOMES, 9314 07:02:01,920 --> 07:02:04,680 GOOD, BAD, AND SO MANY UNKNOWN. 9315 07:02:04,680 --> 07:02:08,200 WE KNOW THAT YOU TRIED WITH THE 9316 07:02:08,200 --> 07:02:10,120 BEST KNOWLEDGE OF THAT DAY TO 9317 07:02:10,120 --> 07:02:13,120 GIVE US MORE TIME, A CHANCE AT A 9318 07:02:13,120 --> 07:02:15,240 CURE, AT THE LIFE WE MANL FOR 9319 07:02:15,240 --> 07:02:19,560 OUR CHILD. FOR THAT, WE ARE 9320 07:02:19,560 --> 07:02:20,880 ETERNALLY GRATEFUL AND FOR THAT 9321 07:02:20,880 --> 07:02:24,320 WE LIVE WITHOUT REGRET. KEEP 9322 07:02:24,320 --> 07:02:26,160 GOING. PUSH THE ENVELOPE. BE 9323 07:02:26,160 --> 07:02:27,800 TRANSPARENT WITH US. 9324 07:02:27,800 --> 07:02:31,640 KNOW THAT EVEN WHEN WE SO WISH 9325 07:02:31,640 --> 07:02:33,240 THAT, THAT CHILD HAD NO EVIDENCE 9326 07:02:33,240 --> 07:02:37,040 OF DISEASE ONE DAY WAS OUR OWN. 9327 07:02:37,040 --> 07:02:39,560 WE CHEER FOR EVERY SINGLE 9328 07:02:39,560 --> 07:02:42,800 VICTORY IN ANY OTHER CHILD AS IF 9329 07:02:42,800 --> 07:02:43,400 IT WAS. 9330 07:02:43,400 --> 07:02:47,480 YOU ARE DOING WHAT 1,000 9331 07:02:47,480 --> 07:02:51,360 DESPERATE PARENTS CANNOT DO. WE 9332 07:02:51,360 --> 07:02:54,920 ARE BEYOND GRATEFUL TO YOU. 9333 07:02:54,920 --> 07:02:56,160 >> THANK YOU SO MUCH FOR WHAT 9334 07:02:56,160 --> 07:02:58,600 YOU DO FOR FAMILIES LIKE MINE. 9335 07:02:58,600 --> 07:03:02,320 I CAN'T DO WHAT YOU DO. 9336 07:03:02,320 --> 07:03:05,000 SO, WHY AM I HERE? 9337 07:03:05,000 --> 07:03:06,920 I HAVE LIVED A PORTION OF THE 9338 07:03:06,920 --> 07:03:08,600 SAME EVOLUTION YOU HAVE SPENT 9339 07:03:08,600 --> 07:03:10,280 YOUR LIFE'S WORK ON FROM A 9340 07:03:10,280 --> 07:03:13,480 DIFFERENT ANGLE. SO, JACE'S 9341 07:03:13,480 --> 07:03:16,520 BATTLE WITH DIPG IS DEFINED IN 9342 07:03:16,520 --> 07:03:19,240 MY MIND BY THREE MOMENTS IN TIME 9343 07:03:19,240 --> 07:03:22,200 THAT ARE SEERED INTO MY 9344 07:03:22,200 --> 07:03:23,200 EVERY-DAY LIVING. 9345 07:03:23,200 --> 07:03:26,400 MAY 17TH, 2019, I STOOD WITH 9346 07:03:26,400 --> 07:03:30,440 JACE IN A SMALL OFFICE IN KANSAS 9347 07:03:30,440 --> 07:03:34,000 CITY. THE WORDS INOPERABLE, 9348 07:03:34,000 --> 07:03:35,920 MALIGNANT, AGGRESSIVE FLOODED 9349 07:03:35,920 --> 07:03:39,240 THE ROOM. NO TREATMENT BUT 9350 07:03:39,240 --> 07:03:40,320 RADIATION. IT WILL KILL YOU. 9351 07:03:40,320 --> 07:03:42,240 THERE IS NO TREATMENT. GO HOME 9352 07:03:42,240 --> 07:03:45,360 AND MAKE MEMORIES. 9353 07:03:45,360 --> 07:03:49,480 JACE RESPONDED, HOW LONG DO I 9354 07:03:49,480 --> 07:03:50,800 HAVE? THE DOCTOR WITH THE 9355 07:03:50,800 --> 07:03:52,920 KINDEST EYES LOOKED INTO MINE 9356 07:03:52,920 --> 07:03:56,240 AND SAID, NO, NO, NO. I'M NOT 9357 07:03:56,240 --> 07:03:59,720 AFRAID TO DIE. I WANT TO KNOW 9358 07:03:59,720 --> 07:04:01,480 HOW LONG I HAVE TO MAKE AN 9359 07:04:01,480 --> 07:04:04,960 IMPACT BEFORE I DO. I NODDED 9360 07:04:04,960 --> 07:04:06,640 AND DOCTOR SAID 6 TO 9 MONTHS. 9361 07:04:06,640 --> 07:04:11,480 HE WAS 20 YEARS OLD. AUGUST 20, 9362 07:04:11,480 --> 07:04:14,800 2020, A ZOOM CALL WITH STANFORD 9363 07:04:14,800 --> 07:04:16,720 BRAND NEW CAR T-CELL TREATMENT 9364 07:04:16,720 --> 07:04:18,440 PATIENT NO. 2 WAS BEING OFFERED 9365 07:04:18,440 --> 07:04:21,120 TO JACE AND NOT MUCH THEY COULD 9366 07:04:21,120 --> 07:04:22,680 TELL US ABOUT PATIENT NO. 1 AT 9367 07:04:22,680 --> 07:04:24,800 ALL. THIS IS A TRIAL THAT 9368 07:04:24,800 --> 07:04:29,240 SEEMED TO WORK IN MOST MICE. 9369 07:04:29,240 --> 07:04:32,080 IT COULD CURE HIM, IT COULD KILL 9370 07:04:32,080 --> 07:04:33,960 HIM, IT COULD DO SOMETHING 9371 07:04:33,960 --> 07:04:35,000 IN-BETWEEN. THEY WOULD DO 9372 07:04:35,000 --> 07:04:37,840 EVERYTHING THEY COULD TO HANTDLE 9373 07:04:37,840 --> 07:04:40,120 THE SIDE-EFFECTS. 9374 07:04:40,120 --> 07:04:41,720 THEY HAD GONE OVER EVERYTHING 9375 07:04:41,720 --> 07:04:43,600 THEY COULD POSSIBLY THINK OF. 9376 07:04:43,600 --> 07:04:47,120 THERE WAS A LOT OF UNKNOWNS. 9377 07:04:47,120 --> 07:04:49,440 AND JACE KNEW WHAT HE WANTED TO 9378 07:04:49,440 --> 07:04:54,240 DO AT THE END OF THE CALL. 9379 07:04:54,240 --> 07:04:57,880 BUT, HE CALLED AN AD HOC 9380 07:04:57,880 --> 07:04:59,280 NATIONAL TUMOR BOARD OF 6 9381 07:04:59,280 --> 07:05:00,560 DOCTORS THEY MET ALONG THE WAY 9382 07:05:00,560 --> 07:05:03,000 AND ASKED IF HE WOULD JUMP ON A 9383 07:05:03,000 --> 07:05:04,520 ZOOM CALL THE NEXT DAY AND HE 9384 07:05:04,520 --> 07:05:07,160 LINE THE OUT GENOMICS AND 9385 07:05:07,160 --> 07:05:09,280 IMAGING AND CLINICAL RECORDS AND 9386 07:05:09,280 --> 07:05:15,640 HE ASKED: WHAT WOULD THEY DO IF 9387 07:05:15,640 --> 07:05:25,120 HE WAS THEIR CHILD? THIS IS A 9388 07:05:25,120 --> 07:05:26,480 HARD DECISION TO MAKE WE CAN'T 9389 07:05:26,480 --> 07:05:28,480 MAKE FOR YOU. WE WILL TELL YOU 9390 07:05:28,480 --> 07:05:31,040 THIS IS PROBABLY THE MOST 9391 07:05:31,040 --> 07:05:31,960 PROMISING THERAPY WE JUST CAN'T 9392 07:05:31,960 --> 07:05:35,320 TELL YOU IF IT WILL WORK. 9393 07:05:35,320 --> 07:05:36,480 DECISION HAD BEEN MADE. 9394 07:05:36,480 --> 07:05:38,360 HE WAS GOING FORWARD. 9395 07:05:38,360 --> 07:05:41,840 I'M HAVING A LITTLE TROUBLE WITH 9396 07:05:41,840 --> 07:05:43,080 MY SLIDE. 9397 07:05:43,080 --> 07:05:47,280 AM I HITTING THE WRONG BUTTON? 9398 07:05:47,280 --> 07:05:49,760 I'M SORRY I WILL KEEP GOING. 9399 07:05:49,760 --> 07:05:52,040 IT IS LATE IN THE DAY. 9400 07:05:52,040 --> 07:05:53,880 >> THANK YOU. SHOWING UP HERE 9401 07:05:53,880 --> 07:05:54,760 FOR A MOMENT. 9402 07:05:54,760 --> 07:05:55,880 >> I KNOW. 9403 07:05:55,880 --> 07:05:57,680 >> NOT CONNECTING. 9404 07:05:57,680 --> 07:05:59,040 >> OKAY. 9405 07:05:59,040 --> 07:06:01,560 >> HE SAID I'M GOING FOR IT. IT 9406 07:06:01,560 --> 07:06:03,360 HAS A CHANCE TO CURE ME. THERE 9407 07:06:03,360 --> 07:06:04,840 IS NOTHING ELSE THAT DOES. WE 9408 07:06:04,840 --> 07:06:08,320 KNOW WHAT HAPPENS IF I DO 9409 07:06:08,320 --> 07:06:10,160 NOTHING. AND IF IT DOESN'T, 9410 07:06:10,160 --> 07:06:11,800 THEY WILL LEARN LOTS FROM ME. 9411 07:06:11,800 --> 07:06:14,560 I'M OLDER AND I CAN EXPLAIN 9412 07:06:14,560 --> 07:06:14,800 THINGS. 9413 07:06:14,800 --> 07:06:16,400 MOM, COULD YOU IMAGINE WHAT A 9414 07:06:16,400 --> 07:06:18,560 DAD OF A 5 YEAR OLD WOULD GO 9415 07:06:18,560 --> 07:06:19,400 THROUGH IF THEY PICK THIS 9416 07:06:19,400 --> 07:06:21,480 THERAPY AND IT KILLS THEM 9417 07:06:21,480 --> 07:06:22,000 IMMEDIATELY? 9418 07:06:22,000 --> 07:06:23,920 CAN YOU EVEN MANL WHAT IT WOULD 9419 07:06:23,920 --> 07:06:28,680 FEEL LIKE WHEN I COULD GO FIRST? 9420 07:06:28,680 --> 07:06:31,320 AND HE WAS PROUD OF THAT 9421 07:06:31,320 --> 07:06:31,840 DECISION. 9422 07:06:31,840 --> 07:06:34,000 THE LAST MOMENT THAT IS SEERED 9423 07:06:34,000 --> 07:06:37,520 INTO MY BRAIN IS JULY SECOND, 9424 07:06:37,520 --> 07:06:41,680 2021. FOR TWO DAYS WE WERE 9425 07:06:41,680 --> 07:06:44,200 UNSURE WHETHER SOME ONSET OF 9426 07:06:44,200 --> 07:06:46,200 SYMPTOMS BACK HOME IN ST. LOUIS 9427 07:06:46,200 --> 07:06:49,360 AREA WERE THE CAUSE OF THE CAR 9428 07:06:49,360 --> 07:06:52,040 T-CELLS RAMPING UP OR SOMETHING 9429 07:06:52,040 --> 07:06:53,480 DIFFERENT. HE WASN'T STABLE 9430 07:06:53,480 --> 07:06:56,200 ENOUGH TO DO AN MRI. 9431 07:06:56,200 --> 07:07:00,600 HE HAD SEVERE HEADACHES AND NO 9432 07:07:00,600 --> 07:07:02,560 LONGER COULD SPEAK AND NO 9433 07:07:02,560 --> 07:07:04,640 MOBILITY AND HIS HANDS COULDN'T 9434 07:07:04,640 --> 07:07:05,840 WORK. HE COULD STILL SPELL. 9435 07:07:05,840 --> 07:07:07,560 THAT IS HOW WE COMMUNICATED. 9436 07:07:07,560 --> 07:07:09,720 DOES IT START WITH A THROUGH M 9437 07:07:09,720 --> 07:07:12,920 OR M THROUGH Z? A, B, C, D. 9438 07:07:12,920 --> 07:07:15,080 STARTS WITH D. HE AND I WERE 9439 07:07:15,080 --> 07:07:17,040 GREAT SPELLERS AND DAD WASN'T. 9440 07:07:17,040 --> 07:07:18,840 THAT WAS THE PROBLEM. HE KNEW 9441 07:07:18,840 --> 07:07:20,200 WHAT HE WANTED. 9442 07:07:20,200 --> 07:07:24,280 AFTER THE MRI WHEN STANFORD TEAM 9443 07:07:24,280 --> 07:07:27,360 WAS CLINGING SO CLOSE TO US FROM 9444 07:07:27,360 --> 07:07:29,000 AFAR, WE KNEW THERE WAS NOTHING 9445 07:07:29,000 --> 07:07:31,080 MORE WE COULD DO. NONE OF THE 9446 07:07:31,080 --> 07:07:32,760 ABILITIES WOULD EVER RETURN. IT 9447 07:07:32,760 --> 07:07:34,680 WAS PROBABLY THE HARDEST THING I 9448 07:07:34,680 --> 07:07:36,560 HAVE EVER DONE TO LEAN INTO HIM 9449 07:07:36,560 --> 07:07:41,200 AND TELL HIM HOW MUCH I LOVED 9450 07:07:41,200 --> 07:07:42,520 HIM. 9451 07:07:42,520 --> 07:07:45,200 AND TO WATCH HIS EYES AND TO 9452 07:07:45,200 --> 07:07:47,640 TELL HIM WE HAD COME TO THE END 9453 07:07:47,640 --> 07:07:50,240 OF THE FIGHT, 25 MONTHS. THERE 9454 07:07:50,240 --> 07:07:52,640 WAS NOTHING MORE THAT WE COULD 9455 07:07:52,640 --> 07:07:53,400 DO. 9456 07:07:53,400 --> 07:07:57,600 AND MY EYES WERE FILLED WITH 9457 07:07:57,600 --> 07:07:59,160 TEARS. HIS EYES WERE FILLED 9458 07:07:59,160 --> 07:08:01,800 WITH SOMETHING ELSE. THEY WERE 9459 07:08:01,800 --> 07:08:06,240 FILLED WITH FURY AND FILLED WITH 9460 07:08:06,240 --> 07:08:08,600 THAT DESIRE TO KEEP FIGHTING AND 9461 07:08:08,600 --> 07:08:11,280 BATTLING EVEN THOUGH HIS BODY 9462 07:08:11,280 --> 07:08:13,080 HAD LONG WARN OUT AND WAS 9463 07:08:13,080 --> 07:08:15,080 FUELING THE SAME THING THAT 9464 07:08:15,080 --> 07:08:16,880 FUELS YOUR WORK. THERE HAS TO 9465 07:08:16,880 --> 07:08:19,480 BE AN ANSWER. HE DID NOT WANT 9466 07:08:19,480 --> 07:08:22,720 THIS TUMOR TO WIN. AS OUR EYES 9467 07:08:22,720 --> 07:08:25,480 LOCK THE, THAT FURY TRANSFERRED 9468 07:08:25,480 --> 07:08:27,880 TO ME AND CONTINUES TO DRIVE OUR 9469 07:08:27,880 --> 07:08:28,480 WORK. 9470 07:08:28,480 --> 07:08:31,000 YOU KNOW, JACE HAD GREAT FAITH. 9471 07:08:31,000 --> 07:08:34,160 HE WAS NOT AFRAID WHAT HIS NEXT 9472 07:08:34,160 --> 07:08:37,040 CHAPTER WOULD BE. HE DID NOT 9473 07:08:37,040 --> 07:08:39,080 WANT TO GIVE UP FOR THOSE LITTLE 9474 07:08:39,080 --> 07:08:42,640 ONES WHO HAD NOT FINISHED 9475 07:08:42,640 --> 07:08:45,400 KINDERGARTEN OR PROM OR PLAYED 9476 07:08:45,400 --> 07:08:46,960 FOOTBALL UNDER THE LIGHTS. HE 9477 07:08:46,960 --> 07:08:48,920 WANTED TO BE THERE WHEN HE WAS 9478 07:08:48,920 --> 07:08:52,120 ABLE TO RING THE BELL AND MORE 9479 07:08:52,120 --> 07:08:53,240 IMPORTANTLY WATCH ALL OF THE 9480 07:08:53,240 --> 07:08:55,560 OTHER KIDS HE HAD MET ALONG THE 9481 07:08:55,560 --> 07:08:58,040 WAY. HE WAS SO, SO DETERMINED. 9482 07:08:58,040 --> 07:09:00,720 YOU KNOW, SINCE THEN WE HAVE MET 9483 07:09:00,720 --> 07:09:04,720 -- DID WE HAVE ANY LUCK ON THE 9484 07:09:04,720 --> 07:09:05,720 SLIDES? 9485 07:09:05,720 --> 07:09:10,040 THE SLIDES DIDN'T COME THROUGH. 9486 07:09:10,040 --> 07:09:12,480 OKAY. OKAY. PERFECT. THAT IS 9487 07:09:12,480 --> 07:09:15,080 PERFECT. SO, ALONG THE WAY WE 9488 07:09:15,080 --> 07:09:18,600 HAVE MET 361 FAMILIES. 9489 07:09:18,600 --> 07:09:21,680 DIPG IS NOT RARE. 9490 07:09:21,680 --> 07:09:26,320 AND AS OF LAST NIGHT, NO. 362 BY 9491 07:09:26,320 --> 07:09:28,920 PHONE. IT IS ALWAYS THE SAME 9492 07:09:28,920 --> 07:09:30,280 PHONE CALL. 9493 07:09:30,280 --> 07:09:32,080 MY CHILD WAS JUST DIAGNOSED. I 9494 07:09:32,080 --> 07:09:33,840 HEARD YOU ARE A REALLY GOOD 9495 07:09:33,840 --> 07:09:37,360 PERSON TO TALK TO ABOUT THE 9496 07:09:37,360 --> 07:09:39,200 OPTIONS. 9497 07:09:39,200 --> 07:09:44,440 I JUST CAN'T IMAGINE THAT THERE 9498 07:09:44,440 --> 07:09:46,480 IS NOTHING THAT WE CAN DO. WE 9499 07:09:46,480 --> 07:09:48,600 GO THROUGH THOSE. YOU CAN 9500 07:09:48,600 --> 07:09:50,120 IMAGINE THAT THE ANSWER IS LET'S 9501 07:09:50,120 --> 07:09:52,080 FIND SOMETHING TO KEEP YOUR 9502 07:09:52,080 --> 07:09:53,760 CHILD STABLE UNTIL WE FIND A 9503 07:09:53,760 --> 07:09:55,160 TREATMENT THAT CAN WORK. TO 9504 07:09:55,160 --> 07:09:57,040 THINK OF ANYTHING ELSE IN THOSE 9505 07:09:57,040 --> 07:10:00,760 EARLY MOMENTS IS JUST THE 9506 07:10:00,760 --> 07:10:02,920 UNTHINKABLE FOR ANY OF US. 9507 07:10:02,920 --> 07:10:05,800 YOU ARE DOING WHAT WE CAN'T DO. 9508 07:10:05,800 --> 07:10:09,640 WE ARE SO, SO GRATEFUL. YOU ARE 9509 07:10:09,640 --> 07:10:11,000 PUSHING THAT EDGE OF SCIENCE. 9510 07:10:11,000 --> 07:10:13,080 AS FAMILIES, WE ARE PUSHING 9511 07:10:13,080 --> 07:10:13,920 RIGHT WITH YOU. 9512 07:10:13,920 --> 07:10:16,320 I KNOW THAT MANY OF YOU, 9513 07:10:16,320 --> 07:10:18,360 PROBABLY ALL OF YOU, TOOK AN 9514 07:10:18,360 --> 07:10:20,400 OATH TO DO NO HARM. 9515 07:10:20,400 --> 07:10:24,280 IN A CANCER-LIKE DIPG TO DO 9516 07:10:24,280 --> 07:10:26,640 NOTHING IS TO DO HARM. 9517 07:10:26,640 --> 07:10:29,160 WE KNOW WHAT THAT TRAJECTORY 9518 07:10:29,160 --> 07:10:31,520 LOOKS LIKE. TO BE TRANSPARENT, 9519 07:10:31,520 --> 07:10:33,440 TO SAY HERE IS WHERE WE ARE AND 9520 07:10:33,440 --> 07:10:35,800 WE KNOW WE HAVE TO GET HERE AND 9521 07:10:35,800 --> 07:10:37,960 WE ARE NOT EXACTLY SURE WHERE 9522 07:10:37,960 --> 07:10:38,560 THE ROAD GOES. 9523 07:10:38,560 --> 07:10:40,800 IF YOU WANT TO WALK WITH US, 9524 07:10:40,800 --> 07:10:43,880 THERE IS ROOM. 9525 07:10:43,880 --> 07:10:46,200 THAT IS TO DO SOMETHING. 9526 07:10:46,200 --> 07:10:51,040 YOU MAY BE TIRED AND WARN. I 9527 07:10:51,040 --> 07:10:54,040 KNOW THAT EVERY ONE OF YOU IS 9528 07:10:54,040 --> 07:10:56,320 EVERY BIT AS DETERMINED AND 9529 07:10:56,320 --> 07:10:57,280 RESILIENT AS LITTLE CHILDREN 9530 07:10:57,280 --> 07:11:00,720 THAT YOU SAW IN THE VIDEO. I 9531 07:11:00,720 --> 07:11:02,520 INSTEAD TO SUGGEST TODAY THAT 9532 07:11:02,520 --> 07:11:04,480 YOU USE THE FAMILIES IN THE 9533 07:11:04,480 --> 07:11:05,760 FIGHT WITH YOU. 9534 07:11:05,760 --> 07:11:08,720 USE THEM IN YOUR ARSENAL TO WIN 9535 07:11:08,720 --> 07:11:09,960 THIS BATTLE. 9536 07:11:09,960 --> 07:11:12,760 YOU SEE, WE CAN NAVIGATE 9537 07:11:12,760 --> 07:11:15,600 PATIENCE YOUR WAY. IF YOU KEEP 9538 07:11:15,600 --> 07:11:18,200 US UP TO DATE ON THE WINS AND 9539 07:11:18,200 --> 07:11:19,680 ADJUSTMENTS IN YOUR WORK. I 9540 07:11:19,680 --> 07:11:21,360 KNOW THAT THERE IS A LOT OF 9541 07:11:21,360 --> 07:11:22,600 INFORMATION THAT YOU ARE KEEPING 9542 07:11:22,600 --> 07:11:25,800 TO PUBLISH. THAT IS TOTALLY 9543 07:11:25,800 --> 07:11:26,160 UNDERSTANDABLE. 9544 07:11:26,160 --> 07:11:28,360 THERE ARE SOME THINGS YOU CAN 9545 07:11:28,360 --> 07:11:31,000 TELL US THAT HELPS US TO ADVISE 9546 07:11:31,000 --> 07:11:36,520 IN A WAY THAT DOES NO THE FEEL 9547 07:11:36,520 --> 07:11:38,680 COMPLETELY LIKE BLINDED RUSSIAN 9548 07:11:38,680 --> 07:11:39,920 ROULETTE WITH YOUR CHILD. LET 9549 07:11:39,920 --> 07:11:42,760 US AMPLIFY TO THE PATIENT 9550 07:11:42,760 --> 07:11:44,960 COMMUNITY HOPE IN ACTION. IN A 9551 07:11:44,960 --> 07:11:46,880 REAL PARENT TO PARENT WAY. 9552 07:11:46,880 --> 07:11:48,800 BECAUSE THEY ARE LOOKING FOR 9553 07:11:48,800 --> 07:11:51,320 THAT ON FACEBOOK ANYWAY. 9554 07:11:51,320 --> 07:11:56,200 HELP PARENTS IN YOUR COMMUNITY 9555 07:11:56,200 --> 07:11:56,960 BE INFORMED WITH INFORMATION 9556 07:11:56,960 --> 07:11:58,600 THAT THEY ARE SHARING. 9557 07:11:58,600 --> 07:12:00,840 ASK US FOR FEEDBACK. 9558 07:12:00,840 --> 07:12:04,000 ASK US WHAT THE FACEBOOK AND 9559 07:12:04,000 --> 07:12:06,320 INSTAGRAM COMMUNITY IS SAYING 9560 07:12:06,320 --> 07:12:09,440 ABOUT YOUR CAR T-CELL TRIALS OR 9561 07:12:09,440 --> 07:12:11,480 ADVANCED THERAPY TRIALS. THERE 9562 07:12:11,480 --> 07:12:14,200 IS ALWAYS OPINIONS OUT THERE. 9563 07:12:14,200 --> 07:12:16,840 ASK US WHAT NEW SUPPLEMENT OR 9564 07:12:16,840 --> 07:12:18,360 THERAPY IS THE NEXT THING TO 9565 07:12:18,360 --> 07:12:19,760 MAKE ROUNDS AND THAT SOMEBODY IS 9566 07:12:19,760 --> 07:12:21,680 TAKING NOT TELLING YOU IN YOUR 9567 07:12:21,680 --> 07:12:27,600 TRIAL. I'M AN EDUCATED PERSON I 9568 07:12:27,600 --> 07:12:30,160 WILL ADMIT THERE WAS A TIME I 9569 07:12:30,160 --> 07:12:32,520 STOOD IN A PET FILE TO LOOK FOR 9570 07:12:32,520 --> 07:12:34,040 DE-WORMER. MY SON CALLED AND 9571 07:12:34,040 --> 07:12:36,840 SAID WHAT ARE YOU DOING? 9572 07:12:36,840 --> 07:12:40,240 LOOKING AT DE-WORMER. DOES OUR 9573 07:12:40,240 --> 07:12:42,760 DOG HAVE WORMS? NO. I BET IT 9574 07:12:42,760 --> 07:12:44,320 COULD HELP YOU WITH YOUR CANCER. 9575 07:12:44,320 --> 07:12:46,480 GET OUT OF THE AISLE. YOU ARE 9576 07:12:46,480 --> 07:12:48,320 NOT A DOCTOR AND WILL NEVER BE 9577 07:12:48,320 --> 07:12:52,400 AND TRUST THOSE THAT ARES. I 9578 07:12:52,400 --> 07:12:54,120 UNDERSTAND THE PLIGHT OF PARENTS 9579 07:12:54,120 --> 07:12:57,120 AND ALLOW US TO HELP IF YOUR 9580 07:12:57,120 --> 07:12:58,600 PATIENTS NEED FINANCIAL OR 9581 07:12:58,600 --> 07:13:00,000 EMOTIONAL OR PALLIATIVE SUPPORT 9582 07:13:00,000 --> 07:13:03,400 THAT IS NOT ABLE TO BE REACHED 9583 07:13:03,400 --> 07:13:05,240 QUICKSLY IN YOUR INSTITUTIONS. 9584 07:13:05,240 --> 07:13:07,240 WE HAD NUMBERS OF TIMES THAT 9585 07:13:07,240 --> 07:13:08,840 PATIENTS NEEDED TO GET HOME FOR 9586 07:13:08,840 --> 07:13:13,440 A TRIAL ACROSS THE COUNTRY FOR 9587 07:13:13,440 --> 07:13:16,080 PALLIATIVE CARE OR THERE IS NO 9588 07:13:16,080 --> 07:13:17,840 MONEY TO BURY A CHILD OR GET 9589 07:13:17,840 --> 07:13:19,520 THEM TO THE TRIAL OR BRING THEIR 9590 07:13:19,520 --> 07:13:21,360 DAD TO THE TRIAL OR BABY BROTHER 9591 07:13:21,360 --> 07:13:23,240 TO THE TRIAL. THAT IS THE PLACE 9592 07:13:23,240 --> 07:13:25,840 THAT WE CAN HELP. IN SOMETHING 9593 07:13:25,840 --> 07:13:28,480 THAT MOVES AS QUICKLY AS DIPG 9594 07:13:28,480 --> 07:13:30,240 WHICH IS WHAT I KNOW THE MOST 9595 07:13:30,240 --> 07:13:32,280 ABOUT, WE KNOW WE CAN'T WAIT FOR 9596 07:13:32,280 --> 07:13:34,000 LONG APPLICATIONS AND TIME FOR 9597 07:13:34,000 --> 07:13:36,200 THE SOCIAL WORKER TO MAKE IT TO 9598 07:13:36,200 --> 07:13:38,040 THE ROOM SOME TIME IN THE NEXT 2 9599 07:13:38,040 --> 07:13:42,040 OR 3 WEEKS. 9600 07:13:42,040 --> 07:13:43,680 INSTEAD, USE FAMILY SUPPORT LIKE 9601 07:13:43,680 --> 07:13:45,880 WE HAVE TO MAKE THAT ONE CALL 9602 07:13:45,880 --> 07:13:47,920 AND EXPLAIN THE NEED AND ASK THE 9603 07:13:47,920 --> 07:13:50,480 FAMILY TO CONTACT US. WE WILL 9604 07:13:50,480 --> 07:13:52,040 SEND IT THROUGH VENMO OR FILL 9605 07:13:52,040 --> 07:13:54,120 OUT THE APPLICATION FOR THEM. 9606 07:13:54,120 --> 07:13:55,720 WE WILL HAVE THEM DOCU SIGN IT. 9607 07:13:55,720 --> 07:13:57,640 WE WILL SEND IT ON TO THE 9608 07:13:57,640 --> 07:13:58,960 FOUNDATIONS THAT TRUST US AND WE 9609 07:13:58,960 --> 07:14:01,440 WILL HAVE FUNDS THE NEXT DAY. 9610 07:14:01,440 --> 07:14:04,320 BECAUSE WE KNOW WHAT IT IS LIKE 9611 07:14:04,320 --> 07:14:06,480 TO SIT IN AN EMERGENCY ROOM AND 9612 07:14:06,480 --> 07:14:08,880 WATCH THE NEXT MOTHER NOT HAVE 9613 07:14:08,880 --> 07:14:11,000 ANYTHING TO EAT. BECAUSE SHE 9614 07:14:11,000 --> 07:14:13,160 CAME WITHOUT HER PURSE OR HER 9615 07:14:13,160 --> 07:14:15,560 BANK ACCOUNT IS OVERDRAFT AND 9616 07:14:15,560 --> 07:14:16,720 FOR THE EMERGENCY ROOM DOCTOR TO 9617 07:14:16,720 --> 07:14:20,240 SAY, I'M SORRY WE ONLY SERVE 9618 07:14:20,240 --> 07:14:20,480 PATIENTS. 9619 07:14:20,480 --> 07:14:23,600 WE KNOW WHAT THOSE DAYS FEEL 9620 07:14:23,600 --> 07:14:24,840 LIKE. WE DON'T WANT THAT TO ANY 9621 07:14:24,840 --> 07:14:26,800 OTHER FAMILIES AND WE WANT YOU 9622 07:14:26,800 --> 07:14:30,080 TO DO YOUR JOB THAT WE CAN'T DO. 9623 07:14:30,080 --> 07:14:31,400 SO, DON'T EVER FEEL BAD ABOUT 9624 07:14:31,400 --> 07:14:34,440 ASKING FAMILIES TO HELP DO WHAT 9625 07:14:34,440 --> 07:14:36,760 YOU -- WHAT WE CAN DO. IT IS AN 9626 07:14:36,760 --> 07:14:38,720 HONOR AND IT IS A PRIVILEGE AND 9627 07:14:38,720 --> 07:14:41,160 IT IS A WAY OF CONTINUING THE 9628 07:14:41,160 --> 07:14:43,600 PURPOSE OF OUR CHILD IN THE 9629 07:14:43,600 --> 07:14:46,040 FIGHT. WE KNOW AS WELL AS 9630 07:14:46,040 --> 07:14:47,960 ANYONE WHAT THAT FEELS LIKE. I 9631 07:14:47,960 --> 07:14:50,000 WILL SHARE A COUPLE WINS REAL 9632 07:14:50,000 --> 07:14:51,760 QUICK ALONG THE LINES YOU 9633 07:14:51,760 --> 07:14:55,080 WOULDN'T EXPECT. A MOTHER IN 9634 07:14:55,080 --> 07:14:58,960 CINCINNATI AND CHILD TREATED FOR 9635 07:14:58,960 --> 07:15:01,240 DIPG FOR TWO YEARS REAL WIN IN 9636 07:15:01,240 --> 07:15:05,360 OUR WORLD TWO YEARS THIS CHILD 9637 07:15:05,360 --> 07:15:09,280 ANL 8 AND BELOW BELOW POVERTY 9638 07:15:09,280 --> 07:15:15,200 LINE CLEARLY RECEIVED 2 $25 GAS 9639 07:15:15,200 --> 07:15:17,280 CERTIFICATES AND SHEPHERDS PIE 9640 07:15:17,280 --> 07:15:19,840 FROM NEIGHBOR BEFORE I TOOK 9641 07:15:19,840 --> 07:15:23,040 PHONE CALL WE PROVIDED CHRISTMAS 9642 07:15:23,040 --> 07:15:27,400 AND FILLED PANTRY AND 9643 07:15:27,400 --> 07:15:28,840 REFRIGERATOR AND HOSPICE NURSE 9644 07:15:28,840 --> 07:15:30,560 CAME AND ON HER OWN TIME SHE 9645 07:15:30,560 --> 07:15:32,560 TOOK IT TO A JEWELRY STORE AND 9646 07:15:32,560 --> 07:15:35,960 HAD THE JEWELRY MAKER MAKE A 9647 07:15:35,960 --> 07:15:38,760 RING OF THE FINGER PRINT AND 9648 07:15:38,760 --> 07:15:41,160 PROVIDED CHRISTMAS GIFTS AND 9649 07:15:41,160 --> 07:15:42,840 MOTHERS GOT OUT OF BED AND 9650 07:15:42,840 --> 07:15:43,760 STARTED TO TAKE LESS MEDICATION 9651 07:15:43,760 --> 07:15:47,840 AND STARTED TO RELY LESS ON 9652 07:15:47,840 --> 07:15:49,040 NONPRESCRIPTION ASSISTANCE AND 9653 07:15:49,040 --> 07:15:52,120 TOOK THE LITTLE BOYS CASE TO A 9654 07:15:52,120 --> 07:15:54,440 TUMOR BOARD THAT LED TO 9655 07:15:54,440 --> 07:15:56,360 RE-RADIATION AND ADMISSION INTO 9656 07:15:56,360 --> 07:15:58,560 A NEW TRIAL. SHE TEXTED ME LAST 9657 07:15:58,560 --> 07:16:00,920 WEEK AND SENT ME A PICTURE OF 9658 07:16:00,920 --> 07:16:02,560 THE LITTLE BOY WHOSE COLORING 9659 07:16:02,560 --> 07:16:05,280 FOR THE FIRST TIME IN 20 MONTHS 9660 07:16:05,280 --> 07:16:09,040 AND WAS OUTSIDE PLAYING ON HIS 9661 07:16:09,040 --> 07:16:10,680 SWING SET. 9662 07:16:10,680 --> 07:16:12,360 WE JUST DON'T KNOW; RIGHT? 9663 07:16:12,360 --> 07:16:14,880 WHAT IT TAKES FOR THE NEXT 9664 07:16:14,880 --> 07:16:17,920 PARENT TO TAKE THE NEXT STEP 9665 07:16:17,920 --> 07:16:21,480 WITH THEIR CHILD. WHAT MADE ME 9666 07:16:21,480 --> 07:16:22,240 EVEN HAPPIER WAS THURSDAY SHE 9667 07:16:22,240 --> 07:16:25,240 SENT ME A PICTURE OF SHE AND HER 9668 07:16:25,240 --> 07:16:27,440 SON TAKING A PUPPY THAT THEY 9669 07:16:27,440 --> 07:16:28,920 BREED AND RAISE TO ANOTHER 9670 07:16:28,920 --> 07:16:31,280 LITTLE BOY THAT THEY MET LOCALLY 9671 07:16:31,280 --> 07:16:38,720 ALSO WITH DIPG. SHE WAS HAPPY 9672 07:16:38,720 --> 07:16:40,760 TO PAY IT FORWARD TO THE NEXT 9673 07:16:40,760 --> 07:16:42,520 FAMILY. THAT IS A STORY I WILL 9674 07:16:42,520 --> 07:16:44,920 ALWAYS HANG ON TO. ANOTHER ONE 9675 07:16:44,920 --> 07:16:46,680 IN FLORIDA A YOUNG MOM WHO IS 26 9676 07:16:46,680 --> 07:16:49,160 WHO HAS A 6 AND 8 YEAR OLD AND 6 9677 07:16:49,160 --> 07:16:52,480 YEAR OLD HAS DIPG AND 6 YEAR OLD 9678 07:16:52,480 --> 07:16:55,200 TOOK A TURN DOWNHILL AND NEEDED 9679 07:16:55,200 --> 07:16:56,480 A WHEELCHAIR AT HOSPITAL AND 9680 07:16:56,480 --> 07:16:58,560 MANY OF YOU KNOW PEDIATRIC 9681 07:16:58,560 --> 07:17:00,600 WHEELCHAIR IS NOT SOMETHING YOU 9682 07:17:00,600 --> 07:17:02,000 CAN FIND OVERNIGHT SOMETIMES AND 9683 07:17:02,000 --> 07:17:04,800 WE KNEW A MOTHER WHO HAD ONE AND 9684 07:17:04,800 --> 07:17:06,240 WHOSE SON PASS AD WAY EARLIER 9685 07:17:06,240 --> 07:17:07,880 THIS FALL. I SAID RACHEL IS 9686 07:17:07,880 --> 07:17:11,800 THERE ANY WAY THAT YOU WOULD 9687 07:17:11,800 --> 07:17:15,000 WANT TO LET ELIA'S WHEELCHAIR 9688 07:17:15,000 --> 07:17:16,720 AND MOM IN THE HOSPITAL IN MIAMI 9689 07:17:16,720 --> 07:17:18,760 THAT COULD USE IT AND IF YOU 9690 07:17:18,760 --> 07:17:22,080 WOULDN'T MIND YOU CAN JUST BRING 9691 07:17:22,080 --> 07:17:23,520 IT TO THE HOSPITAL AND THEY WILL 9692 07:17:23,520 --> 07:17:25,360 MAKE SURE IT IS TO THE RIGHT 9693 07:17:25,360 --> 07:17:27,800 ROOM AND I CAN MAKE SURE OF 9694 07:17:27,800 --> 07:17:29,000 ARRANGEMENTS AND SHE SAID THAT 9695 07:17:29,000 --> 07:17:34,440 IS BEST AND NOT READY TO MAKE 9696 07:17:34,440 --> 07:17:36,600 MOMS OR KIDS AND I UNDERSTAND 9697 07:17:36,600 --> 07:17:38,520 AND WHEN SHE GOT THERE I WOULD 9698 07:17:38,520 --> 07:17:40,680 LIKE TO MEET MOM I DID SPENT 9699 07:17:40,680 --> 07:17:42,400 TIME TALKING AND SHE WAS HELPING 9700 07:17:42,400 --> 07:17:44,880 TO PLAN THE 6 YEAR OLD'S 9701 07:17:44,880 --> 07:17:46,800 BIRTHDAY PARTY AND TAKING THEM 9702 07:17:46,800 --> 07:17:49,520 GROCERY SHOPPING ON 26 YEAR OLD 9703 07:17:49,520 --> 07:17:51,880 MOMLE'S CAR BROKE DOWN AND 26 9704 07:17:51,880 --> 07:17:54,360 YEAR OLD'S MOTHER WHO WAS 42 HAD 9705 07:17:54,360 --> 07:17:58,520 AN ANNURISM AND WAS IN ICU FIVE 9706 07:17:58,520 --> 07:18:00,560 DAYS BEFORE PASSING AWAY. DO 9707 07:18:00,560 --> 07:18:03,240 YOU KNOW WHO TOOK CARE OF THE 9708 07:18:03,240 --> 07:18:06,440 KIDS? RACHEL, THE MOM WHO LOST 9709 07:18:06,440 --> 07:18:08,760 HER CHILD IN NOVEMBER. 9710 07:18:08,760 --> 07:18:10,240 THAT IS SOMETHING THAT THEY KNEW 9711 07:18:10,240 --> 07:18:13,720 TO DO. THE 6 YEAR OLD HAD AN NG 9712 07:18:13,720 --> 07:18:16,280 TUBE. SHE SOMETIMES NEEDED 9713 07:18:16,280 --> 07:18:17,920 SUCTION AND WASN'T COMFORTABLE 9714 07:18:17,920 --> 07:18:19,600 LAYING IN EVERY DIRECTION AND 9715 07:18:19,600 --> 07:18:21,320 YOUNG MOM COULDN'T TRUST HER TO 9716 07:18:21,320 --> 07:18:23,400 ANYONE ELSE THAT SHE KNEW. 9717 07:18:23,400 --> 07:18:28,080 RELY ON THE FAMILIES. 9718 07:18:28,080 --> 07:18:29,720 SOMETIMES A HOSPITAL -- A DOCTOR 9719 07:18:29,720 --> 07:18:31,200 OF A HOSPITAL WILL CALL AND SAY 9720 07:18:31,200 --> 07:18:33,760 THERE IS A PATIENT I'M CARING 9721 07:18:33,760 --> 07:18:34,920 FOR THAT DOESN'T KNOW ANYONE 9722 07:18:34,920 --> 07:18:37,880 ELSE WITH DIPG OR DMG. I CAN'T 9723 07:18:37,880 --> 07:18:39,720 TELL THEM THAT THERE IS A 9724 07:18:39,720 --> 07:18:41,640 PATIENT IN THE NEXT ROOM. YOU 9725 07:18:41,640 --> 07:18:43,640 PROBABLY KNOW WHO THAT PATIENT 9726 07:18:43,640 --> 07:18:46,080 IS. IS THERE A WAY THAT IF THEY 9727 07:18:46,080 --> 07:18:47,880 CALL YOU YOU WOULD BEL TO 9728 07:18:47,880 --> 07:18:49,120 CONNECT THEM WITH ANYONE ELSE 9729 07:18:49,120 --> 07:18:52,240 THAT MIGHT BE IN THE AREA? 9730 07:18:52,240 --> 07:18:54,160 ABSOLUTELY. THAT IS HOW THOSE 9731 07:18:54,160 --> 07:18:56,560 FRIENDSHIPS HAVE FORMED AND MORE 9732 07:18:56,560 --> 07:18:57,960 OFTEN THAN NOT WE KNOW FAMILIES 9733 07:18:57,960 --> 07:19:01,080 IN THE AREA THAT WILL PROVIDE A 9734 07:19:01,080 --> 07:19:03,760 MEAL OR A CAR OR PLACE TO STAY 9735 07:19:03,760 --> 07:19:06,080 OVERNIGHT BECAUSE THEY HAVE BEEN 9736 07:19:06,080 --> 07:19:08,200 IN THAT SAME PLACE. WE DON'T 9737 07:19:08,200 --> 07:19:10,960 NEED LOTS AND LOTS OF 9738 07:19:10,960 --> 07:19:12,760 REGULATIONS AND COMPLICATED 9739 07:19:12,760 --> 07:19:15,760 PROGRAMS TO DO THIS. WE JUST 9740 07:19:15,760 --> 07:19:18,040 NEED ONE PARENT TELLING ANOTHER 9741 07:19:18,040 --> 07:19:20,280 ONE WHERE TO FIND HOPE. YOU 9742 07:19:20,280 --> 07:19:22,040 NEED SOMEBODY YOU CAN TRUST AND 9743 07:19:22,040 --> 07:19:24,960 ROOI LIE ON TO ANSWER THOSE 9744 07:19:24,960 --> 07:19:27,280 CALLS WHEN YOU MAKE THEM. 9745 07:19:27,280 --> 07:19:30,760 I CAN ALSO TELL YOU THAT COUNT 9746 07:19:30,760 --> 07:19:33,960 ON US TO BE INFORMED ADVOCATES 9747 07:19:33,960 --> 07:19:36,400 AS YOU CHOOSE TO HELP WITH 9748 07:19:36,400 --> 07:19:39,000 FUNDING RESEARCH OR CHANGES IN 9749 07:19:39,000 --> 07:19:41,200 REGULATION OR SHARING OF TISSUE 9750 07:19:41,200 --> 07:19:43,280 AND DATA. WE KNOW HOW IMPORTANT 9751 07:19:43,280 --> 07:19:44,960 THOSE ARE AND WILL COME AND WE 9752 07:19:44,960 --> 07:19:47,360 WILL HELP WHEN WE CAN. I WILL 9753 07:19:47,360 --> 07:19:49,120 GIVE YOU A GLIMPSE OF WHAT WE 9754 07:19:49,120 --> 07:19:51,200 HAVE DONE IN THE LAST YEAR SO 9755 07:19:51,200 --> 07:20:23,200 YOU CAN KNOW QUICKLY WHAT IS 9756 07:20:23,200 --> 07:20:23,400 POSSIBLE. 9757 07:20:23,400 --> 07:20:25,880 WOULD YOU RELY ON A MOM WHO 9758 07:20:25,880 --> 07:20:28,200 DIDN'T KNOW THEY HAD A PONS FOR 9759 07:20:28,200 --> 07:20:29,840 ADVICE AND THEY SHOULDN'T AND 9760 07:20:29,840 --> 07:20:32,280 WITH HELP OF CHAD AND DIPG AND 9761 07:20:32,280 --> 07:20:36,640 20 OTHER FOUNDATIONS WITH HE 9762 07:20:36,640 --> 07:20:40,560 FUNDED DIPG NAVIGATOR A NURSE 9763 07:20:40,560 --> 07:20:42,560 NAVIGATION SYSTEM THAT PROVIDES 9764 07:20:42,560 --> 07:20:43,840 EDUCATION AND ANSWERS QUESTIONS 9765 07:20:43,840 --> 07:20:44,160 AND HELPS PATIENTS TO FIND 9766 07:20:44,160 --> 07:20:45,680 CENTERS OF EXCELLENCE WITH 9767 07:20:45,680 --> 07:20:47,280 TRIALS THAT STAY UP TO DATE ON 9768 07:20:47,280 --> 07:20:50,400 HOW THE TRIALS COMPASSIONATE USE 9769 07:20:50,400 --> 07:20:52,440 AND ADJUNCTIVE THERAPIES ARE 9770 07:20:52,440 --> 07:20:55,800 GOING AND NOW THERE IS FOUR 9771 07:20:55,800 --> 07:20:57,760 FULL-TIME NURSES THAT THEY 9772 07:20:57,760 --> 07:21:05,160 SERVED 196DIPG DNG PATIENTS 9773 07:21:05,160 --> 07:21:10,200 SINCE MAY AND CAN CASE LLOYD 9774 07:21:10,200 --> 07:21:12,640 CONTINUES TO GROW. WE WENT BACK 9775 07:21:12,640 --> 07:21:14,560 THINKING ABOUT THE AD HOC 2 9776 07:21:14,560 --> 07:21:17,040 BOARD AND HOW MUCH RELIEF IT 9777 07:21:17,040 --> 07:21:18,480 GAVE NOT SCROLLING THROUGH 9778 07:21:18,480 --> 07:21:21,360 CLINICAL TRIALS.GOV TO PICK WHAT 9779 07:21:21,360 --> 07:21:23,480 WAS NEXT FOR JACE. WE PICKED 9780 07:21:23,480 --> 07:21:28,440 THE CREAM OF THE CROP IN THE 9781 07:21:28,440 --> 07:21:32,720 DIPG WORLD AND ACROSS THE 9782 07:21:32,720 --> 07:21:35,200 COUNTRY WOULD YOU DO A ZOOM CALL 9783 07:21:35,200 --> 07:21:36,760 TWICE A MONTH AND PROVIDE 9784 07:21:36,760 --> 07:21:39,960 OPTIONS FOR YOUR PEERS FOR OTHER 9785 07:21:39,960 --> 07:21:42,320 PROVIDERS? NOW A FAMILY 9786 07:21:42,320 --> 07:21:43,560 PROVIDER AND ONE OF THE 9787 07:21:43,560 --> 07:21:44,560 [INDISCERNIBLE] NAVIGATORS CAN 9788 07:21:44,560 --> 07:21:46,240 HELP A PATIENT SIGN UP AND 9789 07:21:46,240 --> 07:21:48,920 RECORDS WILL ALL GO TO THE TUMOR 9790 07:21:48,920 --> 07:21:50,560 BOARD. THEY GET ON A ZOOM CALL. 9791 07:21:50,560 --> 07:21:53,600 ANY PROVIDER IN THE COUNTRY. 9792 07:21:53,600 --> 07:21:55,560 ACTUALLY, IN THE WORLD CAN 9793 07:21:55,560 --> 07:21:57,120 LISTEN IN TO WHAT 9794 07:21:57,120 --> 07:21:57,800 RECOMMENDATIONS ARE BEING GIVEN 9795 07:21:57,800 --> 07:22:00,880 AND WHY SOME TRIALS THAT THE 9796 07:22:00,880 --> 07:22:02,520 PATIENT WOULD BE INELIGIBLE FOR 9797 07:22:02,520 --> 07:22:04,200 AND WHY THEY WOULD BE ELIGIBLE 9798 07:22:04,200 --> 07:22:06,320 FOR AND TREATMENTS THAT ARE NOT 9799 07:22:06,320 --> 07:22:08,800 MAYBE THE BEST PRACTICES EVEN AS 9800 07:22:08,800 --> 07:22:11,000 A STANDARD OF CARE HASN'T 9801 07:22:11,000 --> 07:22:13,240 CHANGED IN 60 YEARS AND WE ARE 9802 07:22:13,240 --> 07:22:17,440 SEEING REAL WINS AND SEEING 9803 07:22:17,440 --> 07:22:20,000 PROACTIVE STEROID USE GO DOWN. 9804 07:22:20,000 --> 07:22:22,760 WE ARE SEEING ADJUNCTIVE 9805 07:22:22,760 --> 07:22:25,120 THERAPIES GO UP AND SEEING GAINS 9806 07:22:25,120 --> 07:22:29,400 IN OUTSIDE SURVIVAL AND EVEN 9807 07:22:29,400 --> 07:22:30,280 PROGRESSION-FREE SURVIVAL JUST 9808 07:22:30,280 --> 07:22:32,040 BECAUSE OF THE CHANGES IN HOW 9809 07:22:32,040 --> 07:22:33,280 THEY ARE TREATING THE 9810 07:22:33,280 --> 07:22:35,360 SIDE-EFFECTS IS IMPACTING THE 9811 07:22:35,360 --> 07:22:37,320 QUALITY OF LIFE AND FOR SOME 9812 07:22:37,320 --> 07:22:39,280 REASON THE LENGTH OF LIFE. 9813 07:22:39,280 --> 07:22:42,800 WE ARE EXCITED ABOUT THAT. 9814 07:22:42,800 --> 07:22:47,880 WE ALSO STAYED TOGETHER THEN, 68 9815 07:22:47,880 --> 07:22:49,720 FOUNDATIONS, AND STARTED 9816 07:22:49,720 --> 07:22:51,320 FUNTDING RESEARCH. IN FIRST 5 9817 07:22:51,320 --> 07:22:54,280 MONTHS FUNDED $1.1 MILLION IN 9818 07:22:54,280 --> 07:22:57,880 RESEARCH FOR DIPG/DMG. WE HAVE 9819 07:22:57,880 --> 07:22:59,440 ANOTHER ROUND OPEN NOW THAT WILL 9820 07:22:59,440 --> 07:23:02,720 FUND IN APRIL. SO, INSTEAD OF 9821 07:23:02,720 --> 07:23:04,080 WRITING GRANTS TO A WHOLE BUNCH 9822 07:23:04,080 --> 07:23:06,640 OF LITTLE FOUNDATIONS, YOU CAN 9823 07:23:06,640 --> 07:23:08,760 WRITE IT AT ONE PLACE. IT IS 9824 07:23:08,760 --> 07:23:15,000 REVIEWED BY A WONDERFUL MEDICAL 9825 07:23:15,000 --> 07:23:17,320 ADVISORY COUNCIL LED BY MICHELLE 9826 07:23:17,320 --> 07:23:20,760 MANJAY AND THOSE ACROSS THE 9827 07:23:20,760 --> 07:23:21,880 COUNTRY KNOWING ADVANCED 9828 07:23:21,880 --> 07:23:27,320 THERAPIES WELL THAT IS THE 9829 07:23:27,320 --> 07:23:29,200 DIPG/DMG RESEARCH FUNDING 9830 07:23:29,200 --> 07:23:31,000 ALLIANCE AND YOU CAN LOOK AT ANY 9831 07:23:31,000 --> 07:23:32,400 TIME. WE KNEW IT WAS IMPORTANT 9832 07:23:32,400 --> 07:23:34,320 TO CONTINUE CONVERSATIONS LIKE 9833 07:23:34,320 --> 07:23:36,640 THIS WITH RESEARCHERS, 9834 07:23:36,640 --> 07:23:37,640 CLINICIANS AND FAMILIES IN THE 9835 07:23:37,640 --> 07:23:41,400 FIGHT AND ADVOCATES AS WELL AS 9836 07:23:41,400 --> 07:23:43,160 POLICYMAKERS SO WE BUILD ON CURE 9837 07:23:43,160 --> 07:23:46,840 FAST THAT IS IN SEPTEMBER IN 9838 07:23:46,840 --> 07:23:47,680 WASHINGTON, DC EVERY YEAR. 9839 07:23:47,680 --> 07:23:49,400 WE ASK THOSE THAT ARE LEADING 9840 07:23:49,400 --> 07:23:52,960 NEW IDEAS WHETHER IT BE IN 9841 07:23:52,960 --> 07:23:54,320 PALLIATIVE CARE OR ALTERNATIVE 9842 07:23:54,320 --> 07:23:56,440 THERAPY OR TRIALS OR BASIC 9843 07:23:56,440 --> 07:23:58,200 RESEARCH TO COME TOGETHER FOR 9844 07:23:58,200 --> 07:23:59,840 WHAT IS NOW CALLED THE 9845 07:23:59,840 --> 07:24:05,080 BRAINSTORM SUMMIT. IT IS WIDER 9846 07:24:05,080 --> 07:24:06,920 THAN DIPG/DMG. IT IS ALL 9847 07:24:06,920 --> 07:24:08,720 PEDIATRIC BRAIN TUMORS. IF ANY 9848 07:24:08,720 --> 07:24:10,360 OF YOU ARE INTERESTED IN 9849 07:24:10,360 --> 07:24:11,360 PRESENTING NEXT YEAR, PLEASE 9850 07:24:11,360 --> 07:24:12,920 REACH OUT. WE WILL MAKE SURE 9851 07:24:12,920 --> 07:24:15,080 AND LOOK TO SEE WHETHER WE CAN 9852 07:24:15,080 --> 07:24:17,840 FIT YOU IN. LAST YEAR, WE HAD 9853 07:24:17,840 --> 07:24:20,360 500 PEOPLE PARTICIPATE. 9854 07:24:20,360 --> 07:24:22,120 SO, WHAT CAME OUT OF IT THAT WAS 9855 07:24:22,120 --> 07:24:24,280 REALLY INTERESTING. LIKE A 9856 07:24:24,280 --> 07:24:25,240 HOSPITAL ON THE EAST COAST 9857 07:24:25,240 --> 07:24:26,720 CALLING AND SAYING, DO YOU THINK 9858 07:24:26,720 --> 07:24:28,480 THE REASON THAT PEOPLE ARE NOT 9859 07:24:28,480 --> 07:24:30,480 ENTERING OUR TRIAL IS IF IT 9860 07:24:30,480 --> 07:24:31,840 DOESN'T WORK THEY CAN'T DO 9861 07:24:31,840 --> 07:24:33,520 ANYTHING ELSE UNTIL PROGRESSION? 9862 07:24:33,520 --> 07:24:35,440 YEAH. THAT IS PROBABLY A BIG 9863 07:24:35,440 --> 07:24:36,800 PART OF IT. 9864 07:24:36,800 --> 07:24:40,680 AS EXPLAINED BY A 13 YEAR OLD AT 9865 07:24:40,680 --> 07:24:42,000 THE TOUGH TOGETHER BREAKFAST. 9866 07:24:42,000 --> 07:24:45,680 SO, NOW THAT TRIAL IS AMENDED. 9867 07:24:45,680 --> 07:24:49,120 IF IT DOESN'T WORK, THEN THEY GO 9868 07:24:49,120 --> 07:24:52,480 STRAIGHT TO ONG201 COMPASSIONATE 9869 07:24:52,480 --> 07:24:53,600 USE BEFORE PROGRESSION. THERE 9870 07:24:53,600 --> 07:24:55,200 IS JUST THINGS LIKE THAT, THAT 9871 07:24:55,200 --> 07:24:56,640 WE CAN HELP WITH. 9872 07:24:56,640 --> 07:24:58,960 AND WE CAN NEVER TAKE YOUR 9873 07:24:58,960 --> 07:25:01,200 PLACE. TO THE EXTENT THAT WE 9874 07:25:01,200 --> 07:25:03,640 CAN MAKE YOUR WORK FASTER, 9875 07:25:03,640 --> 07:25:07,840 EASIER, MORE WELFUNDED, PLEASE 9876 07:25:07,840 --> 07:25:10,480 LEAN ON US IN WHATEVER TYPE OF 9877 07:25:10,480 --> 07:25:12,320 PEDIATRIC CANCER YOU ARE WORKING 9878 07:25:12,320 --> 07:25:12,640 WITH. 9879 07:25:12,640 --> 07:25:14,280 WE SOMETIMES STUMBLE UPON THINGS 9880 07:25:14,280 --> 07:25:16,040 THAT ARE INTERESTING TO US. 9881 07:25:16,040 --> 07:25:18,200 FOR YEARS, THOSE PARENTS THOUGHT 9882 07:25:18,200 --> 07:25:21,960 THAT THEY WERE CONSENTING TO 9883 07:25:21,960 --> 07:25:25,360 SHARING THEIR DATA JUST ASSUMED 9884 07:25:25,360 --> 07:25:27,200 WHEN ASSIGNING ALL CONSENT WILL 9885 07:25:27,200 --> 07:25:29,400 YOU SHARE YOUR DATA WITH 9886 07:25:29,400 --> 07:25:31,000 CHILDREN'S BRAIN TUMOR NETWORK 9887 07:25:31,000 --> 07:25:32,240 AND OTHERS THAT, THAT WAS 9888 07:25:32,240 --> 07:25:35,920 HAPPENING AND WE LEARNED THAT IN 9889 07:25:35,920 --> 07:25:38,440 2020 THAT JACE SAID HOW MANY 9890 07:25:38,440 --> 07:25:40,880 TUMORS THAT ARE FULLY SEQUENCED 9891 07:25:40,880 --> 07:25:45,160 DO YOU USE AT CBTN AND FOR DIPG? 9892 07:25:45,160 --> 07:25:48,480 THE ANSWER WAS WE HAVE ABOUT 9893 07:25:48,480 --> 07:25:48,720 480. 9894 07:25:48,720 --> 07:25:50,880 WE HAVE SEQUENCED I WANT TO SAY 9895 07:25:50,880 --> 07:25:55,600 IT WAS 69 OR 70 AT THE TIME. 9896 07:25:55,600 --> 07:25:57,800 WHY HAVEN'T YOU SEQUENCED THE 9897 07:25:57,800 --> 07:25:58,040 REST? 9898 07:25:58,040 --> 07:26:00,800 IT IS EXPENSIVE AND ABOUT $1500 9899 07:26:00,800 --> 07:26:03,160 A PERSON. THEY SAID, SO, WHO 9900 07:26:03,160 --> 07:26:04,360 MAKES THE PHONE CALLS? 9901 07:26:04,360 --> 07:26:06,000 WHAT PHONE CALLS? 9902 07:26:06,000 --> 07:26:08,160 WHO CALLS THE PARENT AND SAYS 9903 07:26:08,160 --> 07:26:10,040 THANK YOU FOR YOUR CHILD'S 9904 07:26:10,040 --> 07:26:12,440 BRAIN, BUT YOU FORGOT THE 9905 07:26:12,440 --> 07:26:15,080 PROCESSING FEE. IT IS IN THE 9906 07:26:15,080 --> 07:26:16,480 FREEZER. THAT IS KIND OF GROSS. 9907 07:26:16,480 --> 07:26:17,880 DON'T YOU THINK? 9908 07:26:17,880 --> 07:26:20,040 HE SAID, YEAH. DON'T WORRY. I 9909 07:26:20,040 --> 07:26:22,000 WILL GO GET IT RAISED. HOW MUCH 9910 07:26:22,000 --> 07:26:24,200 DO WE NEED? 9911 07:26:24,200 --> 07:26:24,920 (1) 500-0000. 9912 07:26:24,920 --> 07:26:28,440 SO, WITH COUNT ME IN AND BROAD 9913 07:26:28,440 --> 07:26:29,040 INSTITUTE AND [INDISCERNIBLE] 9914 07:26:29,040 --> 07:26:32,000 THOSE TUMORS WERE SEQUENCED THIS 9915 07:26:32,000 --> 07:26:34,640 LAST FALL AND CBTN CAME HERE TO 9916 07:26:34,640 --> 07:26:37,320 THE NIH WRITING A GRANT TO 9917 07:26:37,320 --> 07:26:40,320 SEQUENCE 6500 MORE SAMPLES OF 9918 07:26:40,320 --> 07:26:42,440 ALL TYPES OF PEDIATRIC BRAIN 9919 07:26:42,440 --> 07:26:43,160 TUMORS. 9920 07:26:43,160 --> 07:26:46,040 SO, AS THAT COMES IN AND BECOMES 9921 07:26:46,040 --> 07:26:48,000 HARMONIZED AND IS ABLE TO BE 9922 07:26:48,000 --> 07:26:50,440 ANALYZED, IT SEEMED TO US THAT 9923 07:26:50,440 --> 07:26:51,600 IMAGING AND CLINICAL RECORDS 9924 07:26:51,600 --> 07:26:53,280 SHOULD PROBABLY BE THERE TOO; 9925 07:26:53,280 --> 07:26:53,680 RIGHT? 9926 07:26:53,680 --> 07:26:56,840 THEY ARE NOT. NOT IN WIDE 9927 07:26:56,840 --> 07:26:58,560 SCALE. 9928 07:26:58,560 --> 07:27:00,280 SO, WE BROUGHT TOGETHER THROUGH 9929 07:27:00,280 --> 07:27:03,320 FUNDS AT CANCER MOON SHOT AMAZON 9930 07:27:03,320 --> 07:27:05,760 AND WEB SERVICES WITH 9931 07:27:05,760 --> 07:27:06,720 INFRASTRUCTURE UNDER WHICH MANY 9932 07:27:06,720 --> 07:27:09,160 OF YOU WORK AND CHILDREN'S BRAIN 9933 07:27:09,160 --> 07:27:11,280 TUMOR NETWORK AND FOUR OTHER 9934 07:27:11,280 --> 07:27:11,720 PARTNERS. 9935 07:27:11,720 --> 07:27:14,640 TOGETHER, THEY ARE WORKING ON AN 9936 07:27:14,640 --> 07:27:15,800 OBSERVATIONAL TRIAL THAT IN A 9937 07:27:15,800 --> 07:27:17,120 SHORT AMOUNT OF TIME WILL HAVE 9938 07:27:17,120 --> 07:27:23,440 THE CLINICAL RECORDS OF OVER 9939 07:27:23,440 --> 07:27:26,680 500DIPG/DMG PATIENTS AND 400 OF 9940 07:27:26,680 --> 07:27:29,560 WHICH ARE DECREASED AND 100 IN 9941 07:27:29,560 --> 07:27:31,520 THE FIGHT AND HOW IS THAT A 9942 07:27:31,520 --> 07:27:32,840 SHORT PERIOD OF TIME? 9943 07:27:32,840 --> 07:27:34,600 THEY ARE ON MY PHONE AND THEY 9944 07:27:34,600 --> 07:27:37,160 ARE ON MY FRIENDS LIST. ALL WE 9945 07:27:37,160 --> 07:27:40,040 HAVE TO DO IS ASK THE PARENT ARE 9946 07:27:40,040 --> 07:27:42,840 YOULE TO SHARE YOUR CHILD'S DATA 9947 07:27:42,840 --> 07:27:44,600 TO HELP THE NEXT CHILDREN? 9948 07:27:44,600 --> 07:27:49,240 AND THEY ARE GOING TO SAY YES. 9949 07:27:49,240 --> 07:27:53,160 I KNOW 361 PARENTS AND I 9950 07:27:53,160 --> 07:27:55,160 GUARANTEE 350 AT LEAST ARE 9951 07:27:55,160 --> 07:27:57,760 SAYING YES. 9952 07:27:57,760 --> 07:27:58,960 BECAUSE WHATEVER WE CAN DO TO 9953 07:27:58,960 --> 07:28:00,880 HELP IS WHAT WE WANT TO DO. WE 9954 07:28:00,880 --> 07:28:02,600 WANT TO BE ABLE TO PROVIDE THAT 9955 07:28:02,600 --> 07:28:04,760 IN A WAY THAT HELPS YOU THE MOST 9956 07:28:04,760 --> 07:28:07,040 THOUGH WHICH IS WHAT REQUIRES IT 9957 07:28:07,040 --> 07:28:10,920 THAT CONSTANT CONVERSATION. WE 9958 07:28:10,920 --> 07:28:17,440 WANT TO USE REPUTABLE GROWTH TO 9959 07:28:17,440 --> 07:28:20,080 FLOW INTO THE CCI AND WE CAN'T 9960 07:28:20,080 --> 07:28:22,320 WAIT. DIPG WON'T WAIT WE KNOW 9961 07:28:22,320 --> 07:28:28,440 IF WE TAKE SHOTS ON THE RIM YOU 9962 07:28:28,440 --> 07:28:30,480 NEED TO KNOW WHO HAS THE BALL 9963 07:28:30,480 --> 07:28:33,000 AND WHERE THE RIM IS AND WILL 9964 07:28:33,000 --> 07:28:34,200 TAKE WORK IN TRANSLATIONAL 9965 07:28:34,200 --> 07:28:37,760 SCIENCE. SO, THESE ARE THINGS 9966 07:28:37,760 --> 07:28:41,320 THAT WE FIND TO BE OUR HONOR AND 9967 07:28:41,320 --> 07:28:49,120 PRIVILEGE. WE CAN'T DO WHAT YOU 9968 07:28:49,120 --> 07:28:50,280 CAN DO. 9969 07:28:50,280 --> 07:28:52,720 YOU ARE GIVING OUR CHILD A 9970 07:28:52,720 --> 07:28:55,160 CHANCE. FOR THAT I AM 9971 07:28:55,160 --> 07:28:56,520 INTERNALLY GRATEFUL AND IS A 9972 07:28:56,520 --> 07:28:59,720 PRIVILEGE TO THANK YOU TODAY AND 9973 07:28:59,720 --> 07:29:03,520 TO SHARE WITH YOU WHAT MY VERY 9974 07:29:03,520 --> 07:29:06,520 GOOD FRIEND ADAM AT CBN SENT ME 9975 07:29:06,520 --> 07:29:08,880 IN A TEXT THAT IS A GREAT WAY TO 9976 07:29:08,880 --> 07:29:13,120 END THE DAY. I HAVE ZERO DOUBT 9977 07:29:13,120 --> 07:29:14,960 AND COMPLETE CONFIDENCE IN THE 9978 07:29:14,960 --> 07:29:16,560 ULTIMATE OUTCOME. OUR JOB IS TO 9979 07:29:16,560 --> 07:29:19,480 DO IT MUCH FASTER. 9980 07:29:19,480 --> 07:29:21,120 AS FAST AS POSSIBLE ON BEHALF OF 9981 07:29:21,120 --> 07:29:24,520 THE LEGACIES OF THOSE WHO 9982 07:29:24,520 --> 07:29:25,680 SACRIFICED AND THOSE THAT COME 9983 07:29:25,680 --> 07:29:27,120 AFTER THAT WILL NOT SUFFER. FOR 9984 07:29:27,120 --> 07:29:29,920 THAT MOMENT WHEN HUMANITY IS NO 9985 07:29:29,920 --> 07:29:32,520 LONGER AFRAID OF WHAT CANCER CAN 9986 07:29:32,520 --> 07:29:34,160 DO TO ITS CHILDREN BUT 9987 07:29:34,160 --> 07:29:36,800 CELEBRATES WHAT GROUPS OF 9988 07:29:36,800 --> 07:29:38,960 PASSIONATE PEOPLE DID WHEN THEY 9989 07:29:38,960 --> 07:29:41,520 CAME TOGETHER AND WHAT THEY 9990 07:29:41,520 --> 07:29:43,560 ACHIEVED TOGETHER ON BEHALF OF 9991 07:29:43,560 --> 07:29:47,120 CHANGING HISTORY. SO, ON BEHALF 9992 07:29:47,120 --> 07:29:52,640 OF NEUROCAR T-CELL PIONEER MARY 9993 07:29:52,640 --> 07:29:55,200 THE GIRL SCOUT YOU MET TURNING 7 9994 07:29:55,200 --> 07:29:57,680 IN APRIL AFTER 2 FULL YEARS OF 9995 07:29:57,680 --> 07:30:00,800 CAR T-CELL THERAPY, PLEASE BE 9996 07:30:00,800 --> 07:30:04,960 BRAVE. TRY TO BE NICE. THANK 9997 07:30:04,960 --> 07:30:12,520 YOU. 9998 07:30:12,520 --> 07:30:22,960 >> >> I THINK ALL OF THE 9999 07:30:23,360 --> 07:30:24,760 CHALLENGES WE HAVE TALKED ABOUT 10000 07:30:24,760 --> 07:30:27,800 OVER THE DAY WE SOLVED THEM FOR 10001 07:30:27,800 --> 07:30:30,760 DIPG. THANKS FOR YOUR POWERFUL 10002 07:30:30,760 --> 07:30:32,200 WORDS AND THANKS TO ALL OF THE 10003 07:30:32,200 --> 07:30:34,160 SPEAKERS AND CHAIRS AND TO 10004 07:30:34,160 --> 07:30:36,400 NIRALI FOR ARCHITECTING THIS 10005 07:30:36,400 --> 07:30:38,120 ENTIRE EVENT IN LIEU OF TIMING 10006 07:30:38,120 --> 07:30:40,080 WE WILL FOREGO CLOSING REMARKS 10007 07:30:40,080 --> 07:30:43,960 AND SAY SEE YOU AT INSPIRED 2.0. 10008 07:30:43,960 --> 07:30:45,800 >> THANK YOU, EVERYBODY. THANK 10009 07:30:45,800 --> 07:30:47,920 YOU TO THE AV TECH WHO STAYED 10010 07:30:47,920 --> 07:30:49,320 LATE. WE APPRECIATE YOU GUYS 10011 07:30:49,320 --> 07:30:59,560 MAKING THIS