>> GOOD AFTERNOON. I'M DR. BRIAN KAUFMAN FROM THE CLL SOCIETY, NON FOR PROFIT. THANK YOU ALL FOR COMING AND HELPING US LIVE UP TO THE MOTTO SMART PATIENTS GET SMART CARE BECAUSE I GUARANTEE AT THE END OF THE SESSION YOU'LL BE SMARTER FOR HAVING BEEN HERE. I'M GRATEFUL TO THE NATIONAL INSTITUTES OF HEALTH FOR OFFERING US THIS FACILITY AND MORE THAN THAT, OFFERING US THIS STELLAR FACULTY. SO YOU'LL HEAR TWO PARTS TO THIS. THERE'LL BE A LOT OF SCIENTIFIC STUFF AND WE'LL HAVE A Q&A AND A LOT OF TIME ON THAT TO GO OVER THAT AND THERE'S A SECOND PART TO THE MEET WHICH IS IS HOW TO CARE OF OURSELVES AND THE ADVOCATES AND THE SUPPORT SERVICE OF THE LYMPHOMA, LEUKEMIA SOCIETY. A COUPLE HOUSEKEEPING THINGS. IF YOUR CELL PHONE IS ON, IF YOU CAN PUT IT ON MUTE NOW, THAT WOULD BE HELPFUL. THE RESTROOMS ARE UP THERE TO THE LEFT AND A LITTLE FURTHER TO THE MEN'S THEN THE LADY'S. I'M GOING TO GO TO MY MAIN GO-TO PERSON WITH THE PROGRAM AND HAS DONE OUTSTANDING RESEARCH FOR OVER A DECADE, DR. ADRIAN REISNER. >> THANK YOU VERY MUCH. IT'S A GREAT PLEASURE TO SEE EVERYBODY HERE. IT'S AN ENORMOUS PRESSURE TO HAVE BRIAN KAUFMAN HERE SPEARHEADING THE WONDERFUL WORK FOR THE PATIENTS AS WELL AS BEING A WONDERFUL DISCUSSION PARTNER FOR ANYBODY THAT DOES RESEARCH IN CLL. SO GREAT PLEASURE TO WELCOME YOU HERE AND I WOULD LIKE TO TURN OVER THE PODIUM HERE TO WELCOME ADDRESS BY OUR CLINICAL DIRECTOR. AS MANY KNOW THIS IS REALLY THE PART OF THE CLINICAL CENTER OF NIH WHERE PATIENT-ORIENTED RESEARCH TAKE PLACE. SOME OF YOU, MANY OF YOU, HAVE BEEN HERE PARTICIPATING IN THIS RESEARCH. SO IT'S A GREAT PLEASURE TO HAVE DR. CHILDS TALK TO US FROM THE PERSPECTIVE OF A CLINICAL LEADER WITHIN THE INSTITUTION. >> GOOD AFTERNOON, EVERYONE. WELCOME TO THE NIH, THE NIH CLINICAL CENTER. I KNOW COMMANDER JULIE ALVAREZ GAVE YOU TOURS AND FOR MANY IT WAS THE FIRST TIME TO NIH SO I WANTED TO FORMALLY WELCOME YOU FOR BEING HERE AT THIS VERY IMPORTANT SYMPOSIUM. IT'S GREAT TO SEE SUCH A GOOD TURN OUT OF PATIENTS AND CAREGIVERS TODAY. ASIDE WELCOMING YOU, I WANTED TO TELL YOU ABOUT THE NIH AND THE NIH CLINICAL CENTER SO YOU WOULD GET AN APPRECIATION OF WHY WE BELIEVE THIS IS A VERY SPECIAL PLACE. A VERY UNIQUE PLACE IN THE WORLD'S MEDICAL RESEARCH INSTITUTIONAL ENVIRONMENTS. THE NIH BY HISTORY WAS ESTABLISHED BY AN ACT OF CONGRESS IN 1887. IT WAS INTENDED TO BE THE WORLD'S PREMIER MEDICAL RESEARCH INSTITUTION. I THINK THAT GOAL WAS ACCOMPLISHED. IT'S DIVIDED INTO INTRAMURAL AND EXTRAMURAL PROGRAMS. THERE ARE 27 INSTITUTES AN CENTER CONDUCT RESEARCH ON THIS CAMPUS. 20 OF THEM HAVE ACTIVE INTRAMURAL RESEARCH PROGRAMS THAT UTILIZE THE NIH CLINICAL CENTER. WE'D LIKE TO THINK OF THE CLINICAL CENTER AS BEING THE CROWN JEWEL OF ALL THE DIFFERENT BUILDINGS ON THE NIH CAMPUS. THERE'S REALLY NO OTHER PLACE LIKE THE NIH CLINICAL IN THE WORLD WHEN IT COMES TO THE WAY IT'S STRUCTURED AND IN TERMS OF THE KIND OF RESEARCH THAT'S CONDUCTED HERE. THE CLINICAL IS A HOSPITAL. IT'S GOT 220 BEDS. WE HAVE CLINICS, WE HAVE O.R.s AND OTHER ANCILLARY SUPPORT SERVICES YOU NEED TO TAKE CARE OF PATIENTS IN THE HOSPITAL. WHY DO WE HAVE THAT? BECAUSE WE'RE OFTEN TESTING NEW THERAPEUTICS IN PATIENTS. GIVING DRUGS AND IMMUNOTHERAPIES AND THERE'S ALWAYS THE POSSIBILITY THOSE MEDICATIONS CAN MAKE PATIENTS SICK. WE NEED TO BE IN AN ENVIRONMENT WHERE WE CAN SUPPORT THEM THROUGH ANY TOXIC PHASE OR DANGEROUS PHASE OF SUCH EXPERIMENTAL THERAPY. EVERY PATIENT THAT'S TREATED IN THIS HOSPITAL IS ON A RESEARCH PROTOCOL. WE DON'T GIVE CONVENTIONAL THERAPEUTICS PER SE, TO OUR PATIENTS COMING HERE. THEY MAY RECEIVE A CONVENTIONAL THERAPEUTIC COMBINED WITH SOME INVESTIGATIONAL DRUG OR SOME OTHER INVESTIGATIONAL COMPONENT TO THE STUDY. FOR INSTANCE, IMAGING. EVERYBODY HERE WE TREAT IS A RESEARCH SUBJECT AND OUR RESEARCH PARTNER. AND THAT'S REALLY UNIQUE AMONG ANY HOSPITAL OF THE WORLD. ALL CARE THAT'S DELIVERED HERE IS COMPLETELY FREE. WE SUPPORT OUR PATIENT'S TRAVEL AND HOUSING COSTS. WE'VE NEVER GIVEN A BILL TO A PATIENT. THEY TRIED TO CHANGE THAT FOUR YEARS AGO AND WE WERE ABLE TO PUSH BACK ENOUGH THAT FINALLY WE WERE ABLE TO PRESERVE THIS HOSPITAL AS A FREE INSTITUTION FOR OUR PATIENTS. THERE ARE CURRENTLY OVER 1600 ACTIVE CLINICAL RESEARCH PROTOCOLS BEING CONDUCTED IN THE NIH CLINICAL CENTER. OUR MAJOR EMPHASIS IS TO DO THINGS LIKE STUDY PATHOPHYSIOLOGY OF DIFFERENT DISEASES. WHAT'S THAT MEAN? THAT'S TO UNDERSTAND WHAT MAKES A DISEASE TICK. WHAT ARE THE CRITICAL ELEMENTS THAT MAKE A CANCER GROW OR SURVIVE BETTER THAN FORMAL CELL ORIGIN IT CAME FROM AND DEFINE THE VULNERABILITIES TO THAT CELL AND BE ABLE TO DEVELOP A TARGETED THERAPY GOING AFTER THOSE VULNERABILITIES. WE ALSO AIM TO TEST FIRST IN HUMAN NEW THERAPEUTICS FOR A VARIETY OF DIFFERENT DISEASES. AND WE TRIED TO CONDUCT STUDIES THAT CAN ONLY BE CONDUCTED IN A PLACE LIKE THE NIH. WHAT'S THAT MEAN? WELL, WE DEVELOPED LINES OF RESEARCH TO SUPPORT NEW THERAPEUTICS. THERE MAY BE EVIDENCE IN A PETRI DISH. THERE MAY BE EVIDENCE IN AN ANIMAL MODEL THAT SOMEBODY HAS ACTIVITY AGAINST A DISEASE LIKE CLL. IN ORDER TO GET GRANT SUPPORT YOU HAVE TO HAVE RIGOROUS LINES OF EVIDENCE AT MULTIPLE LEVELS. WHAT WE CAN DO HERE IS BECAUSE WE DON'T NEED GRANT SUPPORT BECAUSE WE'RE FUNDED ANNUALLY, YOUR TAX DOLLARS ARE WHAT SUPPORTS OUR RESEARCH, WE CAN DO STUDIES THAT MAYBE HAVE A SIGNAL THAT THERE'S SOMETHING NEW OR EXCITING BUT WHERE WE DON'T HAVE OVERWHELMING EVIDENCE WE WOULD PERHAPS NEED TO GET A GRANT TO FUND THAT STUDY. WE CAN BRING THE STUDIES VERY QUICKLY FROM THE BENCH TO THE BEDSIDE. OFTEN THESE STUDIES WILL FAIL BUT EVERY ONCE IN A WHILE WE'LL HIT ON SOMETHING VERY IMPORTANT. SOMETHING WE CALL PARADIGM SHIFTING. PROOF OF CONCEPT STUDIES THAT CAN LEAD TO AN ENTIRE NEW FIELD OF THERAPEUTICS FOR A DISEASE. OUR MOTTO IS FIT CAN BE -- IF IT CAN BE DONE SOMEWHERE ELSE, IT PROBABLY SHOULDN'T BE DONE HERE BEP WANT TO TAKE ADVANTAGE OF THE ENVIRONMENT TO CONDUCT STUDIES WHERE WE DON'T NEED GRANTS. SMALL STUDIES, PROOF OF PRINCIPLE STUDIES AND IF THEY WORK, PHASE III STUDIES, INDUSTRY MAY LICENSE OUR TECHNOLOGY OR WE MAY COLLABORATE BUT THE BIGGER STUDIES ARE CONDUCTED OUTSIDE THE NIH TO VERIFY WHAT THE OVERALL RESPONSE RATE IS OR TO BRING TO BEAR A NEW THERAPY TO A STANDARD THERAPY. WE HAVE STUDIES CALLED NATURAL HISTORY STUDIES. DR. REISNER HAS A NATURAL HISTORY STUDY FOR CLL AND THEY'RE VERY IMPORTANT. THE STUDIES ARE DESIGNED TO TRY TO GAIN INFORMATION ABOUT DIFFERENT SUBTYPES OF CLL. TO GIVE US INSIGHTS IN TERMS OF HOW WE SHOULD BEST TREAT PATIENTS INDIVIDUALLY BASED ON THINGS LIKE CHROMOSOMAL ABNORMALITIES OR OTHER MOLECULAR DISTINGUISHING FEATURES OF THEIR CLL WITH THE ULTIMATE GOAL OF DEVELOPING MEDICINE THAT'S TAILORED SPECIFICALLY TO INDIVIDUAL PATIENTS RATHER THAN ONE SIZE FITS ALL. WE KNOW ONE SIZE FITS ALL FOR THE MOST PART WILL NOT BE THE OPTIMAL THERAPY ALWAYS FOR SPECIFIC PATIENTS. THERE HAVE BEEN NUMEROUS ADVANCES IN MEDICINE THAT HAVE BECAUSE OF RESEARCH CONDUCTED AT THE CLINICAL CENTER. WE LIKE TO THINK OF THIS AS HALLOO HALLOOED -- HALLOWED GROUND AND THE FIRST MEDICINE TO TREATMENT CANCER WAS TESTED FOR AND THE USE OF BLOOD LIPID LEVELS AS BIOMARKERS TO DEFINE RISK FOR CARDIOVASCULAR DISEASE. THE FIRST STUDY BY THE FRAMINGHAM GROUP THAT SHOWED HIGH CHOLESTEROL WAS ASSOCIATED WITH CARDIOVASCULAR GEEZ -- CAME FROM NIH AND THE FIRST DEMONSTRATION YOU COULD USE THE HUMAN IMMUNE SYSTEM TO ATTACK, SHRINK AND CURE CANCERS WAS CONDUCTED HERE AT THE NIH CLINICAL CENTER. THE FIRST EVER GENE THERAPY WAS CON ZU CONDUCTED HERE INCLUDING NEW PROMISING GENE THERAPIES. IF YOU WATCHED 60 MINUTES THEY HAD A SEGMENT ON NIH AND GENE THERAPY THAT IS BEING CONDUCTED BY DR. TISDALE'S GROWL FOR PATIENTS WITH -- GROUP WITH PATIENT FOR SICKLE CELL ANEMIA THAT SHOWS PROMISE AND MAY BE ABLE TO CURE PATIENT. THOSE ARE THE EXCITING STUDIES WE HAVE HERE. THE FIRST EBOLA VACCINES WERE DEVELOPED HERE. COMING FROM DR. REISNER'S GROUP, SOME VERY IMPORTANT STUDIES IN CLL INCLUDING SOME BASIC STUDIES AT THE BENCH LEVEL THAT DEFINE THE IMPORTANCE IN BTK FOR CLL CELL'S ABILITY TO PROLIFERATE AND SURVIVE AND BEHAVE BADLY WITH THE HYPOTHESIS, THIS PARTICULAR NATURE OF THE CELL INTERRUPTING THERAPEUTICCALLY -- THERAPEUTICALLY MAY BE AN EFFECTIVE TREATMENT AND MANY HAVE RECENTLY GAINED FDA APPROVAL THAT HAVE SHOWN GREAT ACTIVITY. PARADIGM SHIFTING RESEARCH CONDUCTING BY DR. REISNER'S GROUPS AND OTHERS SHOWING EVEN IN THE WORSE FORM OF CLL WITH THE KIND OF PATIENTS I AS A TRANSPLANTER WAS ALWAYS REFERRED. THESE WERE PATIENTS WITH SHORT SURVIVAL. THESE DRUGS ARE BLOCKBUSTERS FOR THOSE PATIENTS AND ARE RESULTING IN LONG-TERM, DISEASE-FREE SURVIVAL. EXCITING WORE BY HIM AND HIS GROUP. THE LIST GOES ON AND ON FOR THE ADVANCES THAT HAVE BEEN MADE HERE AND I'M HOPEFUL THAT FIVE AND 10 YEARS FROM NOW I'LL BE ABLE TO COME UP TO THE PODIUM AND SPEAK TO A DIFFERENT GROUP AND TELL THEM THE DEFINITIVE CURES FOR CLL WERE DEVELOPED AT THE NIH. I'M EXCITED THAT DR. KAUFMAN AND DR. REISNER'S GROUP ARE LEADING THIS CONFERENCE. DR. REISNER AND HIS TEAM HAVE BEEN THE BUSINESS YEAST RESEARCH TEAMS WE HAVE IN THE NHLBI AND HAVE AN ACTIVE CLINIC AND HAVE INCREDIBLE SUBJECT MATTER EXPERT IN CLL AND HAVE BEEN DEEPLY IMPACTFUL FOR OUR PATIENTS WITH CLL. THAT'S IT. I'LL CLOSE AND THANK YOU ALL FOR COMING TO THIS SYMPOSIUM. WE'RE HOPEFUL YOU WILL GAIN INSIGHT YOUR DISEASE OR ABOUT YOUR LOVED ONE'S DISEASE THAT YOU'LL BE ABLE TO TAKE HOME THAT WILL BE OF DIRECT BENEFIT TO YOU HOPEFULLY. THANK YOU FOR COMING AND I HOPE HAVE YOU A GREAT MEETING. >> THANK YOU VERY MUCH FOR THE INSPIRING OPENING OF THIS AFTERNOON'S SESSION. VERY QUICKLY AS HOUSEKEEPING. WE HAVE A FEW PRESENTATIONS NOW ON DIFFERENT TOPICS. AS YOU SEE, THERE WILL BE A REFRESHMENT IN BETWEEN. THERE'S A QUESTION AND ANSWER SESSION AFTER THE FIRST BLOCK AND AFTER THE SECOND BLOCK. WHEN HAVE A QUESTION AFTER EACH TALK, IF YOU HAVE A PRESSING QUESTION FEEL FREE TO USE ONE OF THE MICROPHONES IN THE AISLE. IF YOU DON'T WANT TO SPEAK, I THINK THERE ARE CARDS AVAILABLE SO YOU CAN WRITE DOWN A QUESTION AND WE CAN ADDRESS THAT DURING THIS QUESTION AND ANSWER BLOCK AT THE END OF THE FIRST SESSION AND AT THE END OF THE SECOND SESSION. SO FEEL FREE TO ASK ANYTHING EITHER AT THE MICROPHONE OR WITH THE CARD. PLEASE KEEP IN MIND WE'RE ACTUALLY RECORDING AND LIVE STREAMING THIS. WE HAVE PEOPLE PARTICIPATING THROUGH ELECTRONIC LOGIN INTO THIS MEETING SO LET'S NOT DISCUSS PERSONAL THINGS AND TRY TO ANSWER AS CLL EXPERTS AND NOT NECESSARILY AS YOUR PRIVATE PHYSICIAN. I THINK THOSE CONVERSATIONS WE WOULD WANT TO HAVE IN OUR CLINIC ROOMS. SO LET'S KEEP THIS AS AN INFORMATIONAL SESSION IN GENERAL. THANK YOU ALL FOR COMING AND IT'S MY PLEASURE TO TURN OVER THE MICROPHONE TO DR. CLEESON. >> HI, EVERYONE. IT'S GREAT TO SEE FAMILIAR FACES AND ALSO A LOT NEW FACES I DON'T RECOGNIZE FROM CLINIC. WELCOME, EVERYONE. THE GOAL OF MY TALK IS TO PROVIDE AN OVERVIEW OF WHAT CLL IS FOR THOSE WHO MAY BE NEWLY DIAGNOSED TRYING TO UNDERSTAND WHAT THEIR DISEASE MEANS AND ALSO REVIEW SOME OF THE NEW DATA ABOUT THAT HAS CHANGED OUR THOUGHTS WITH THE CURRENT STANDARD OF TREATMENTS FOR CLL. IT'S ONE OF THE MOST COMMON LEUKEMIA. THE AVERAGE AGE OF DIAGNOSIS IS ABOUT 70 SO IT'S MOSTLY AN ELDERLY POPULATION THOUGH WE SEE SOME PATIENTS DIAGNOSED IN THEIR 30s. IT AFFECTS A CERTAIN TYPE OF WHITE BLOOD CELL CALLED B LYMPHOCYTE AND IT'S THOUGHT SPREAD TO THE LYMPH NODES AND SPLEEN AND LIVER. THE DIAGNOSIS OF CLL NOWADAYS IS USUALLY AN INCIDENTAL FINDING PATIENTS OBTAIN A ROUTINE BLOOD COUNT AT THEIR DOCTOR'S OFFICE. USUALLY WHAT WE SEE IS THAT THE PATIENTS ARE FOUND TO HAVE AN INCREASED WHITE COUNT AND SUBSEQUENT WORK-UP REVEALS THE CLL CELLS. ALTERNATIVELY, SOME PATIENTS MAY NOTICE LUMPS OR BUMPS THAT ARE IN FACT LARGE LYMPH NODES ON EXAMINE COMMONLY AFFECTING THE NECK AREA OR UNDER ARMS. THE DIAGNOSIS OF CLL IS MADE BY A UNIQUE PATTERN OF EXPRESSION OF CERTAIN PROTEINS ON THE SURFACE OF THE CLL CELLS. SO WHEN PATIENT DIAGNOSED, THEIR DOCTORS MAY FORM A TEST KNOWN AS FLOW CYTOMETRY WHICH IS A TEST USING A LASER THAT TRIES TO IDENTIFY THE TYPES OF PROTEINS EXPRESSED ON THE SURFACE OF THE CELL. AND FOR CLL, THE USUAL MARKERS THAT COME UP AND THIS MAY COME UP IN YOUR DISCUSSION WITH YOUR PRIMARY ONCOLOGIST AS WELL IS THAT CLL CELLS ARE CD5 POSITIVE AND CD20 POSITIVE AND WE ALSO EXPRESS A B CELL RECEPTOR WHICH IS THE FOCUS OR THE TARGET OF SOME OF THESE NEWER THERAPIES THAT WE WILL TALK ABOUT. CLL CAN OCCUR ON THE SPECTRUM. SO CLL IS A LEUKEMIA DISEASE. IN ORDER FOR THE DIAGNOSIS TO BE MADE THERE HAS TO BE OVER 5,000 LEUKEMIA CELLS PER MICROLITER OF BLOOD. ON THE OTHER HAND, THE SAME KIND OF CELLS CAN BE FOUND IN THE LYMPH NODE AND WHEN THEY PRESENT WITHOUT A THE BONE COMPONENT WE CALL THIS SLL. WHEN WE INSPECT THE PATTERN OF PROTEIN EXPRESSION THEY'RE ESSENTIALLY THE SAME. DEF LIEU AND WHEN PATIENTS HAVE MBL, THEY DON'T REALLY HAVE A CANCER AT ALL BUT THEY HAVE CELLS THAT LOOK LIKE CLL THAT'S DETECTABLE IN THE BLOOD THAT DON'T QUITE MEET CRITERIA FOR CLL IN TERMS OF THE 5,000 CUT OFF AND THEY DON'T HAVE ANY ENLARGED LYMPH NODE OR OTHER COMPLICATES RELATED TO CLL OR SLL. THERE'S ALSO A SPECTRUM IN AND OF ITSELF WITHIN MBL I DON'T WANT TO GO INTO TOO MUCH DETAIL AND MBL LESS THAN 5,000 COULD BE AS LOW AS 20 CELLS OR 10,000 CELLS. THAT'S ALSO SOMETHING WE KEEP IN MIND WHEN PATIENTS PRESENT WITH MBL. HOW IS CLL STAGED? IN THE U.S. WE USUALLY USE THE STAGE RANGING 0 THROUGH 4. IN THE EARLIEST STAGE ONLY LEUKEMIC CELLS ARE DETECTED IN THE BLOOD THE PATIENT DOESN'T HAVE ENLARGED LYMPH NODE OR ENLARGED SPLEEN. WHEN THE PATIENT ADVANCES TO STAGE 1 OR 2, NOT ONLY ARE THERE DETECTABLE LEUKEMIC CELLS IN THE BLOOD BUT THE PATIENT ALSO HAS ENLARGED LYMPH NODES OR SPLEEN AND THE CLL CAN CONTINUE TO PROGRESS TO A MORE ADVANCED STAGE, 3 OR 4. WHAT THIS MEANS IS THE CLL HAS INFILTRATED ENOUGH OF THE BONE MARROW TO AFFECT THE PRODUCTION OF BLONORMAL BLOOD CELLS. THIS TRANSLATES TO EITHER LOW RED CELL COUNT OR LOW PLATELET COUNT. THERE ARE MANY MARKERS THAT HAVE BEEN DEVELOPEDED TO HELP US PREDICT HOW AGGRESSIVE A CLL CAN BE. IN SOME PATIENTS IT MAY PROGRESS SO SLOWLY THEY MAY NEVER REQUIRE TREATMENT AND IN OTHERS IT CAN PROGRESS QUICKLY LEADING TO SYMPTOMS AND THE NEED FOR THERAPY. I JUST LISTED SOME OF THE MOST COMMON MARKERS WE USUALLY USE IN CLINIC TO TRY TO HELP US PREDICT HOW AGGRESSIVE A CLL COULD BE. IN GENERAL WE LIKE KNOW THE STAGE, WHICH I'VE REVEALED, AND WE LIKE TO SEE HOW QUICKLY THE LYMPHO CELL COUNT PROGRESSES AND SOME OF THESE GENETIC MARKERS IGHB, MUTATIONS, THEY'RE VERY IMPORTANT FOR US TO ASSESS THE RISK OF CLL OR PREDICTING HOW QUICKLY THE CLL WILL PROGRESS WITHOUT TREATMENT OR ALSO TO HELP US IDENTIFY THE BEST TREATMENTS FOR YOUR PARTICULAR SUBTYPE OF DISEASE. SO YOU MAY HAVE HEARD THAT ABOUT YOUR IGHB MUTATIONAL STATUS WE CONSIDER THE UNMUE MATED IGHV AS LESS CLL AND WE LOOK TO PERFORM A TEST THAT LOOKS AT CHROMOSOMAL OR GENE STRUCTURAL ABNORMALITIES INSIDE THE CELLS AND IN PATIENTS THE STRUCTURAL ABNORMALITIES ARE EITHER THE LOSS OF THE 17P OR Q CHROMOSOMES. SOME OF THESE MUTATIONS I'VE LISTED HAVE BECOME MORE AND MORE IMPORTANT IN OUR INFORMATION OF CLL AND TP53 IS ONE WE ALWAYS HEAR ABOUT IN THINKING HOW AGGRESSIVE IT WILL BE IN TERMS OF TREATMENT DECISIONS. AND MORE RECENTLY, SF3B1 HAVE BECOME INCORPORATED NOT SO MUCH IN TERMS OF GUIDELINES BECAUSE I DON'T THINK IT'S QUITE THERE YET BUT IN TERMS OF INVESTIGATING NEW TREATMENT FOR THESE PATIENTS CARRYING THESE MUTATIONS. THEN WE HAVE ALSO SOME ADDITIONAL FLOW CYTOMETRY. THAT'S THE LASER I DESCRIBED THAT'S COMMONLY USED TO DIAGNOSIS -- DIAGNOSE THAT CAN LOOK AT BIOMARKERS LOOKING AT OTHER RISK OF THE DISEASE AND OTHER MARKERS CD49C AND CD38 THAT MAY BE ASSOCIATED WITH MORE LOOK AT MARKERS IN THE BLOOD. HDH AND BETA 2 ARE TWO MARKERS WE COMMONLY USE TO INFORM US IN TERMS OF HOW AGGRESSIVE YOUR DISEASE IS. SO WITH SO MANY PROGNOSTIC MARKERS, IT CAN BECOME DIFFICULT FOR A PATIENT AND FOR A DOCTOR AS WELL TO FIGURE OUT EXACTLY WHERE THIS PLACES YOU ESPECIALLY IF THERE COULD BE CONFLICTING PROGNOSTIC MARKERS AND BEING A HIGH RISK IN ONE CATEGORY AND LOW RISK IN ANOTHER TYPE OF MARKER AND TO ADDRESS THE QUESTION, THERE'S BEEN AN EFFORT TO TRY TO IDENTIFY THE MOST IMPORTANT RISK FACTORS ASSOCIATED WITH AGGRESSIVE DISEASE. SO ONE ATTEMPT TO DO THIS WAS FROM THE INTERNATIONAL CLL NATIONAL PROGNOSTIC INDEX WORKING GROUP. HERE I LISTED IN THE BLUE TABLE THE FIVE PROGNOSTIC MARKERS THEY HAVE USED TO TRY TO COME UP WITH A SCORE TO PREDICT SURVIVAL IN PATIENTS WHO ARE TREATMENT NAIVE AND RECEIVE CHEMOTHERAPY AS A FRONTLINE AGENT. I STRESS THAT BECAUSE IT'S NOT BEEN USED SO MUCH IN PATIENTS RECEIVING TARGETING THERAPIES WHICH ARE BECOMING MORE COMMONPLACE FOR CLL PATIENTS. FOR THOSE WHO DON'T REQUIRE TREATMENT RIGHT AWAY, MANY ENTER INTO WATCH AND WAIT OR SOME WOULD SAY WATCH AND WORRY WHERE MONITORED BY THEIR DOCTOR WITHOUT RECEIVING ANY TREATMENT. WITH THAT MEANS IS USUALLY LAB TEST TO LOOK AT THE COMPLETE BLOOD COUNT. LOOKING AT THE NUMBER OF CLL CELLS IN THE BLOOD AND RED BLOOD CELLS AND PLATELETS. PERFORMING A PHYSICAL EXAM TO MONITOR THE SIZE OF LYMPH NODES AND SPLEEN AND ELICIT SYMPTOMS SUCH AS FATIGUE, WEIGHT LOSS, SYMPTOMS THAT COULD BE ATTRIBUTED TO ACTIVE CLL. THE REASON FOR THIS IS THAT WE CHOOSE THIS APPROACH AND THE JUSTIFICATION OF THIS CAME FROM A VERY EARLY PAPER IN 1999 FROM A CLL TRIAL GROUP AND PATIENT WHO'S EITHER DEFERRED CHEMOTHERAPY OR TREATED WITH CHEMOTHERAPY RIGHT AWAY AND WHAT THEY FOUND IS THERE WAS NO DIFFERENCE IN TERMS OF OVERALL SURVIVAL BETWEEN WAITING AND GETTING TREATED RIGHT AWAY. THAT'S BASICALLY INFORMED HOW WE TREAT CLL TO THIS DAY. WE KNOW UP TO 30% OF PATIENTS WILL NEVER AND THIS WATCH AND WAIT WILL HELP US AVOID POTENTIAL SIDE EFFECTS IN TREATMENT. IN THE AREA OF TARGETED TRETMENT THAT QUESTION IS BEING RE-ADDRESSED. SIT POSSIBLE ONE TREATMENT CAN BE BETTER THAN NO TREATMENT IN EARLY STAGE CLL. AND TO THE RIGHT, THIS IS THE TRIAL DESIGN FOR A TRIAL BEING PERFORMED IN GERMANY WHERE PATIENTS WITH EITHER INTERMEDIATE OR HIGH CLL ARE BEING RANDOMIZED TO EITHER THE MEDICATION OR THE PLACEBO AND IT'S IMPORTANT IN TERMS OF HEMP US UNDERSTAND THE DIFFERENCE. SO WHAT DETERMINES THIS? ONE IS IF PATIENTS DEVELOP PATIENTS RELATED TO CLL. AND THAT COULD BE WEIGHT LOSS, FATIGUE, FEVERS AND NIGHT SWEATS. ANY OF THESE CRITERIA COULD MEAN TREATMENT IS NEEDED. SO ONE DOESN'T NEED TO CHECK ALL THE BOXES IN ORDER FOR TREATMENT TO BEGIN. THE NEXT SECOND HALF OF MY TALK I WANTED TO REVIEW SOME OF THE CURRENT STANDARDS FOR CLL. WHAT WE KNOW SO FAR. A LOT OF IMPORTANT STUDIES HAVE BEEN DONE OR PUBLISHED IN THE PAST YEAR. IT'S A VERY EXCITING TIME FOR CLL. BEFORE THE LAST YEAR OR SO, THE STANDARD FRONTLINE THERAPY FOR CLL WAS FCR AND BR FOR MANY PATIENTS. ONE IMPORTANT STUDY THAT ATTEMPTED TO ADDRESS WHETHER FCR AND TWO CHEMOTHERAPY REGIMENTS WERE DIFFERENT IN TERMS OF THEIR CLINICAL OUTCOME WAS PERFORMED BY THE GERMAN CLL STUDY GROUP. EACH LINE REPRESENT THE GROUP THAT RECEIVED FCR OR BR AND 100% OF THE PATIENTS AT THE BEGINNING OF TREATMENT WERE ALIVE AND PROGRESSION FREE. AND THEN THE DISEASE RELAND -- RELAPSE ORDER THEY DECIDE OF OTHER CAUSES. WHAT I'M TRYING TO ILLUSTRATE IS THE CURVES DIVERGE. IT APPEARS FCR IS THE MORE EFFECTIVE THERAPY AND THE MEDIAN PROGRESS-FREE SURVIVAL IS 55.2 MONTHS COMPARED TO 44.7 MONTHS WITH BR SO MORE THAN A YEAR'S DIFFERENCE. BUT WHEN YOU LOOK AT THE SIDE EFFECTS YOU CAN SEE THE FCR IS ASSOCIATED WITH MORE SIDE EFFECTS. WHEN THE INVESTIGATORS PERFORMED A SUBGROUP ANALYSIS AND MAYBE IN THE ELDERLY GROUP, FCR MAY NOT BE THE BEST REGIMENT BECAUSE OF THE ASSOCIATED TOXICITIES. IN THE RECENT YEARS BECAUSE OF HOW MUCH IBRUTINIB WAS COMPARED TO OTHER COMMON THERAPY STANDARDS. THIS WAS A STUDY THAT RANDOMIZED PATIENTS CONSIDERED YOUNG WITH UNTREATED CLL TO FCR OR IBRUTINIB RITUXIMAB AND THE LINE IS THE CHEMOTHERAPY GROUP AND BOTH PROGRESSION-FREE AND OVERALL SURVIVAL APPEARED TO BE SUPERIOR IN PATIENTS RECEIVE IBRUTINIB-BASED THERAPY. IN THIS STUDY IN THE SUBGROUP ANALYSIS WHAT INVESTIGATORS FOUND WAS IN THE MUTATED IGHB GROUP THERE DID NOT SEEM TO BE A DIFFERENCE IN TERMS OF PROGRESSION-FREE SURVIVAL. EVEN BEFORE THAT, BACK IN 2016, THERE WAS A LONG-TERM FOLLOW-UP PAPER OF OVER 300 PATIENT WHO'S RECEIVED FCR FOR THEIR CLL. AND WHAT THIS LONG-TERM FOLLOW-UP DEMONSTRATED WAS THAT AFTER 12 YEARS OF FOLLOWING UP POST FCR, OVER HALF THE PATIENTS WITH MUTATED IGHC REMAINED PROGRESSION-FREE AND ALIVE. WHAT THIS MEANS IS THAT IN THOSE PATIENTS YOUNG, FIT, ABLE TO TOLERATE FCR WITH MUTATED IGHV IT'S THE -- STILL A REASONABLE CONSIDERATION. IN ADDITION, THE LONG-TERM SURVIVORS, THOSE WHO HADN'T PRO PROGRESSED AFTER THE 10-YEAR TIME POINT THEY DIDN'T HAVE DETECTABLE DISEASE SUGGESTING THEY MAY HAVE BEEN CURED WITH THE TREATMENT CYCLE OF SIX MONTHS OF THERAPY. DEF WHAT ABOUT THOSE IN THE OLDER COMMUNITY? ONE OF THE COOPERATIVE GROUPS RANDOMIZED PATIENT WHO'S WERE OLDER THAN 65 TO EITHER RECEIVING BR OR IBRUTINIB PLUSRY TUX MAN -- PLUS RITUXIMAB AND THE DARK LINES ARE THE BR GROUP. WHAT THE CURVE IS MEANT TO ILLUSTRATE IS THE IBRUTINIB PATIENTS DID BETTER. BASED ON RECENT DATA REPORTED, ONE CAN CONSIDER IBRUTINIB AS THE FRONTLINE TREATMENT FOR PATIENTS WITH THE EXCEPTION I ILLUSTRATED WITH MUTATED IGHV YOUNG PATIENTS NO OTHER ADVERSE GENETIC FACTORS. AND IBRUTINIB IS ALSO NOTED IN THE RELAPSE AND I DIDN'T WANT TO GO TOO MUCH INTO THAT WITH TIME AND A NEW CLASS IS RITUXIMAB AND THIS REGIMENT IS CONSIDERED ONE OF THE RECOMMENDED THERAP YES NOW FOR RELAPSE CLL. BY THE GROUP. SO THE DATA BEHIND THIS IS THE MORANO STUDY WHICH IS WHAT I'M SHOWING HERE IN WHICH OVER 350 PATIENT WITH RELAPSED OR REFRACTORY CLL WERE RECEIVED RITUXIMAB IN COMBINATION AND THE CURVE DISPARATE. THE GREEN ARE THE VENETOCLAX GROUPS AND IT WAS SUPERIOR COMPARED OTHER IN THE STUDY. I THINK INITIAL TREATMENT WITH IBRUTINIB IS RECOMMENDED FOR MOST PATIENTS EXEMPT YOUNG PATIENTS WITH MUTATED IGHV WHO COULD CONSIDER FCR WITH THE POSSIBILITY OF CURE. AND THE TWO MOST THERAPIES ARE IBRUTINIB AND RITUXIMAB AND VENETOCLX AND FOR PATIENTS WITH UNTREATED CLL ON WATCH AND WAIT OR THOSE RECEIVING TARGETED THERAPY FROM THEIR LOCAL ONCOLOGIST, WE HAVE A NATURAL HISTORY STUDY WHERE WE'RE TRYING TO UNDERSTAND THE BIOLOGY OF DISEASE BOTH WITHOUT TREATMENT AND ON THE TARGETED AGENTS. IF YOU ARE INTERESTED PLEASE REACH OUT TO OUR GROUP. WITH THAT, I'M GOING TO END AND I'LL BE HAPPY TO ANSWER ANY QUESTIONS. THANK YOU. I THINK I'LL MOVE ON THEN. >> MY TALK IS GOING TO BE CUT SHORT. THE ADMIRAL WENT OVER MOST IT AND FOR MOST WHO DON'T KNOW ME, I HAVE BEEN AT THE CLINICAL CENTER 20 YEARS BUT JUST FOR THE LAST THREE YEARS I'VE BEEN WITH DR. REISNER'S GROUP. I GAVE THIS TALK LAST YEAR AND I DID A LOT OF TOOTING OF THE CLINICAL CENTERS HORN WHICH ADMIRAL CHILD'S DID AND I THINK IT IS AN EXTRAORDINARY PLACE AND DESERVES MENTION AND THEN I'LL GET IN THE MEAT OF THE TALK AND WHAT RA CLINICAL TRIALS AND -- WHAT ARE CLINICAL TRIALS AND WHY YOU SHOULD PARTICIPATE. THE BUILDING IS INSPIRING AND A SUPER IMPRESSIVE FACILITY. THE BIGGEST BUILDING IN THE WORLD 3.3 MILLION SQUARE FEET AS MENTIONED IN THE GUINNESS BOOK OF WORLD RECORDS AND THE TENANT BUILDING IS THE HOT BED OF CLINICAL ACTIVITY AND HOUSES NOT ALL THE 27 INSTITUTES AND CENTERS, JUST A FEW OF THEM, BUT IT IS WHERE ALL THE CLINICAL ACTIVITY AND RESEARCH TAKE PLACE. I WANTED TO SAY SOME INSTITUTE US MAY HAVE HEARD OF, NATIONAL HEART INSTITUTE AND NATIONAL INSTITUTES OF MENTAL HEALTH, NIAID, WE FALL AS THE CLL GROUP UNDER THE LYMPHOID MAMMAL -- MAM IL NANCY GROUP -- MALIGNANCY GROUPS AND SOME FUN FACTS, WE HAD 9700 NEW PATIENTS IN 2017. MORE THAN 4500 INPATIENT ADMISSIONS AND 2,000 OUT-PATIENT VISITS EACH YEAR IN 2017 ALONE.- PATIENT ADMISSIONS AND 2,000 OUT-PATIENT VISITS EACH YEAR IN 2017 ALONE.PATIENT ADMISSIONS AND 2,000 OUT-PATIENT VISITS EACH YEAR IN 2017 ALONE. I THINK THIS IS REMARKABLE BECAUSE I'VE GIVEN TALK TO ROTARY CLUBS AND THERE'S NOT A HOSPITAL HERE. WE DO EVERYTHING EXCEPT OBSTETRICS AND ORTHOPEDICS BUT THERE'S A LOT GOING ON PEOPLE DON'T KNOW ABOUT. WE HAVE 1200 PHYSICIANS AND Ph.D.s AND OVER 600 NURSES AND A BUNCH OF PARM -- PHARMACISTS AND AN EXTRAORDINARY STAFF OF EXPERTISE WE BRING TO THE TABLE TO CONDUCTED THE IMPORTANT RESEARCH WE TO HERE. WE DO HERE. WITH THAT IN MIND, I WANT TO KEEP MOVING ON TO I THINK DR. CHILDS DID COVER THE DIFFERENT TYPE OF SERVICES. HEALTH SERVICES IS AN INTERESTING ONE. I'LL DIGRESS FOR A MOMENT. IT'S INTERESTING TO THINK OF HOW INSURANCE PLAYS OUT AND I WAS SPEAKING ABOUT HOW INSURANCE PLAYS A FACTOR IN TREATMENT DECISION WHICH IS INTERESTING TO CONSIDER. WE DO CONDUCT RESEARCH TO EVALUATE HEALTH INSURANCE AND HOW IT IMPACTS QUALIT OF LIFE AND THE DECISIONS WE MAKE. IT'S AN INTERESTING SIDE NOTE. WE CAN LOOK AT TRIALS THAT LOOK AT NEW DRUGS OR COMBINATIONS OF DRUGS. WE MAY BE TWEAKING FOR EXAMPLE, IF THERE'S A TRIAL CONDUCTING RESEARCH ABOUT IBRUTINIB, YOU MAY SAY IT'S APPROVED IN THE COMMUNITY BUT WE MAY BE LOOK AT IT FROM A DIFFERENT ANGLE OR COMBINATION OR PERHAPS THERE'S A NEW WAY OF DOING A NEW TYPE OF SURGERY. THERE'S A NEW DEVICE LOOKING FOR FDA APPROVAL. MAYBE A WAY TO JUST IMPROVE ON AN EXISTING TREATMENT. SAY YOU'RE DOING A TRANSPLANT AND YOU'D LIKE TO DECREASE THE INCIDENT OF GBHB TO TRY TO IMPROVE THE OUTCOMES AND TOLERABILITY OF THE TRANSPLANT. WE'RE ALWAYS LOOKING FOR NEW WAYS TO IMPROVE THE QUALITY OF LIFE FOR PEOPLE WHO SUFFER FROM ACUTE OR CHRONIC ILLNESSES. HOW'S DOES ALL RESEARCH START? IN THE LAB. I ALWAYS GET A THRILL WHEN YOU GO INTO DR. REISNER'S LAB AND YOU THINK OF WHAT GREAT NEW IDEA WILL THEY COME UP WITH NEXT IT STARTS IN THE LAB WITH AGE AN IDEA AND AFTER THEY DO TESTING WITH BENCH OR ANIMALS AND IT'S DEVELOPED INTO A PROTOCOL. YOU HEAR US USE THE WORD PROTOCOL A LOT. WHAT EXACTLY IS A PROTOCOL? IT'S BASICALLY THE ROAD MAP FOR WHAT WE DO. MANY TIMES PEOPLE WILL SAY, WELL, CAN I COME BACK IN NINE DAYS AND I SAY, NO, THE PROTOCOL SAYS IT HAS TO BE WITHIN A FIVE-DAY WINDOW. IT'S A PRETTY STRINGENT ROAD MAP BUT THE REASON IS IN ORDER NOR DATA TO BE MEANINGFUL WE NEED TO BE COMPARING APPLES TO APPLES. WE HAVE TO HAVE EVERYBODY DOING THE SAME THING AND FOLLOWING THE SAME RULES AND FORMULAS SO WE CAN COME TO GOOD CONCLUSIONS AND OUR DATA WILL BE GOOD. WHAT ARE SOME COMPONENTS OF THE PROTOCOL. YOU MIGHT SEE US TALKING ABOUT WHAT'S THE GOAL? WHAT ARE WE TRYING TO FIND OUT? WHAT'S THE QUESTION THAT WE'RE LOOKING TO ANSWER ALSO THE PROTOCOL WILL DICTATE WHO'S ELIGIBLE FOR THE TRIAL AND WHAT CRITERIA THEY NEED TO BE MEET TO BE ABLE TO PARTICIPATE IN THE RESEARCH. IT THE WILLING GIVE DETAILS ABOUT THE PROCEDURES AND LAB TESTS AND ANY KIND OF MONITORING WE'LL BE DOING THROUGHOUT THE STUDY. AND IT WILL TELL YOU HOW LONG THE TRIAL'S MEANT TO LAST AND ALSO WHAT INFORMATION WE'RE GOING GATHER. SPECIFICALLY, WHAT INFORMATION DO WE NEED TO GATHER TO MAKE THAT RESEARCH STATISTICALLY SIGNIFICANT. WE CAN SAY THAT WORKS BUT IF IT'S NOT STATISTICALLY SIGNIFICANT IT WON'T GO ON TO BECOME A PHASE III STUDY WHERE THEY TESTING IT IN THE COMMUNITY AGAINST THE STANDARD OF CARE THAT'S ACCEPT. ONE THING IN PROTOCOLS AND CLINICAL TRIALS, IF YOU'RE THINKING OF PARTICIPATING IN A RESEARCH STUDY YOU SHOULD BE AWARE AND QUESTION IF IT'S AN IRB PROTOCOL AND AT THE REVIEW BOARD. ALL THE PROTOCOLS AT THE NIH ARE COVERED BY AN IRB. IT BASICALLY SAY COMMITTEE RESPONSIBLE FOR OVERSEEING THE SAFETY AND GIVING GUIDELINES HOW TO PROTECT PATIENT SAFETY AND MAKE SURE THE RESEARCH IS BEING DONE PROPERLY. SO FIRST AND FOREMOST IT PROTECTS YOU. IF YOU'RE PARTICIPATING IN A CLINICAL TRIAL AND YOU WANT TO MAKE SURE YOU HAVE THE UMBRELLA OF THE IRB OVER YOU AND KEEPS US IN CHECK WHICH IS A GOOD THING AS WELL. SOME OF THE CLINICAL TRIALS AND I SEE FAMILIAR FACES AND I DON'T KNOW WHO'S ON THE WEBCAST BUT I'M SURE THERE'S PEOPLE WHO CAN USE REVIEW AND A LOT OF YOU COULD PROBABLY TEACH ME A THING OR TWO ABOUT REVIEW BUT IT'S INTERESTING AND THERE'S DIFFERENT PHASES. YOU'LL HEAR US TALK ABOUT THE PHASE MUCH A CLINICAL TRIAL. PHASE 1 LOOKS PRIMARILY AT TOXICITY AND WE'RE LOOKING NOR MAXIMUM TOLERATED DOSE AND WHAT THE SIDE EFFECTS ARE AND HOW MUCH DRUG IS THE APPROPRIATE DRUG AND WHAT ARE THE SIDE EFFECTS. GENERALLY THEY'RE SMALLER STUDIES AND WITH THE INFORMATION WE GATHER WE CAN PROGRESS TO PHASE 2. PHASE 2 IS A LITTLE BIT LARGER TRIAL 100 TO 300 PEOPLE. THAT'S CHECKING, DOES THIS WORK, WHAT'S THE RESEARCH QUESTION WE'RE LOOKING AT AND DOES IT WORK. WE'VE LOOKED AT THE MAXIMUM DOZE AND DETERMINED WHAT THE TOXICITIES ARE AND DOES IT WORK. GOING TO PHASE 3 STUDIES LESS COMMONLY DONE HERE, YOU'RE LOOKING AT A MUCH LARGER POPULATION. THEY'RE MORE LIKE 1,000 TO 3,000 PEOPLE. THAT'S CONFIRMING THE EFFECTIVENESS OF THE STUDY AND THOSE ARE REALLY WHAT SHIFTS THE PARADIGM IN TERMS OF THE TREATMENT DECISION. SO MAY COME UP WITH THE GREEN THAT SHOWS IT SHOWS PROMISE BUT IT'S THE PHASE III STUDY THAT ULTIMATELY GIVES IT THE TEETH TO CHANGE THE TREATMENT DECISION PROCESS. THE PHASE IV TRIALS, WE'RE NOT REALLY INVOLVED IN. THEY'RE MOPOST-MARKET. THEY'RE AFTER SOMETHING'S APPROVED AND THEN THE COMPANY GOES BACK AND RESEARCH IS DONE TO TRACK IN THE GENERAL POPULATION, IS THIS DRUG DOING WHAT WE SAID AND WHAT ARE THE TOXICITIES WE'VE SEEN AFTER APPROVAL AND IT'S ANOTHER CHECK IN THE SYSTEM TO FINISH THE. -- FINISH THE RESEARCH. WHAT DO THE TRIALS MEAN TO PATIENTS WITH CLL? LIKE MENTIONED, WE HAVE MADE EXTRAORDINARY LEAPS WITH DISCOVERY AT THE BTK. WE CHANGED THINGS DRAMATICALLY FROM 10 YEARS AGO WHERE IT WAS FCR OR BR AND NOW WE HAVE PEOPLE TAKING ONE PILL A DAY AND ENORMOUS IMPROVEMENT. THE STRIDES WE MAKE WITH RESEARCH AND CLINICAL TRIAL SO POWERFUL. WE CAN SIT HERE AND TALK ABOUT OUR TRIALS AND RESEARCH BUT ULTIMATELY IT'S ALL OF YOU WE NEED TO PARTICIPATE IN THE TRIALS BECAUSE WITHOUT THE PATIENTS, THE TRIALS CAN'T EXIST. MOVING FORWARD I LIKE MY SLIDE ON WHAT MAKES NIH UNIQUE. IT'S THE BENCH TO BENCH CONCEPT ADMIRAL CHILDS MENTIONED. IT'S REMARKABLE. GOING BACK TO THE FINANCIAL BARRIERS, I WOULD SAY, IT'S TRICKY TO DO RESEARCH IN THE COMMUNITY. WE'RE IN THIS EXTRAORDINARY POSITION TO DO THINGS THAT YOU CAN'T DO OUTSIDE BECAUSE IT'S FREE AND WE HAVE RESOURCE TO DO THE RESEARCH TO FIND OUT REALLY INVALUABLE DATA. INTERESTINGLY ENOUGH, JUST THE GEOGRAPHICAL WAY YOU HAVE LABORATORIES CLOSE TO PATIENT CARE AREAS. WE'RE ABLE TO DO THINGS THAT MAY BE IMPOSSIBLE IN THE COMMUNITY LIKE A RESEARCH LYMPH NODE BIOPSY. THAT PROVIDES SO MUCH GOOD INFORMATION BUT YOU HAVE BARRIERS WITH CO-PAYS AND INSURANCE WON'T COVER IT AND THE TIMING OF GETTING THE TISSUE TO THE PATHOLOGIST. IT JUST BOGGLES THE MIND WITH HOW MANY HICCUPS ARE IN THE SYSTEM AND PUSH THAT THROUGH TO GET GOOD DATA ON WHEN WE KNOW IS THE HOT BEDS OF CLL ACTIVITY. ANOTHER UNIQUE FEATURE DR. CHILDS MENTIONED IS EVERYTHING'S FREE. THIS IS THE POINT WHERE I LIKE TO MENTION THOUGH IT'S ALL FREE WHEN YOU GET HERE. WE REALLY LIKE TO COLLABORATE WITH YOUR COMMUNITY PHYSICIAN OR HEMATOLOGIST. IT'S IMPORTANT TO MAINTAIN THAT RELATION-TO WORK TOGETHER WITH THEM. WE LIKE TO SHARE NOTES WITH THEM AND GET THEIR NOTES. WE LIKE TO KEEP THEM IN THE LOOP AND BE KEPT IN THE LOOP. THERE MAY BE TIMES EVEN WHEN YOU'RE PARTICIPATING IN A CLINICAL TRIAL SAY YOU'RE FROM IDAHO AND NEED A CBC DONE BECAUSE YOUR COUNTS WERE LOW. IT'S NOT COVERED BECAUSE IT'S NOT NIH AND WE WANT YOU TO MAINTAIN INSURANCE AND SO WHY SHOULD YOU PARTICIPATE IN A CLINICAL TRIAL? LOOK AT OUR EXPERT TEAM. THEY'RE SO KNOWLEDGEABLE. IT'S WELL KNOWN PEOPLE WHO SEEK OUT HEALTH AND COUNSEL OF A SPECIALIST DO BETTER. YOU DON'T WANT TO GO TO AN ASIAN RESTAURANT TO GET REALLY REALLY GOOD SUSHI. WANT TO GO TO A JAPANESE RESTAURANT. YOU DON'T WANT TO GO TO A EUROPEAN RESTAURANT TO HAVE GOOD SPAGHETTI. YOU WANT AN ITALIAN RESTAURANT AND WHERE THE SPECIALTY LIES TO GET THE MOST CHANCE OF GETTING THE MOST INFORMATION AND HIGHEST LEVEL OF EXPERTISE ON YOUR CASE. ALSO, A CLINICAL CENTER PATIENT AND PEOPLE PARTICIPATING IN RESEARCH MAY HAVE ACCESS TO NEW TREATMENTS AN REGIMENTS THAT MAY NOT BE AVAILABLE IN THE COMMUNITY THAT COULD BE OF GREAT BENEFIT TO THEM AND PATIENTS ARE ALSO -- IT MAKES ME FEEL REALLY GOOD TO KNOW HOW MUCH PEOPLE SAY THEIR PARTICIPATION IS SO THEY CAN HELP PEOPLE IN THE FUTURE TO FIND OUT MORE ABOUT THE DISEASE AND HELP US HOPEFULLY GET TO THAT PLACE WHERE DR. CHILDS IS UP HERE SAYING THIS IS THE PLACE WHERE WE FOUND THE CURE FOR CLL. THIS IS A NICE MAP MY COLLEAGUE JUNS SOTO PUT TOGETHER. IT'S AN ILLUSTRATION OF THE PATIENTS PARTICIPATING ON OUR SINGLE AGENT IBRUTINIB STUDY. IT SHOWS HOW FAR PEOPLE COME TO PARTICIPATE IN TRIALS. WE DO PROVIDE TRAVEL SUPPORT FOR PEOPLE TO COME TO THE CLINICAL CENTER AND WE PROVIDE LODGING. IT ENABLES PEOPLE TO PARTICIPATE EVEN FROM AS FAR AS WASHINGTON STATE OR IDAHO. IT'S REMARKABLE HOW FAR PEOPLE WILL COME. WE HAVE PATIENTS THAT COME FROM CANADA AND STILL COME EVERY THREE MONTHS FOR THEIR FOLLOW-UP WHICH IS REALLY GREAT. HOW DO YOU FIND OUT ABOUT CLINICAL TRIALS? THERE'S TWO SITES I RECOMMEND. ONE SEARCH THE STUDIES. IT'S AN ONLINE DATABASE THAT SHOWS ALL THE RESEARCH TAKING PLACE HERE AT THE CLINICAL CENTER. YOU CAND FINAL CASH -- CAN FIND THINGS GEOGRAPHICALLY AND IF YOU WANT A TRIAL IN CINCINNATI, YOU CAN SEE WHAT'S GOING ON IN CINCINNATI. MAKING THE DECISION. I THINK IT'S TOUGH. I WATCH PEOPLE GO THROUGH THIS AND THEY ASK QUESTIONS AND FIGURE OUT IF THIS IS RIGHT FOR ME AND ULTIMATELY WE CAN PRESENT ALL THE INFORMATION IN THE WORLD BUT IT'S YOU WHO MAKES THE DECISION. IT'S REALLY IMPORTANT TO FIND OUT ALL THE RELATIVE INFORMATION. AS I MENTIONED, WHAT'S THE PURPOSE OF THIS STUDY? WHAT IS REQUIRED OF ME. THIS SAY BIG ONE BECAUSE WHEN -- IS A BIG ONE BECAUSE WHEN YOU ENROLL IN A CLINICAL TRIAL YOU'RE A PARTNER IN RESEARCH. WE WANT TO WORK TOGETHER TO GET THE BEST DATA POS AND BEST OUTCOME FOR YOU. YOU NEED TO KNOW MOI -- MY ROLE AND WHAT'S EXPECT OF ME AND WILL IT DIRECTLY BENEFIT ME? THAT'S SOMETHING TO CONSIDER AND WILL IT BENEFIT OTHERS. THAT COULD BE A DRIVING FORCE IN A LOT OF PEOPLE'S DECISIONS ABOUT PARTICIPATING IN RESEARCH. ALSO, ARE THERE RISKS? IT'S A STONNISHING TO ME AND YOU -- ASTONISHING TO ME AND YOU LISTEN TO A BENADRYL COMMERCIAL AND YOU HEAR ALL THE EFFECTS AND IN AN ALL RIGHT YOU'D WANT TO KNOW -- CLINICAL TRIALS YOU'D WANT TO KNOW ABOUT THE RISKS AND TALK ABOUT WITH YOUR DOCTOR AND FAMILY AND WE WANT TO BE PARTNERS IN THAT DECISION BUT YOU WILL MATLY ONLY YOU CAN MAKE THAT CHOICE. I END ON THIS SLIDE. IT'S BASICALLY A PLUG FOR NIH. THIS IS MYSELF AND SUSAN SOTO. WE ARE ALWAYS HERE TO HELP. IF THERE'S ANY QUESTIONS YOU HAVE, IF YOU'RE INTERESTED IN PARTICIPATING, IF YOU WANT MORE INFORMATION, YOU JUST CALL US AND WE WALK YOU THROUGH THE WHOLE SYMPTOM. I KNOW I JUST WONDERED OUT OF CURIOSITY IF YOU FEEL COMFORTABLE, HOW MANY HAVE PARTICIPATED IN ONE CLINICAL TRIAL? HOW MANY HAVE PARTICIPATED IN TWO? THREE? THAT IS REMARKABLE. REMARKABLE. SOME ARE VERY SAVVY CUSTOMERS AND SOME MAY NOT BE AND MAY BE INTIMIDATED BY THE PROCESS. IF SO, I'VE LEFT A BUNCH OF CARDS AT THE DESK AND IF YOU HAVE ANY QUESTIONS JUST COME AND FIND ME AT THE BREAK. OKAY. THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> THE TITLE LOOKS LIKE I'LL GIVE YOU A MENU OPTION IN POINTING THE NEW DISHES OR THE CHEF'S FAVORITE. I'LL DO THAT AND ALSO I'LL PUT THAT INTO THE CONTEXT OF SCIENCE IN NCLL. THE GOAL IS TO HELP YOU UNDERSTAND HOW WE DO RESEARCH AND HOW WE'LL CHANGE THE FIELD BY THAT RESEARCH. TO PUT OUR TRIALS INTO THE CONTEXT OF CLL, DRUG DEVELOPMENT, I'LL LOOK BACK ON THE PAST 60 YEARS. IN 1950, CLL PATIENTS HAD LIMITED TREATMENT OPTIONS. THEY HAD T.E.M., RADIATION AND THEN WE HAD DRUGS WE SOMETIMES USE FOR CLL PATIENTS TODAY. THEN OUR UNDERSTANDING OF CLL EVOLVED DRAMATICALLY SINCE THEN. NOW WE KNOW IT'S A COLLECTION OF DIFFERENT DISEASE BIOLOGIES AND MANY PATIENTS BEHAVE DIFFERENTLY FROM EACH OTHER. WE CAN TRY SO SUBSET THE PATIENTS BY CLINICAL STAGING OR GENETIC CHANGES. >> IN THE 1990s, RITUXIMAB ENTERED THE CLINICAL AND MANY WERE DEVELOPED AND THIS NEXT 10 YEARS WERE FOCUSSED ON MIXING AND MATCHING THEM INTO COMBINATION REGIMENTS. SOME MAY HAVE HEARD FCR AND BR. THESE ARE BASICALLY MIX AND MATCHING TWO OR THREE DRUGS TOGETHER FOR A LIMITED PERIOD OF TIME AND HOPE FOR THE BEST OUTCOME. SO WHAT IS THE OUTCOME? THEY TREATED 300 CLL WITH FCR A CHEMOTHERAPY REGIMENT AND SOME FOR A LONG TIME OF 12 YEARS. AND WITHIN THAT VERY LONG PERIOD OF FOLLOW-UP, ABOUT ONE-THIRD ACHIEVED ONGOING REMISSION. I WANT TO NOTE THAT IMAGINE PATIENTS GOING TEXAS TO GET FCR THERAPY. THEY'RE YOUNG, FIT AND VERY SELECTIVE PATIENTS WHO PARTICIPATED IN THE CLINICAL TRIAL AND THEY'RE OUTCOME IN THAT POPULATION WAS VERY GOOD IN ONE-THIRD OF THE PATIENTS. UNFORTUNATELY, FCR DIDN'T WORK FOR EVERYBODY. IN FACT, HALF THE PATIENTS CAME BACK WITH RELAPSED CLL AND SALVAGED CHEMOTHERAPY AND I IN SOME CASES IT WASN'T SO EFFECTIVE. SO WE HAVE TO DO BETTER AND THAT BETTER IDEA CAME FROM THE LAB AND THE SCIENTIFIC DISCOVERIES IN CLL. THE SLIDE SHOWS THE SURVIVAL SIGNAL IN THE CLL CELLS. THIS SHOWS THE SURFACE AND AT THE TAIL THERE'S YELLOW P WHICH MEANS THEY'RE ACTIVATING THEMSELVES AND IT LEADS TO THE SURVIVAL OF CLL CELLS. WITHIN THE ACTIVATION CASCADE, THERE'S A KINASE AND WE HAVE NOW DRUGS IN THE CLINICAL THAT CAN INHIBIT BTK. THESE DRUGS ARE CALLED BTK INHIBITORS AND ONE OF THE FIRST IS IBRUTINIB AND WE HAVE OTHERS IN THE CLINICAL AND ALSO FDA APPROVED FOR CLL. SINCE IBRUTINIB ENTERED THE CLINICAL, THE DRUG DEVELOPMENT CLOCK GOT FASTER THAN EVER. IN 2010, IBRUTINIB WAS TESTED IN THE LAB IN THE CELLS AND ANIMALS. THEN IN EARLY 2012, THE FIRST IN HUMAN STUDY LOOKING AT THE TOXICITY OF THE DRUG, THE PHASE 1 STUDY WAS CONDUCT. SHORTLY AFTERWARDS, PHASE II STUDY LOOKING AT THE ACTIVITY OF IBRUTINIB WAS TEST AND THEN LOOKING AT CLASSIC CLL THERAPY HEAD-TO-HEAD WAS CONDUCTED AND THAT'S CALL THE PHASE III TRIAL. THIS LED TO THE APPROVAL OF IBRUTINIB. FIRST IN PATIENTS WITH TREATMENT AND DELETION OF 17P IN CLL. THEN FDA EXPANDED THE APPROVAL SO ANY CLL PATIENTS REGARDLESS OF PRIOR TREATMENT STTS OR GENETIC -- STATUS OR GENETIC OR PREVIOUS STATUS CAN RECEIVE IT. WE ENROLLED 86 PATIENT TO TWO COHORT. DELETION 17P AND THOSE 65 AND OLDER. THE PIE CHARTS SHOW THE RESPONSE RATE OF BOTH COHORT. THE LIGHT BLUE AND DARK BLUE INDICATE BEST, PARTIAL AND COMPLETE RESPONSE AT THEIR BEST RESPONSE. YOU CAN SEE THE MAJORITY OF THE PATIENTS RESPONDED TO IBRUTINIB REGARDLESS OF DELETION 17P STATUS. IT'S NOTABLE WITH PATIENTS WITH DELETION 17P HAD A HIGH RESPONSE RATE TO IBRUTINIB BECAUSE THEY WERE CLASSICALLY KNOWN TO HAVE LOW RESPONSE RACE TO CHEMOTHERAPY. AS WE FOLLOW OUR PATIENTS LONG TERM, WE HAVE NOW REALIZED THAT IBRUTINIB RESPONSE HAS NOT BEEN THE SAME IN EVERY BODY WE REQUIRED A FIVE-YEAR FOLLOW-UP OF THE COHORT AND THE SURVIVAL CURVE BETWEEN PATIENTS WITHOUT - AND WITH DELETION 17P. IN PATIENTS WITH DELETION 17P, HALF PROGRESSED OR DIED AT FIVE YEARS COMPARED TO 20% WHO PROGRESSED OR DIED AT FIVE YEARS INDICATING PATIENTS WITHOUT DELETION 17P DID MUCH BETTER. WHEN WE JUST FOCUSSED ON PATIENTS WITH 17P WE SEE ANOTHER SEPARATION BASED ON THEIR TREATMENT STATUS. PATIENTS WITH PRIOR THERAPY IN THE RED LINE DROPPED OFF FASTER COMPARED TO PATIENTS WHO RECEIVED IBRUTINIB AS THE FIRST LINE THERAPY. THIS DATA INDICATES PATIENT S WITH DELETION 17P SHOULD AVOID CHEMO AND RECEIVE IBRUTINIB AT FIRST LINE THERAPY AND PATIENT WHO'S RECEIVE IBRUTINIB AS FIRST LINE DO WELL EVEN WITH DELETION 17P. SO WHAT HAPPENED IN PATIENTS WHO PROGRESSED AND WENT OFF STUDY? MANY PROGRESSED WITH CLL. SOME PROGRESSED WITH A TRANSFORMATION. WE STUDIED THE PATIENTS WHO PROGRESSED WITH CLL AND FOUND PATIENTS CAN ACQUIRE MUTATIONS THAT CONFER RESISTANCE AND BTK IS INHIBITED BY IBRUTINIB AND AFFECTS THE BINDING OF IBRUTINIB TO THE BTK AND THAT MAKES IBRUTINIB INEFFECTIVE IN THOSE PATIENTS. ANOTHER MECHANISM OF DRUG RESISTANCE IS AFFECTING THE DOWNSTREAM OF BTK REACTIVATING THE SIGNAL IN THE CLL CELLS. IN ADDITION TO DRUG RESISTANCE IT'S OTHER LIMITATIONS RELATED TO IBRUTINIB. RESPONSE SUCH AS RESIDUAL DISEASE NEGATIVITY IS UNCOMMON. IBRUTINIB IS GIVEN AS A CONTINUOUS THERAPY AND THAT INCREASES THE COST AND POTENTIALLY TOXICITY. THOUGH IT'S WELL TOLERATED IN GENERAL, IT HAS NOTABLE SIDE EFFECTS SUCH AS ATRIAL FIB FIBRILLATION AND MUSCLE AND JOINT PAIN AND BLEEDING. IT CAN INTERACT WITH WOLFERIN AND THAT CAN INCREASE THE TOXICITY. WE HAVE JUST THIS CAUSE THAT CHEMOTHERAPY WAS CONSIDERED A STANDARD OF CARE IN CLL AND IBRUTINIB HAS MANY LIMITATIONS. WE WANT TO OVERCOME THAT IN THE RESEARCH SETTING. AND AT THE NIH, OUR STRATEGY IS TO OVERCOME THAT LIMITATION IS TO USE ALTERNATIVE ORAL AGENT ENGAGE IMMUNE DEFENSE AND UNDERSTAND IMMUNE FUNCTIONS OF CLL PATIENTS AND IMPROVE THE QUALITY OF RESPONSE SO WE CAN EVENTUALLY STOP THERAPY. IN THE LATER PART OF MY TALK, I WILL GO THROUGH EACH STRATEGY ONE BY ONE AND LINK IT TO THE ONGOING OR UPCOMING CLINICAL TRIALS. AND THE OTHER IBRUTINIB HAS POTENTIALLY LESS SIDE EFFECTS. DR. SAHN IS LEADING THE PHASE II STUDY. IT WILL ENROLL 48 PATIENTS AND COMPLETE THE APPROVAL RECENTLY. THESE PATIENTS WERE RANDOMIZED TO EITHER OF THE TWO DOSING GROUPS. THE FIRST TO ACALABRUTNIB. THE TOTAL DOSE WAS 200 MILLIGRAMS PER DAY. YOU CAN SEE THE RESPONSE SIMILAR I BOTH GROUPS AND WHEN WE APPLIED STATISTICAL TESTING FOR THE RESPONSE RATE THERE WAS NO DIFFERENCE BETWEEN ONCE AND TWICE DAILY. IT WAS USED FOR DISEASE AND WE REVIVED THE STUDY SO PATIENTS SWITCH TO TWICE-DAILY DOSE AFTER SIX MONTHS. THE NEXT PART OF MY TALK WILL TALK ABOUT ENGAGING IMMUNE DEFENSE TO TREAT CLL CELLS. IN OUR IMMUNE SYSTEM THERE'S A KILLER CELL CALLED EFFECTER T CELLS. THEY RECOGNIZE NON-CELLS AND ATTACK THEM TO WE'RE NOT INVADED BY THE NON-CELLS BAD OUTSIDE ATTACKERS. AND THEY INVOLVE ANY INFECTION AND CANCER. IF THIS IS THE CASE, ONE MIGHT ASK, CAN WE USE INFECTION TO AWAKEN OUR IMMUNE SYSTEM SO THAT IT CAN KILL CANCER? IT SOUNDS CRAZY BUT PEOPLE TESTED IT AT THE CLINIC IN 19th CENTURY, DR. COLI AT NOW MEMORIAL KETTERING TESTED STREP STREPTOCACCAL BACTERIA AND THE TUMOR MELTED IN DAYS. HE TESTED THIS BACTERIAL TOXIN IN HUNDREDS OF PATIENTS AND HE ACTUALLY NAMED IT AFTER HIMSELF. UNFORTUNATELY, THE TOXIN WASN'T SO EFFECTIVE. IT HAD MODEST EFFECT AT BEST AND SOME PATIENTS DIED DUE TO INFECTION. SO WE NO LONGER GIVE LIVE BACK TEAR WAS TO TREAT CANCER AND WE USE IT TODAY TO TREAT PATIENTS WITH BLADDER CANCER. SO WHY DID COLLEY TOXIN FAIL? WHY DID THAT NOT CURE CANCERS? THE REASON IS THAT THERE IS A MECHANISM IN OUR BODY TO CONTROL THE KILLER T CELL. THOSE MECHANISM THE SIGNAL IN THE T CELLS AND IMMUNE SUPPRESSIVE CELLS IN THE IMMUNE MICROENVIRONMENT. BECAUSE OF THESE TWO MECHANISMS, THE KILLER T CELLS NO LONGER A KILLER. PEOPLE HAVE FOUND OUT THAT CANCER CELLS ACTUALLY EVOKE THE BREAK TO BE ON CONSTANTLY. AND THAT MAKES THE CANCER CELL TO PROLIFERATE AND AVOID THE ATTACK FROM THE EFFECTIVE T CELLS. SCIENTIST HAVE FOUND OUT THERE IS A BREAK MECHANISM IN CANCER CELLS AND MANY DOCTORS AT KYOTO UNIVERSITY FOUND THE BREAK MOLECULE ON T CELLS. THIS IS AN IMPORTANT DISCOVERY BECAUSE WE USE THE CONCEPT TO RELEASE THE BREAK AND TREAT CANCER AND THAT TREATMENT IS CALLED IMMUNE CHECKPOINT INHIBITION. PROBABLY THE MOST FAMOUS TREATED WITH THIS IS A FORMER PRESIDENT JIM YO CARTER WHO WAS -- JIMMY CARTER WHO WAS DIAGNOSED WITH METASTATIC MEL KNOW -- MELANOMA AND HE'S NOW DOING WELL AND 94 YEARS OLD. WE'D LIKE TO ENGAGE IMMUNE DEFENSE FOR CLL TREATMENT AND WE LAUNCHED TWO TRIALS CENTERED AROUND THIS CONCEPT. THE FIRST TRIAL USING TWO DRUGS. FIRST IS THE IBRUTINIB WHICH TARGETS THE CLL CELLS AND THE SECOND DRUG IS ONE TO ROW MOVE THE IMMUNE SUPPRESSIVE ENVIRONMENT AND AT THE SAME TIME TREAT CLL CELLS. THE SECOND TRIAL USING IBRUTINIB AS A BACKBONE AND RELEASE THE BRAKE SIGNAL ON T CELLS AND I'LL WAKE YOU THROUGH EACH ONE BY ONE. WE FIRST LAUNCH THE TRIAL USING IBRUTINIB IN COMBINATION IN PREVIOUSLY UNTREATED CLL PATIENTS. OF THE PATIENTS RECEIVING IBRUTINIB ONCE A DAY AND THE FLUDARABINE AND 11 PATIENT HAVE REACHED TWO YEARS ON THE STUDY. DARK AND LIGHT BLUE INDICATE PARTIAL RESPONSES AND RED BAR IS THE COMPLETE RESPONSE. AND THE RESPONSE GOT BETTER OVER TIME LIKE WINE. WHEN WE COMPARED THE RESULT TO OTHER STUDIES USING IBRUTINIB ONLY WITHOUT FLUDARABINE YOU SEE THE RESPONSE IN THE TRIAL. BEING ENCOURAGED BY THE TRIAL WE TOOK IT TO THE NEXT LEVEL AND ADDED THE THIRD AGENT WHICH WORKS TO RELIEF THE BREAK IN THE T CELLS. THIS IS FOR HIGH-RISK PATIENTS. AND IT'S TAKEN DAILY AS A CONTINUOUS THERAPY AND GIVEN OVER ONE CYCLE AND THE OTHER IS GIVEN OVER ONE YEAR IN THREE-WEEK INTERVALS. AFTER THAT THEY RECEIVED IBRUTINIB ONLY. THE FIRST CRITERION WAS THE STUDY THERAPY HAVE TO BE THE FIRST ONE THE PATIENT RECEIVED AND THE SECOND IS THE PATIENT SHOULD HAVE NEGATIVITY IN TWO YEARS AND THE STUDY STARTED IN 2017 AND WE'RE RECRUITING NEW PATIENTS. WHAT DO I MEAN BY HIGH RISK CLL WHEN IBRUTINIB IS WORKING WELL. WE ANALYZED OVER 600 PATIENTS TREATED WITH IBRUTINIB AT THE NIH AND THE OUTSIDE STUDIES OUTSIDE THE NIH. WE IDENTIFIED PATIENTS WITH INFERIOR OUTCOME. 30% OF THE PATIENTS IN THE DATA SET HAD ALL THREE FACTORS AND WE NAMED THEM HIGH RISK GROUP. WHEN WE COMPARED THE HIGH RISK GROUP TO OTHER PATIENTS WITH TWO OR ONE OR ZERO RISK FACTORS, THERE WAS A SIGNIFICANT DIFFERENCE IN TERMS OF HOW FAST THEY PROGRESSED ON IBRUTINIB THERAPY. AT THREE YEARS, HALF THE PATIENTS IN THE HIGH RISK GROUP PROGRESSED OR DIED COMPARED TO 15% IN THE LOW-RISK GROUP. IN FACT, THE LOW-RISK GROUP WAS WELL SERVED ON IBRUTINIB MONOTHERAPY. I'M GOING TO SWITCH AND TALK ABOUT UPCOMING TRIALS USING NOVEL AGENT. THERE'S A BCL2 INHIBITOR. WHAT IT DOES IN THE CLL CELLS IT HOLDS ON TO A SIGNAL WHICH MAKES CLL CELLS ALIVE AND HAPPY. YOU CAN SEE BCL2 IS A BAD SIGNAL FOR CLL CELLS. IT BINDS AND RELEASES THAT SIGNAL AND MAKES THE CLL CELLS DIE. IT'S TAKEN ONCE A DAY AND APPROVED FOR CLL PATIENTS WITH PRIOR THERAPY. THE LIMITATION OF IS IT CAUSES TUMOR LIKE SYNDROMES. AND IT'S BASICALLY A RAPID BREAK DOWN OF THE CANCER CELL THAT RELEASE THE TOXIC METABOLITES WHICH CAN CHANGE THE HEART RHYTHM, KIDNEY FUNCTION AND SOMETIMES CAUSE DEATH. SO IT'S A FATAL CONDITION. AND TO OVERCOME THAT LIMITATION VENETOCLAX WAS STARTED IN LOW DOSE AND RAMPED UP WEEKLY OVER TIME AND DURING THAT RAMPING UP PERIOD, PATIENTS SHOULD UNDERGO CLOSE MONITORING. SO AT THE NIH, WE WILL STUDY THE VENETOCLAX RAMP UP STARTING AT 20 MILLIGRAMS IN THE FIRST WEEK AND RAMPED UP PROGRESSIVELY OVER THE NEXT FIVE WEEKS UNTIL THE PATIENT REACHES THE FULL DOSE OF 400 MILLIGRAMS. THE VENETOCLAX WILL BE PROVIDED AT NIH ALONGSIDE THE DRUG AND MONITORING. AFTER WEEK FIVE, THE VENETOCLAX PRESCRIPTION WILL BE SENT TO YOUR OWN ONCOLOGIST. CAN GET IT FROM THE GET GO FROM YOUR OWN DOCTOR, WHY DO YOU HAVE TO STUDY IT AT THE NIH? THE REASON IS THAT THE RAMP UP REQUIRES FREQUENT MONITORING AND SOMETIMES HOSPITAL ADMISSIONS. WE OFFER THIS RAMP UP AS A SERVICE TO THE OUTSIDE HEMATOLOGIST. AT THE SAME TIKE, WE WOULD LIKE TO STUDY, HOW GENETIC COMPONENTS OF CLL CHANGE OVER TIME DURING THE RAMP UP WHICH HAVE NEVER BEEN STUDIED OUTSIDE. THE SECOND UPCOMING STUDY USES A DELTA AND GAMMA INHIBITER WHICH INHIBITS THE SURVIVAL IN CLL CELLS AND ALTERS THE IMMUNE MICRO ENVIRONMENT. IN THE LAB, IT HAS SHOWN ACTIVITY AGAINST IBRUTINIB RESISTANT CELLS AND TAKE THE NEW DRUG FOR THOSE WHO DEVELOP RESISTAN RESISTANCE OR THOSE WHO CONFIRM RESISTANCE TO IBRUTINIB. WE LOOK AT IBRUTINIB FOR THREE MONTHS. THE REASON IS WE HYPOTHESIZE THE OVERLAP CAN HELP PREVENT ACCELERATION OF CLL AND REDUCE IMMUNE-RELATED SIDE EFFECTS. FROM THIS STUDY WE'D LIKE TO DEVELOP IF IT'S EFFECTIVE AND WHETHER IT CAN AFFECT THE MICRO ENVIRONMENT. SO IN CLOSING, I WOULD LIKE TO THANK YOU FOR YOUR ATTENTION AND ESPECIALLY THANK OUR PATIENTS WHO PARTICIPATED IN OUR STUDY BECAUSE THEY DONATED LOTS OF BLOOD SAMPLES AND BONE MARROW SAMPLES AND LYMPH NODE SAMPLES AND A PROCEDURE TO COLLECT CLL CELLS. AND WE HAVE LEARNED A LOT AND WOULD LIKE TO IMPROVE CLL THERAPY SO OUR PATIENTS CAN LIVE LONGER AND HAVE A BETTER QUALITY OF LIFE. THANK YOU. >> HELLO. LIKE ANY EVENT THAT INVOLVES DOCTOR WHETHER IT'S AN APPOINTMENT OR MEETINGS, NO SURPRISE, WE'RE RUNNING A LITTLE BIT LATE. SO WE'LL TRY TO CATCH UP. WE MAY PUSH THE REFRESHMENTS AN STUFF TO LATER AND SHORTEN IT UP. I ALWAYS LIKE TO START BY THANKING YOU. THANK YOU FOR COMING. THANK YOU TO THE NIH AND THE TEAM THAT'S HERE. I ALSO WANT TO THANK THE SPONSORS FOR THE CLL SOCIETY PORTION OF THIS. TO THE NIH PROVIDES THE FACULTY AND THE ROOM AND THE SUPPORT AND WITHOUT THEIR HELP WE WOULDN'T BE ABLE TO DO THIS AS A NOT FOR PROFIT. DOCTORS START WITH THEIR DISCLOSURES. I'M GOING IT TALK ABOUT THE FACT I WAS ON A CLINICAL TRIAL. YOU SAW ABOUT THOSE CLINICAL TRIALS. AND I WAS ON A DRUG THAT JUST HAD A NUMBER AND WHEN DO YOU THE MATH, I'VE BEEN ON THE DRUG SEVEN YEARS SO I WAS IN A PHASE 1 TRIAL OF THE GAME CHANGING DRUG IBRUTINIB. I HAVE NO CLL IN MY BLOOD BECAUSE OF THE SECOND TRIAL AND I'LL EMPHASIZE THAT IN THE INTEREST OF TIME. I HAVE A BIAS TOWARDS EXPERT CARE AND NOVEL THERAPIES AND CLINICAL TRIALS AN PATIENT INVOLVEMENT. MY LEARNING OIFBJECTIVES IS TO TALK ABOUT MY CASE AND I'LL GO OVER THE FIRST PART QUICKLY. I TALK FAST. WE'LL TALK A LITTLE BIT ABOUT SHARED DECISION MAKING. WE'LL LEARN TIPS ON BEING YOUR OWN ADVOCATE AND TRY TO INCREASE OUR ODDS OF BEING ALIVE. YOU CAN READ WHAT I DID TO STAY ALIVE BUT THAT WAS A PORTRAIT MY SON PAINTED OF ME EARLY ON WHEN I WAS FIRST DIAGNOSED. I HAD FACIAL HAIR TO HIDE MY ENLARGED NYMPH NODES BECAUSE MY PATIENTS SAID WHAT'S GOING WITH THE NODES. SO THAT WAS TO TRY TO HIDE THOSE. THINGS DID NOT LOOK GOOD FOR ME AND I'LL SHOW YOU THE CURVING THERE. NOW IT HANGS IN OUR DINING ROOM AS A REMEMBRANCE OF A DIFFICULT TIME IN MY LIFE. IT WAS THERE AT FIRST IT WAS A WAY OF REMEMBER DAD WHEN HE'S GONE BUT I'M HERE 13 YEARS LATER. SO WE TALK ABOUT ALL OF US PATIENTS AND CAREGIVERS. WE WENT THROUGH THE DEER IN THE HEADLIGHTS AND IT'S LIKE, I'M FINE, CLL IS BORING WHEN YOU LOOK AT IT IN THE MICRO SCOPE AND I'M VERY GLAD ADMIRAL CHILDS TALKED ABOUT PARADIGM SHIFT BECAUSE I'M GOING TO TALK ABOUT THAT A LOT IN THE DIAGNOSIS AS A PARADIGM SHIFT AND THE FIRST OF MANY. YOU HEARD THESE PROGNOSTIC FACTORS. THEY'RE ALL BAD THINGS TO HAVE. YOU KNOW WHAT THE CAP LINE MYER CURVE IS. WHEN YOU SEE THE CURVES FIRST LOOK AT THE DATE. WHEN I FIRST STARTED THERE WAS NOTHING OUT THERE. THE ONLY THING YOU SHOULD LOOK AT IS SURVIVAL WAS NOT SO GOOD IN THE 1990s. IT WAS BETTER IN THE '20s AT THE TURN OF THE NEW MILLENNIA. EVERY DECADE THE SURVIVAL GETS BETTER AND BETTER. CURVE BASED ON OLD THERAPIES AND ALWAYS LOOKING BACKWARDS BY DEFINITION, THEY CAN'T LOOK FORWARDS. THESE WERE MY ODDS, 5% TO BE AROUND. I PROGRESSED WITH ENLARGED NODES. GREW THIS LARGE SANTA CLAUS BEARD AND I ATTACKED MY OWN PLATELETS. I'LL SKIP THIS QUESTION BECAUSE I LOOKED PREGNANT BUT IT HELP MY CLL. I WENT FOR A FIRST REMISSION TRANSPLANT. BACK IN THE DAYS THE TRANSPLANT WAS THE ONLY OPTION. I WAS E-MAILING MY FRIENDS AND FAMILY ABOUT MY TRANSPLANT AND MY SON SAID THAT'S SO OLD SCHOOL AND SAID WHY DON'T YOU START A BLOG. I STARTED A BLOG AND TELLING WHAT WAS HAPPENING WITH THE TRANSPLANT. IT BECAME QUITE POPULAR. HERE'S A PICTURE MY SON DID AND DR. CHILDS WOULD AGREE THERE'S STILL A SMALL ROLE FOR IT BUT WE HAVE SO MANY NEW THERAPIES WE NO LONGER HAD THE TRANSPLANT AND I HAD A TRANSPLANT AT THE CITY OF HOPE AND I LOST ALL MY HAIR FROM THE CHEMOTHERAPY CONDITIONING. THERE WAS THIS CRACK IN THE BIOLOGY. SO THE B CELLS WHERE OUR CANCER COMES FROM ARE PART OF THE IMMUNE SYSTEM AND THEY HAVE TO COMMUNICATE WITH OTHER CELLS. THAT'S THEIR WHOLE PURPOSE TO LIVE. IF YOU BLOCK THEIR COMMUNICATION AND THE ANTENNAS THAT BREAK OFF THERE'S NO REASON TO LIVE. AND THEY DIE OF LONELINESS AND IT'S THE B CELL RECEPTOR. LIKE TAKING YOUR TV ANTENNA AND BREAK ICT. THEY HAVE NO BREAKING IT. THEY HAVE NO REASON TO LIVE AND THIS IS THE BROAD OPTIMISM AND EVERYONE WAS EXCITED AND AT THIS POINT THERE WAS A COUPLE DOZEN PATIENTS WITH THE NEW DRUGS IBRUTINIB AND CAL -- ACALABRUTINIB AND YOU HEARD ME SAY I'M ALIVE TODAY BECAUSE I WAS IN A CLINICAL TRIAL. I GOT SEVEN YEARS OUT OF IBRUTINIB. THERE'S LIES, DAMN LIES AND STATISTICS. I BEAT THE ODDS THOUGH I'M 17P DELETED AND I GOD SEVEN YEARS OUT OF IT. I HAVE SOME OF THE SIDE EFFECTS AND DEVELOPED THE MUTATION THAT LED TO A SLOW RELAPSE BUT GAVE ME ANOTHER SEVEN YEARS TO GIVE ME ANOTHER TIME TO PUSH TO THE NEXT THING AND THIS IS THE TRIAL I DIN. IT WITH A BIT JUST FOR CLL PATIENTS BUT I WAS THE 36th CLL PATIENT TO ENTER THE TRIAL. I'M NOT GOING TO GO THROUGH EVERYTHING IN IT BUT I'LL REFER TO YOU CLL SOCIETY.org AND LEARN ABOUT CAR T OUR HERO. HEARD WITH THE IMMUNE SYSTEM AND HOW THE CANCER CELLS ARE VERY SMART AT ESCAPING THE IMMUNE SYSTEM. SO WHAT THE SMART SCIENTISTS AND THIS WORK WAS PIONEERED HERE AT THE NIH. THE EARLY WORK ON USING THE IMMUNE SYSTEM. THE EARLY WORK ON CELLULAR THERAPY AND WE HAVE A GENERATION OF THINGS THAT WILL WORK. THEY TAKE AN EXHAUSTED T CELLS THAT DOESN'T DO A GOOD JOB OF WORKING AGAINST YOUR CANCER THAT'S GROWN WITHIN US AND TURNS IT INTO A SUPER HERO THAT'S LIKE AN ATTACK AND DESTROY. SO THE T CELLS ARE TAKEN OUT OF YOU AND GENETICALLY MODIFIED USING A VIRUS THAT'S A COUSIN TO AN AID'S VIRUS TO RECOGNIZE MARKERS ON TO THE CLL CELLS TO ATTACK THEM. THEY GO INTO A KILLING PHASE. IT'S A KILLING FRENZY THAT GOES ON. THERE'S MUCH MORE ON OUR WEBSITE. IT'S EASY TO FOLLOW BUT SOMETIMES THEY CAN OVER DO IT BECAUSE THEY ALSO KILL THE NORMAL B CELLS. I GOT EXTREMELY SICK FOR THIS. THEY RELEASE THESE CHEMICALS AND THE CELLS COMMUNICATE WITH CITE CYTOKINE AND IT'S CYTOKINE RELEASE KINDROME AND IT'S LIKE THE FLU TIMES THE FLU. I WAS GETTING PAIN MEDICATIONS AN HALLUCINATING AND FOR MY WIFE AND ADULT CHILDREN WATCHIN ME GO THROUGH THIS IS MUCH MORE DIFFICULT. I DON'T THINK CAREGIVERS GET ENOUGH CREDIT. CAN'T GO THROUGH THIS WITHOUT A CAREGIVER TAKING CARE OF YOU. IT MADE ME QUITE SICK. I HAD A LOT OF SYSTEMIC TYPE PROBLEMS. BUT THEY HAVE DRUGS STEROIDS AND OTHERS THAT CALMED THINGS DOWN AND I BEGAN TO FEEL BETTER. THE GOOD NEWS IS HERE WHEN I WAS RESTAGED ONE MONTH AFTER MY CAR-T THERAPY, THEY FOUND BY LOOKING AT MY BONE MARROW WHICH WAS ABOUT 60% FULL OF CLL WHEN I STARTED, THAT USING VERY SOPHISTICATED NEXT-GENERATION SEQUENCING DOWN TO 1/100,000 OR 1/1,000,000 CELLS THERE WAS NO TRACE AND ALL MY LYMPH NODES WENT BACK TO NORMAL. THIS IS AS GOOD AS IT COULD GET. I WAS UNDETECTABLE DISEASE IN THE BLOOD AND RECHECKED AT 11 MONTHS AND I STILL AM U MANY OF RD IN THE BLOOD. I DIDN'T HAVE BONE MARROW DONE. I HAD PERSISTENT CAR-T CELLS STILL PLAYING WHACK-A-MOLE WITH MY CANCER SIX MONTHS OUT. THIS IS -- NOW, NOT EVERYBODY'S AS LUCKY AS I AM BUT THIS IS A POTENTIAL THERAPY. I FAILED THE BONE MARROW TRANSPLANT AND 17P DELETE AND I FAILED IBRUTINIB SO THIS IS HELPFUL FOR ME. I STARTED TO TELL MY STORY. I START THE BLOG AND SPOKE AT MEETINGS WHERE CLL EXPERTS ARE LIKE DR. REISNER. WE SET UP THE CLL SOCIETY.org AND JUST ENTERING OUR FOURTH YEAR. WE'RE NOW HAVING ABOUT 50,000 PAID VIEWS A MONTH. I DIDN'T KNOW THAT WERE THAT MANY CLL PEOPLE IN THE WORLD READING THE WEBSITE. AS A PHYSICIAN YOU HAVE A RESPONSIBILITY. LOOK IN THE MIRROR. THIS IS OUR WEBSITE. IF YOU HAVEN'T VISITED, PLEASE VISIT. OUR MOTTO IS SMART PATIENTS GET SMART CARE. WE HAVE TOOLS SO IF YOU HEAR THINGS LIKE FCR OR BR, THEY'RE THERE FOR YOU. WE HAVE AN EXCEL SPREAD SHEET THAT EXPLAINS EVERYTHING TO FOLLOW YOUR LABS AND HAVE A LIST OF DOCTORS AND HAVE A THING OR PUTTING THINGS TOGETHER AND WE HAVE 33 SUPPORT GROUPS. YOU'LL HEAR FROM OUR LOCAL SUPPORT GROUP SO PLEASE STAY AND HAVE THAT. WE HAVE EDUCATIONAL FORUMS LIKE THIS A DOZEN A YEAR. WE HAVE AN ONLINE NEWSLETTER AND LOOKING FOR WRITERS. WRITE ABOUT YOUR EXPERIENCE WHETHER IT WAS A CLINICAL TRIAL OR DEER IN HEADLIGHTS FIRST MOMENT. WHAT IT WAS LIKE FOR YOU AS A PATIENT OR CAREGIVER. IT'S SO VALUABLE. THERE'S THINGS ONE PATIENT CAN TELL ANOTHER NOBODY ELSE CAN. PLEASE APPROACH ME, B FOR BRIAN, COFFMAN, -O-F-F-M-A-N AND WE HAVE HELP FOR PEOPLE WHO DON'T HAVE INSURANCE BECAUSE THERE'S A SURVIVAL ADVANTAGE TO SEEING A CLL EXPERT AND WE HAVE HIPAA CLIENT EXPERTS TO SPEAK TO ONLINE AND IF YOU ARE INTERESTED, THIS IS A TOOL KIT. SOMETHING TO TAKE TO YOUR COMMUNITY HEMATOLOGIST, WE'LL PASS OUT AT THE BREAK AND THE COMMUNITY HEMATOLOGIST CAN ORDER THIS FROM US USING THIS CARD AND IT HAS 10 PAGES ON THINGS LIKE WHAT IS CLL. WHAT IS THE STAGING? WHAT ARE THE APPROVED TREATMENTS? WHAT FUNDING IS THERE TO HELP ME PAY FOR MY MEDICATIONS. WHAT DOES THE SPLEEN DO? WHAT'S THE LYMPH NODE? ALL KINDS OF QUESTIONS TO HELP. THESE ARE TO GIVE TO THE DOCTORS TO GIVE TO THE PATIENTS. IF YOU'RE INTERESTED IN THAT, PLEASE DO THAT. WE HAVE ONLINE WEBINARS. I'LL NOW SWITCH TO TALK ABOUT BEING AN ADVOCATE AND HOW TO SAVE OUR OWN LIVES AND MAYBE THE LIVES OF OTHERS. ADVOCATING FOR YOURSELF AND ADVOCATING FOR OTHERS, THERE'S NO SPACE IN BETWEEN. SO THE FIRST THING YOU NEED TO KNOW IS YOU NEED TO KNOW YOURSELF WHEN YOU DO THIS. YOU NEED TO KNOW WHAT'S IMPORTANT TO YOU IN TERMS OF HANDLING YOUR CLL. YOU NEED TO KNOW WHAT YOUR BOTTOM LINE IS. ARE YOU THE KIND OF PERSON WHO NEEDS SIX MONTHS AND DONE AND DON'T HAVE TO THINK BIT OR TAKE A PILL THE REST OF YOUR LIFE? THAT'S AN IMPORTANT PIECE OF KNOWLEDGE AND MAY PUSH YOU IN ONE DIRECTION. YOU HAVE TO KNOW WHAT YOU'RE COMORBIDITIES ARE. IF HAVE YOU KIDNEY DISEASE, LIVER DISEASE, A BAD GUT. IT'S IMPORTANT TO KNOW YOU HAVE TO SHARE WITH YOUR CLINICIAN. YOU HAVE TO KNOW YOURSELF. YOU HAVE TO KNOW BEYOND YOURSELF AND WHAT'S YOUR CANCER MANAGEMENT AND WHAT INSURANCE COVERS AND WHAT THE FINANCES ARE, WHAT'S AVAILABLE AND YOU HEARD WITH THE CAL -- ACALABRUTINIB TRIAL AND YOU HAVE I SAY YOU WANT TO BE ASSERTIVE BUT NOT OBNOXIOUS. THERE'S A FINE LINE BETWEEN THE TWO. THE MOST PRECIOUS COMMODITY IS TIME AND DOCTOR'S TIME IS VERY LIMIT. I SAY START WITH YOUR MOST IMPORTANT QUESTION FIRST FOR YOUR PROVIDER. DON'T BRING IT UP AS THEY'RE WALK OUT THE DOOR. BRING IT UP AT THE BEGINNING OF YOUR MEETING WITH THEM. WHAT'S REALLY BOTHERING YOU. EVEN IF YOU'RE NERVOUS ABOUT IT. STATE YOUR POINTS CLEARLY, BE BRIEF AND CONCISE. YOU'LL GET FURTHER WITH THE PHYSICIAN. DOCTORS DON'T MIND IF YOU BRING IN REPORTS AND LABS AND PAPERS AND STUDIES. THE FACTS OVER THE OPINIONS. WE LIKE THAT. A SHARED-DECISION MAKING MODEL IS WHAT EVERYBODY WANTS AND WHAT WE'RE LOOKING AT IS THE DOCTOR WOULD PROVIDE THE INFORMATION. THE PATIENT WOULD BRING THEIR VALUES AND PREFERENCES AND TOGETHER YOU'D MAKE A PLAN. BUT NOW IT'S THE DOCTOR, THE NURSE, THE PHARMACIST, THE ONLINE WEBSITE, THE LEUKEMIA LYMPHOMA WEBSITE AND YOU GO BACK TO YOUR HEMATOLOGIST AND YOU SAY I HEARD ABOUT THIS BREAK WHERE THEY'RE UNLEERING THE -- UNLEASHING THE BRAKE. IT'S NO LONGER THE PROVIDER BUT A NETWORK OF INFORMATION PEOPLE GET THAT COMES INTO HOW YOU GET THE INFORMATION. WHAT MEDICAL EVIDENCE IS OUT THERE AND THEN YOU BRING YOUR PREFERENCES TO THAT AND MAKE A DECISION. HERE ARE MY COMMANDMENTS ON HOW TO LIVE. WE TALKED ABOUT BUILD TEAM. THIS IS A CRITICAL FIRST STEP, OKAY. YOU WANT TO KNOW WHO'S ON YOUR TEAM. IF YOU REMEMBER, ON MY FIRST SLIDE I FIRED DOCTORS BECAUSE THEY WEREN'T UP TO DATE ON CLL. CLL IS A RELATIVELY RARE CANCER. 25 BREAST CANCERS FOR EVERY CLL PATIENT AND THE PHYSICIAN CAN'T ALWAYS BE UP ON LITERATURE AND YOU ALWAYS HAVE TIME IN CLL BUT NOT FOREVER SO YOU HAVE TO MAKE DECISIONS BUT YOU DON'T HAVE TO RUSH THEM. UNDER REACT. YOU'LL GET GOOD NEWS AS WELL AS BAD NEWS. CONTROL IS AN ILLUSION. THINGS HAPPEN. ALL ACTIONS AN INACTIONS HAVE THEIR SIDE EFFECTS. THIS NUMBER ONE IN BOLD IS THE MOST IMPORTANT THING I THINK YOU HAVE TO THINK ABOUT, YOU SPLAY TO MAKE DIFFICULT DECISIONS WITHIN PERFECT KNOWLEDGE OF CONTRADICTORY ADVICE. I'LL SAY IT TWICE. MAY NEED TO MAKE DIFFICULT DECISIONS WITHIN PERFECT KNOWLEDGE AND CONTRADICTORY ADVICE. WE DON'T KNOW WHAT'S GOING ON. THAT'S WHY THERE'S CLINICAL TRIAL. SHOULD I TAKE COMBINATION THERAPIES OR ONE DRUG OR TWO OR CHEMO IMMUNO THERAPY? WE DON'T KNOW. SO THAT'S WHY CLINICAL TRIALS ARE THERE. THAT'S WHY WE NEED THIS STUFF. ABSOLUTELY, YOU HAVE TO THINK OUTSIDE THE BOX. YOU HAVE TO JOIN A SUPPORT GROUP. WE'LL BE TALKING ABOUT THAT AND REMEMBER TO STAY FORWARD AND STAY STRONG. WE'RE ALL IN THIS TOGETHER. WE DID A SURVEY. THE LARGEST EVER OF CLL PATIENTS, 1147 PATIENTS. WE PRESENTED THIS DATA AT THE AMERICAN SITE OF CLINICAL ONCOLOGY AND AT THE ASH MEETING YOU JUST TALKED ABOUT AND OUR TAKEAWAY IS THAT PATIENTS PREFER IN ONE OF OUR PRIOR STUDIES IT WAS 96% OF PATIENTS PREFERRED NON-CHEMOTHERAPY APPROACHES. IT SHOULD BE RESERVED FOR A SMALL GROUP OF PATIENTS WHERE IT'S POTENTIALLY CURATIVE. I THINK THE FUTURE IS THAT OUR TO THERAP -- CURING THERAPIES ARE AVAILABLE. AND THINGS LIKE THE CAR-T THERAPY. THAT WAS MY LEARNING OBJECTIVES. I WENT THROUGH A CASE AND TALKED ABOUT AN ONLINE SURVEY HOW WE MAKE DECISIONS AND I TALKED ABOUT SHARED-DECISION MAKING. I TALKED ABOUT PRACTICAL TIPS AND HOPEFULLY TO INCREASE YOUR ODDS OF STAYING ALIVE WITH CLL. AFTER THE BREAK, WE'LL HAVE A Q&A BUT TWO THINGS FIRST. AFTER THE BREAK, WE'RE GOING BE PASSING OUT REMEMBER TO ASK ME IF YOU WANT ONE OF THESE TOOL KITS. WE'LL PASS AROUND THE SEATS THE ENVELOPE IF YOU CAN SUPPORT THE CLL WE'RE A 5013C NON FOR PROFIT. YOUR HELP KEEPS US AND ALLOWS US TO DO THIS AND TO COME BACK AGAIN TO DO THIS AND THOUGH THE NIH IS SUPPORTIVE, WE'RE DEPENDENT ON INDIVIDUALS. IF YOU'RE WATCHING ONLINE ON THE VIRTUAL GO TO THE WEBSITE AND THERE'S A DONATE BUTTON THERE. THE SECOND IS, AND I'VE HEARD NEWS THAT THERE'S A BIG BIRTHDAY COMING UP NEXT WEEK. I KNOW THERE'S SOME PATIENTS HERE WHO HAVE A LITTLE SURPRISE FOR THIS BIRTHDAY COMING UP NEXT WEEK. SO IT'S AN 11-YEAR BIRTHDAY AND IT'S NOT FOR AN INDIVIDUAL. IT'S FOR I'VE BEEN IN THE TRIAL EIGHT YEAR AND I DECIDED TO SAY HAPPY BIRTHDAY AND THANK THE DOCTORS DIRECTLY WITH A LITTLE CAKE AND REICH MOST THINGS WE HAVE A COHORT WE HAVE TWO TYPES OF CAKE AND A BIRTHDAY CARD FOR BRIAN TO SIGN AND TWO OUT THERE FOR EVERYBODY TO SIGN AND THANK THE DOCTORS AND THE SUPPORT STAFF THAT HAVE BEEN WONDERFUL THROUGH THE YEARS. THANK YOU VERY MUCH FROM EVERYONE HERE. >> WE'LL HAVE A BREAK BUT BEFORE THE BREAK WE'LL HAVE A Q&A. I'LL ASK ALL THE PRESENTERS TO COME TO THE FRONT AND ASK THE QUESTIONS BECAUSE THIS IS BEING LIVE STREAMED, YOU'LL HAVE TO WALK OVER TO THE MICROPHONE AND I'LL JUST POINT TO PEOPLE >> HAVE THE SLIDES PRESENTED WILL THEY BE AVAILABLE FOR US AND WHERE AND HOW DO WE GET THEM? >> THE PLAN IS TO ARCHIVE THIS MEET. I DON'T KNOW ABOUT THE SLIDES YET BUT WE'LL SEE IF WE CAN WORK WITH THE HIP TO GET THE -- NIH TO GET THE SLIDES BUT THE ENTIRE MEETING WILL BE ARCHIVED SO YOU MAY HAVE TO LISTEN TO MY BAD JOKES AGAIN TO GET ANY SLIDES BUT IT TAKE US A WHILE TO DO THAT BECAUSE OF FORMATTING AND THAT STUFF.Y SLIDES BUT IT TAKE US A WHILE TO DO THAT BECAUSE OF FORMATTING AND THAT STUFF.Y SLIDES BUT IT TAKE US A WHILE TO DO THAT BECAUSE OF FORMATTING AND THAT STUFF.MY SLIDES BUT IT TAKE US A WHILE TO DO THAT BECAUSE OF FORMATTING AND THAT STUFF. >> HOW DO YOU HELP PATIENTS MAKE THE RIGHT DECISION? HOW DO YOU LOOK AT THE IMPACT OF THINGS LIKE GENETIC MAKEUP OR SOCIAL DETERMINATES OF HELP OR HELP SHAPE BETTER DECISIONS FOR THE PATIENT AND THEIR CAREGIVERS? >> THE FIRST THINK YOU NEED TO DO IS HAVE AN EXPERT ON YOUR TEAM OR BECOME AS EXPERT AS YOU CAN. I ALSO THINK IT'S IMPORTANT TO HAVE A SUPPORT GROUP OF OTHER CLL PATIENTS WHO CAN GIVE YOU ADVICE ABOUT WHAT'S GOING ON BECAUSE YOU CAN'T BE TALKING TO YOUR FAMILY ALL THE TIME ABOUT THIS IS WHAT I'M GOING THROUGH THEY DON'T GET IT AND YOU BECOME A BURDEN TO THEM BUT OTHER PATIENTS COMPLETELY GET IT AND THAT'S THE BIG ADVANTAGE TO SUPPORT GROUPS. YOU ALSO HAVE TO LIVE WITH IT. THERE WAS DECISIONS I MADE I MAY MAKE DIFFERENTLY NOWADAYS BUT YOU CAN'T LOOK IN THE REARVIEW MIR. YOU HAVE TO SAY I MADE THAT DECISION AND AT SOME POINT YOU HAVE TO MOVE ON. IN CLL YOU ALMOST ALWAYS HAVE TIME TO MAKE THESE DECISIONS. YOU DON'T HAVE TO RUSH THROUGH THEM. YOU WEIGH WHAT'S IMPORTANT TO YOU AND KNOW YOURSELF AND OTHERS AND I WENT FOR MY THERAPY AND I HAVE SEEN OF THE TWO TOP CLL EXPERTS IN THE WORLD AND PEOPLE WHO FOLLOW ME WHO THEY ARE AND I GOT OPPOSING RECOMMENDATION. I'M A PHYSICIAN AND A CLL EXPERT AND IT WAS TOUGH FOR ME. IT'S VERY TOUCH. MAKE A DECISION AND PUT EVERYTHING TOGETHER AND YOU MOVE FORWARD AND YOU TRY NOT TO LOOK BACK. >> I WANT TO ECHO WHAT DR. KOFFMAN SAID YOU HAVE TO LOOK AT THE DISEASE FACTOR AND THE INDIVIDUAL AND HOW'S THE PATIENT pLOOK OR IS THE PATIENT LOOKING MEDICALLY FIT? DOES THE PATIENT HAVE A LOT OF COMORBIDITIES AND IS THE KIDNEY FUNCTION OKAY. THE THIRD FACTOR IS ABOUT TREATMENT. IS THE TREATMENT THE PATIENT IS LOOK AT GOOD ENOUGH? IS THERE ANY OTHER CLINICAL TRIALS AND HOW DO THEY COMPARE TO EACH OTHER. THERE ARE THREE MOVING PARTS IF I CAN MAKE IT SIMPLER FOR YOUR DECISION. >> I WOULD ECHO, IF YOU HAVE AN OPTION TO BE WITH AN EXPERT, DO THAT, IF YOU HAVE AN OPTION TO BE IN A CLINICAL TRIAL, THERE'S NOT ONLY A SURVIVAL ADVANTAGE TO AN EXPERT BUT ALSO TO BEING IN CLINICAL TRIALS. >> I WANTED TO KNOW ABOUT THE STAGES IN ORDER. DO SYMPTOMS EVER ARISE NOT IN THAT ORDER? >> WHATEVER RISK SYSTEM YOU HOLD PUTS YOU IN A STAGE TO DETERMINE ABOUT WHAT STAGE YOU'RE AT. FOR EXAMPLE, WHAT I MEAN IS IF YOU DON'T HAVE AN ENLARGED SPLEEN BUT HAVE YOU LOW PLATELETS IT PUTS YOU AT STAGE 4. WHATEVER IS THE WORSE THING WOULD PUT YOU AT THE HIGHER STAGE. WE'RE SEEING WITH THE BLOOD CELL COUNT CAN GO DOWN OR LYMPH NODES CAN SHRINK. I WANT TO STRESS THAT'S THE MINORITY FOR MOST PATIENTS, CLL PROGRESSES OVER TIME BUT THE PACE VARIES BASED ON GENETIC AND OTHER DISEASE RISK FACTORS. >> IF I CAN ADD THERE'S NO NUMBER OF LYMPHOCYTES THAT SAYS YOU NEED TREATMENT. CAN HAVE 200,000, 500,000. IF YOU DON'T HAVE OTHER SYMPTOMS IT DOESN'T MEAN YOU NEED TREATMENT. YOU CAN WEIGHT YEARS UNTIL YOU NEED TREATMENT BECAUSE HAVE YOU A LITTLE BIT OF CLL DOESN'T MEAN YOU NEED TREATMENT. YOU'VE GONE FROM SOMEWHERE WHERE I WAS SYMPTOMATIC AND ANEMIC AND HAVING NIGHT SWEATS AND NOW YOU'RE NOT HAVING TREATMENT AND IT'S THE SAME TREATMENT CRITERIA AGAIN. IT'S JUST, OKAY, NOW I'M GETTING ANEMIC OR TERRIBLY FATIGUED. NOW IT'S TIME TO TREAT IT AGAIN. THAT HAPPENS AND THE DISEASE GETS KNOCKED BACK. >> I WANT TO THANK BRIAN AND I'VE FOLLOWED HIS PATH AND THE PILLS WHICH BECAME IBRUTINIB AND I'VE HAD A CHANCE TO TALK WITH BRIAN AND A WANT TO THANK YOU FOR EVERYTHING YOU ALL DO BECAUSE IF IT WASN'T FOR WHAT YOU DO, I WOULDN'T BE HERE SO THANK YOU. >> LET'S TAKE A BREAK AND TRY TO GET BACK DR. REISNER. >> IT'S A GREAT IDEA TO HAVE THE BIRTHDAY CAKE FOR THE STUDY THAT STARTED IN 2008. I'M HAPPY WE HAVE MANY HERE WHO AT ONE POINT ARE STILL PARTICIPATING ON THAT STUDY SO WHAT A GREAT OPPORTUNITY TO SHARE THAT CAKE TOGETHER. AND THANKS FOR THE PEOPLE WHO HAVE TALKED ABOUT BRINGING IT. WONDERFUL. THANK YOU. WE'LL LEARN ABOUT PATIENT SUPPORT GROUPS IN THE AREA. I'LL ALSO START WITH THE SHOW OF HANDS. COULD YOU RAISE YOUR HAND -- THERE IS ONE CLL SOCIETY SUPPORT GROUP FOR THE WHOLE REGION FROM PHILADELPHIA DOWN SO ONE IN PHILADELPHIA BUT SOUTH OF PHILADELPHIA AND I THINK NORTH OF NORTH CAROLINA, WE ARE IT. SO IF YOU'RE IN THE GROUP, IF YOU COULD RAISE YOUR HANDS BECAUSE I WANT TO ALLOW PEOPLE NOT IN A GROUP AFTER THE MEETING ASK ANY ONE OF US WHAT BEING A SUPPORT GROUP IS LIKE. THANK YOU ALL FOR YOUR HANDS. USUALLY THIS SLIDE GETS MORE LAUGHS BUT I LOOK MORE AT HIS EYES THAN ARM. FOR PATIENTS IT'S ABOUT WHAT LIFE FEELS LIKE WHEN YOU GET DIAGNOSED BUT I ALSO THINK THE TERM BRIAN USED OF A DEER UP HEADLIGHTS EXPRESSES VERY WELL WHAT ME AND MY HUSBAND, I'M THE CAREGIVER, EXPERIENCED WHEN WE HIS DIAGNOSED IN 2011. ALL THE QUESTIONS AND FLURRY BRIAN WAS TALKING ABOUT BEFORE OF DIGESTING THE DIAGNOSIS AND THEN FIGURING OUT WHAT YOU'RE GOING TO DO WITH THAT INFORMATION. I DON'T KNOW FINDING A SUPPORT GROUP IS THE FIRST, SECOND OR THIRD THING YOU DO BUT I HOPE THAT FOR THOSE WHO DO CHOOSE TO DO IT, THAT YOU'LL FIND IT TO BE HELPFUL AND A REWARDING EXPERIENCE BOTH IN TERMS OF THE INFORMATION YOU GET AS WELL AS THE EMOTIONAL SUPPORT YOU GET FROM THE PEOPLE INVOLVED. >> I COULD USE HELP WITH FIGURING OUT. THANK YOU. >> WELCOME TO THE CLUB NO ONE WANTED TO JOIN. YOU PROBABLY HAVE MANY WORRIES AND QUESTIONS ABOUT YOUR DIAGNOSE. >> YOU'RE NOT ALONE. THE CLL SOCIETY IS HERE TO HELP. BEFORE DISCUSSING DISEASE MANAGEMENT, LET'S REMEMBER FOUR THINGS THAT ALWAYS COME WITH OUR DIAGNOSIS BESIDES ALL THE WORRY. >> FIRST WORD IS TIME. CLL RARELY REQUIRES IMMEDIATE TREATMENT. >> YOU ALMOST ALWAYS HAVE TIME TO GET SMART ABOUT YOUR DISEASE. >> OR FIND SOMEONE WHOS. >> TWO, HEALTH AND INFORMATION. WE WILL SHARE THE HONEST FACTS FROM THE BASIC TO THE LATEST RESEARCH AND IMPORTANT CLINICAL TRIALS. >> THREE, CHANGES IN CLL MANAGEMENT. >> THE VERY BEST CHOICE TODAY IS LIKELY TO BE UPSTAGED BY MORE PROMISING OPTIONS TOMORROW. >> FOUR, CHANGES IN OURSELVES. CANCER SAY HUGE CHALLENGE BUT SOME THINGS CAN GET BETTER AFTER DIAGNOSIS. >> YOUR PRIORITY SHIFT. OUR LIVES CAN BECOME MORE FULL OF GRATITUDE AND PURPOSE. WE MAY NEVER HAVE WANTED TO JOIN THIS CLUB BUT IT COULD BE A SAFE AND NURTURING PLACE. >> STAY IN TOUCH. >> STAY STRONG. >> WE'RE YOU WILL ALL IN THIS TOGETHER. >> I LIKE THAT SLIDE BOTH FOR THE THINGS THAT IT SAYS. I THINK IT REALLY HITS SOME OF THE HIGH POINTS AND ALSO BECAUSE BEING PART OF A SUPPORT GROUP I ACTUALLY KNOW A LOT OF THE PEOPLE IN THAT SLIDE AND YOU KNOW SOME OF THEM TOO BECAUSE IT DOES START TO FEEL A LITTLE BIT LIKE A FAMILY THE WAY WE SUPPORT ONE ANOTHER. I'M GOING TO GIVE YOU A MOMENT TO PER USE THE SLIDES AS THEY COME UP -- PERUSE THE SLIDES AS THEY COME UP AND I'LL TALK ABOUT THINGS NOT ON THE SLIDE ON WHY WE DO THINGS AND WHY IT'S HELPFUL. THIS IS A LITTLE BIT ABOUT CLL SOCIETY AND WHAT THEIR MISSION. ONE OF THE THINGS THAT IS A KEY POINT IS THERE ARE LOTS OF GREAT ORGANIZATIONS THAT SUPPORT PATIENTS WITH CANCER. FROM THE RESEARCHERS THAT ARE HERE AND WE ARE LUCKY TO BE MEETING WING, TO THE CANCER SOCIETY TO THE LYMPHOMA AND LEUKEMIA SOCIETY AND THE LYMPHOMA RESEARCH FOUNDATION. EACH ARE THE LARGER GROUPS. AS YOU HONE IN AND YOU HEAR ABOUT ALL THE NEW TREATMENTS THAT ARE COMING OUT, THEY EFFECT EACH TYPE OF BLOOD CANCER DIFFERENTLY. SO WHAT WE ARE IS THAT VERY TIP OF THE ARROW. IF YOU HAVE CLL, WE ARE A GROUP THAT ALSO HAD THE SAME DIAGNOSIS THAT YOU HAVE AND CAN TALK BACK AND FORTH IN A MORE INTIMATE SUPPORT BACKGROUND ON WHAT IT MEANS FROM A PATIENT PERSPECTIVE AND THIS IS CREATED FOR THE PATIENT AND IS PATIENT-LED. I MENTIONED SUPPORT GROUPS PROVIDE TWO AREAS OF SUPPORT. ONE IS AN INFORMATION EXCHANGE AND THE OTHER IS ABOUT THE EMOTIONAL SUPPORT. WE DID A SURVEY THIS YEAR BOTH BRIAN AND THE HEADQUARTERS AND ONE IN OUR LOCAL DD.C.GROUP AND DO YOU COME HERE FOR SUPPORT OR ANOTHER REASON. WIZ HEARTENED TO -- WAS HEARTENED TO SEE THOSE WHAT CHOSE A WRITE-IN ANSWER IN ADDITION TO THE OTHER TWO AND WANTED TO SAY THEY DIT BECAUSE THEY WANTED TO -- DID IT TO HELP OTHERS AS WELL. IT'S IN PART THE FEELING YOU GET WHEN YOU KNOW YOU'RE NOT ALONE AND FROM BEING ABLE TO SHARE WHAT YOU LEARNED ALONG THIS JOURNEY WITH OTHERS. DR. REISNER TOLD US NOT TO GET PERSONAL SO I WON'T ANSWER THE QUESTION WHETHER YOUR SEX LIFE pSUPPORT GROUP BUT I HOPE YOU FIND THESE STATEMENTS TO BE TRUE BEING PART OF A COMMUNITY THAT SUPPORTS ONE ANOTHER GOING THROUGH A JOURNEY TOGETHER. IT'S ALSO ON THE INTERNET SO IT MUST BE TRUE. OUR GROUP MEETS ON THE THIRD SATURDAY OF EACH MONTH AND WE'RE NOT MEETING IN APRIL BECAUSE WE'RE MEETING HERE TODAY. OUR SUPPORT GROUP IS ABOUT -- OUR LOCAL ONE IS ABOUT 40 MEMBERS ON A LIST SERVE. AND I'D SAY A LITTLE LESS THAN HALF OF THAT NUMBER SHOW UP EACH MARATHON. AND THERE'S SOME INCONSISTENCY ON WHO FOLKS UP AND SOME FOLKS THAT COME AND GO A LITTLE MORE ERRATICALLY AND NEWBIES. AND THERE'LL BE A SLIDE A LITTLE BIT LATER ABOUT HOW SUPPORT GROUPS ARE RUN AND WE'LL TALK ABOUT HOW WE RUN OURS TOO. AND THIS IS WHAT YOU GETTING PART OF THE SUPPORT GROUP. BRIAN CREATES THIS CLL BROOD LINE NEWSLETTER WE READ AND ALL 33 GROUPS AROUND THE COUNTRY AROUND THE MONTHLY MEETINGS. AS YOU HEARD THERE'S AMAZING ADVANCES THAT HAVE BEEN HAPPENING. IBRUTINIB IS A FEW YEARS OLD AND THERE'S A WHOLE ALPHABET SOUP OF TREATMENTS AND PROMISING NEW THERAPIES OUT THERE SO BLOOD LINE SAY GREAT WAY TO KEEP APPRISED OF THAT. AND WE ALSO SEND OUT PROBABLY ONCE TO TWICE A WEEK I'LL BE FORWARDING INFORMATION ABOUT OTHER CLL SPECIFIC SUPPORT RESOURCES THAT LLS, LRF, PATIENT POWER AND OTHER GROUPS ARE PROVIDING. SO THE PEOPLE WHO ARE ON OUR SUPPORT GROUP LIST SERVE KNOW ABOUT LOCAL OPPORTUNITIES AND ALSO BOTH FROM THE E-MAILS WE SEND OUT AND LISTED ON THE CLL SOCIETY WEBSITE IS UPCOMING EVENT AND ACTIVITIES AROUND THE NATION. SOME COULD BE HELPFUL BECAUSE IT COULD BE FREQUENTLY 60 TO 90-MINUTE CONFERENCE CALLS YOU CAN DIAL IN AND HEAR FROM EXPERTS SPECIFICALLY ABOUT CLL. YES, THEY REALLY DO GET TO A GOOD NUMBER OF QUESTIONS. SO IF YOU HAVE ONE. AND THANK YOU, THEY DO SUBSIDIZE HEALTHY SNACKS. OURS TEND TO BE GRILLED VEGETABLES. SO THE OTHER POINT I WANTED TO MAKE SI MENTIONED THAT WE ARE THE ONE GAME IN TOWN FOR CLL SOCIETY. IT'S AMAZING IT'S GROWN SINCE 2015 TO HAVE 33 DIFFERENT CHAPTERS AROUND THE COUNTRY. THAT IS TREMENDOUS GROWTH BUT WE GET PEOPLE WHO CALL FROM BALTIMORE AND SAY ARE YOU REALLY THE CLOSEST THING TO ME AND I GUESS IT DEPENDS WHERE THEY WANT TO DRIVE TO PHILADELPHIA OR NOT. WE DO HAVE MEMBERS IN FROM FREDRICKSBURG EVERY MONTH OR THE EASTERN SHORE OF MARYLAND. SO IF YOU LIVE IN ONE OF THOSE OUTLYING AREAS AND I'M SURE YOU'RE FINDING TODAY WORTH YOUR WHILE, BUT YOU MAY FIND IT MORE CHALLENGING TO COME ONCE A MONTH WHERE WE'RE IN VIENNA, VIRGINIA. THE CLL SOCIETY PROVIDES GOOD TRAINING FOR FACILITATORS IF YOU'RE THINK YOU MIGHT BE INTERESTED IN SETTING UP YOUR OWN GROUP BETWEEN NORTH CAROLINA AND PHILADELPHIA. I'D BE HAPPY TO TALK TO YOU ABOUT THAT AFTER THE PROGRAM AS WELL. SO SOME OF THIS RULES OF THE ROAD IN OUR SUPPORT GROUP IS WHAT WE DISCUSS, WE DISCUSS PRIVATELY. WE'RE ALL PATIENTS SO WE DO NOT PROVIDE MEDICAL ADVICE. ON OUR SIR HAVE A -- SURVEY WE DECIDED THREE TIMES A YEAR WE WANT EXPERTS OR SURVIVORSHIP EXPERTS THAT TALK ABOUT HOW TO STAY HEALTHY WHEN YOU'RE JUST BEYOND THE DIRECT TREATMENT OPTIONS AND WE ALSO TALKED ABOUT WHETHER WE MIGHT WANT TO DO A DISCUSSION ABOUT FINANCIAL MATTERS. WE SOMETIMES MIX IT UP IN TERMS OF WHAT WE'RE DEGREE -- DOING. IN TERMS OF NO DUMB QUESTIONS WE HAVE 15 TO 20 PEOPLE AROUND THE TABLE. WE PAY ATTENTION TO THE NEW FOLKS JOINING US AND I'LL TRY TO MAKE CONTACT FROM THE FRONT OF THE ROOM SO IF I GET A QUIZZICAL LOOK ABOUT THE RYE PROGRESSION OR TALK ABOUT IBRUTINIB OR THEIR FISH RESULTS OR IBIG WE'LL STOP AT DIFFERENT POINTS TO JUST DO A CHECK IN AND SAY DO YOU UNDERSTAND THE VOCABULARY WE'RE USING AND WE'LL SORT OF SIDE TRACK A LITTLE BIT SO WE KNOW AS WE'RE TALKING EVERYONE IN THE ROOM IS UNDERSTANDING WHAT'S BEING SAID. THAT INTERRUPTING THING, DON'T TELL BRIAN, BUT WE DO A LITTLE. WE DO HAVE DIFFERENCES OF OPINIONS BUT WE'RE ALSO RESPECTFUL IN HOW WE DISCUSS THAT. THERE'S NOT DEBATES GOING ON ABOUT PUT TOGETHER A LOCAL RESOURCE GUIDE OF THINGS WE HEARD OUR DOCTORS TELL US ABOUT GETTING VACCINES EARLIER IN YOUR TREATMENT. WHAT YOUR MOM TOLD YOU ABOUT BEING SUNSCREEN BEING MORE IMPORTANT IF YOU'RE FACING CANCER AND SPECIFICALLY CLL DIAGNOSES. WE TRY TO SHARE THOSE TIPS WHEN FOLKS ARE COMING IN AND HAVE WRITTEN THAT UP AS WELL. I DON'T HAVE TO COME TO EVERY MEETING. NO, YOU DON'T HAVE TO SHARE BUT WE HASN'T FOUND ANYONE YET WHO HASN'T WANTED TO AT SOME POINT TALK ABOUT WHAT'S GOING ON WITH THEM. WE LET THE NEW FOLKS TALK ABOUT THEIR QUESTIONS AND WE TRY TO GO AROUND THE ROOM A SECOND TIME AND ASK PEOPLE WHO HAVE NEW UPDATES IN WHAT'S HAPPENED WITH THEM IN THE PAST MONTH TO SHARE THE INFORMATION SO THE GROUP CAN DISCUSS AND GIVE SUPPORT AND FEEDBACK AS WELL. OUR MEETINGS GO FROM 3:00 TO 5:00 AND WE START PROMPTLY AND END PROMPTLY AND HAVE A BATHROOM BREAK. THE CLL SOCIETY WEBSITE PAGE CAN DIRECT YOU TO WHEN OUR MONTHLY MEETINGS ARE. WE SOMETIMES TAKE AUGUST OFF SO YOU'LL SEE IF THERE'S ANY SORT OF CANCELLATION AND WE TOOK DECEMBER OFF BECAUSE OF VACATIONS AND AS IS TRUE WITH THE LAST MINUTE OR SO I HAVE LEFT AND WITH THE TRADITION AND CULTURE I HAVE, I WILL ALLOW FOR INTERRUPTIONS SO YOU CAN TELL ME IF I MISSED ANYTHING IMPORTANT. OUR CO-CHAIRS, IS THERE ANYTHING YOU'D WANT TO ADD? >> THANK YOU FOR ALLOWING US THE TIME AND THANK YOU FOR HOSTING THIS EVENT. >> GOOD AFTERNOON. I'M ONE OF THE FELLOWS WORK IN DR. REISNER'S GROUP WITH THE CLL GROUP AND WORKING ON THE VACCINE FILES. THANK YOU FOR COMING TODAY AND CARVING TIME OUT OF YOUR AFTERNOON. PATIEN PATIENTS, MY FRIENDS OFTEN ASK ME WHETHER IT'S EXHAUSTING OR DIFFICULT TAKING CARE OF CANCER PATIENTS EVERY DAY. I CAN SAY IT COULDN'T BE FURTHER FROM THE TRUTH. I FEEL SO HONORED BEING ABLE TO TAKE CARE OF CANCER PATIENTS AND EVERY PATIENT IS SUCH AN INSPIRING STORY AND YOU'RE THE REASON WHY WE ALL COME TO WORK EVERY DAY AND TO KEEP US GOING AND I WANT TO MAKE SURE YOU ARE GIVING JUST AS MUCH TO US AS PHYSICIANS AS MUCH AS WE'RE PROVIDING CARE FOR YOU AS WELL. OVER THE NEXT COUPLE MINUTES WE'LL BE TALKING ABOUT EASY STEPS YOU CAN DO IN REDUCING YOUR RISK OF INFECTION WHETHER YOU HAVE CLL OR NOT. VACCINATIONS ARE ONE OF THE BIG SUCCESS STORIES OF MEDICINES. MANY OF THE INTERVENTIONS WE RECOMMEND ON A DAY TO DAY BASIS PALE IN COMPARING WITH THE EFFECT OF VACCINES. THE CENTERS OF DISEASE CONTROL ESTIMATES AROUND 720,000 LIVES HAVE BEEN SAVED IN THE PAST 20 YEARS LONE IN THE U.S. -- ALONE IN THE U.S. ALONE. THAT'S MORE PEOPLE THAN LIVE IN THE ENTIRE DISTRICT OF COLOMBIA. IT REMAINS ONE OF THE MOST EFFECTIVE AND CHEAPEST WAYS IN HOW PATIENTS CAN REDUCE THEIR RISK OF GETTING INFECTIONS. IN PARTICULAR FOR CLL PATIENTS, INFECTIONS ARE A BIG PROBLEM. AND IN FACT, MANY PATIENTS WITH CLL DON'T NECESSARILY DIE WITH CLL ITSELF BUT FROM CONSEQUENCES OR FROM INFECTIONS THEMSELVES. WE'RE TRYING TO FIND WAYS HOW TO REDUCE THE RISK OF INFECTIONS AND VACCINATIONS IS A WAY TO DO THAT. SURPRISINGLY WE KNOW VERY LITTLE HOW WELL VACCINES WORK IN CLL PATIENTS SPECIFICALLY. TO DATE THERE'S BEEN SMALL STUDIES SHA THAT HAVE BEEN PERFORMED PREDOMINANTLY FOR THE INFLUENCE OF VACCINE AND THERE'S SMALL STOUDIES OF ABOUT 20 PATIENTS WITH VARYING RESPONSE ABOUT 20% SO THERE'S BAGE -- A BIG NEED FOR INFORMATION. WHAT'S ARE THE RECOMMENDATIONS FOR PATIENTS TO RECEIVE VACCINES. YOU CAN SEE THOSE CONSIDERED SAFE AND REASONABLE FOR CLL PATIENT TO GET. THESE ON PATIENTS WITH IMMUNO COMPROMISING CONDITIONS AND WE KNOW WHETHER THEY'RE TREATED OR UNTREATED THEY HAVE A HIGH RISK OF RECURRING INFECTIONS. WHAT THE CDC PUTS OUT INCLUDES PATIENTS WITH CLL AND HIV AND CHRONIC MEDICAL CONDITIONS AND OTHER HEMATOLOGIC CONDITIONS. YOU SEE ROUTINE NON-LIVE VACCINES. THESE ARE VACCINATIONS ANYONE SHOULD GET, INFLUENZA, SHING ALS, HEPATITIS B AND TETANUS AND YOU SEE THOSE FOR TRAVEL. THAT DEPEND IT'S YOU'RE LEAVING THE COUNTRY AND GOING TO CERTAIN AREAS OF THE WORLD AND HOW MUCH TIME YOU'RE SPENDING THERE AND WHAT ARE YOUR EXPECTED ACTIVITIES. WHENEVER YOU PLAN A TRIP ABROAD WE RECOMMEND SPEAKING WITH YOUR PRIMARY CARE DOCTOR OR EVEN BETTER A TRAVEL MEDICINE DOCTOR TO ADVISE YOU ON WHICH OF THESE VACCINES IS APPROPRIATE. ONE THING I WANT YOU TO REMEMBER AND TAKE HOME IS LIVE VACCINES ARE NOT RECOMMENDED FOR PATIENTS WITH CLL. LIVE VACCINES USE ESSENTIALLY THE WHOLE VIRUS AND THEY JUST MAKE IT LESS LIKELY THE VIRUS WILL CAUSE THE DECEASE BUT THE VACCINE WILL -- DISEASE BUT THE VACCINE WILL STILL PROVIDE SOME PROTECTION. SINCE PATIENTS WITH CLL ARE IMMUNOCOMPROMISED THERE'S A RISK. THE RISK IS THE OLD SHINGLES VACCINE AND THE MEASLES, MUMPS AND RUBELLA AND CERTAIN TRAVEL VACCINES ARE INCLUDED HERE TOO. MORE SPECIFICS ABOUT THE PNEUMONIA VACCINE. IF YOU HAVEN'T RECEIVED ANY OF THESE VACCINES BEFORE WE RECOMMEND TO GET THE PREVNAR FOLLOWED BY THEPNEUMOVAX. WILL WILL STOP OFFERING IT AT 65 AND WE GENERALLY RECOMMEND MOST PEOPLE TO GET THEM EVERY FIVE YEARS AS LONG AS THEY'RE HEALTHY. WE ALSO GET A QUESTION ON WHAT INFLUENZA VACCINE TO USE. THERE'S DIFFERENT PREPARATIONS OF THE FLU VACCINE. THERE'S ALSO A HIGH-DOSE FLU VACCINE CALLED FLUZONE. THAT PARTICULAR VACCINES THROUGH MORE TIMES MORE OF THE ANTIGEN AND CREATES MORE IMMUNE RESPONSE IN PATIENTS. THERE'S A BIG TRIAL INCLUDING 30,000 PATIENTS THEY HAVE THE HIGH DOSE AND STANDARD DOSE. THERE'S NOT MUCH OF A DIFFERENCE IN TERMS OF HOW MUCH PATIENTS DEVELOP THE FLU. THERE'S 1.4% OR 228 OUT OF 15,000 VERSUS 300 OUT OF 15,000. SO IT DID LOOK LIKE MORE EFFECTIVE BUT YOU CAN SEE WHEN YOU LOOK AT THE NUMBERS, THEY'RE RELATIVELY SMALL. IT CONCLUDE THE CDC DOESN'T RECOMMEND ANY FLU VACCINE OVER ANOTHER. SO GETTING ANY FLU VACCINE IS ANOTHER. IF THE HIGH-DOSE VACCINE IS AVAILABLE, THAT'S THE ONE WE RECOMMEND BECAUSE IT MAY BE SLIGHTLY BETTER AT PROTECTING YOU BUT IT SHOULDN'T STOP YOU FROM GET FLU SHOPPE -- SHOT AND IF YOU DELAY IT A MONTH THAT'S WHEN YOU COULD GET IT. IF YOU HAVE A CHOICE, GO FOR THE HIGH DOZE. -- DOSE. WITH ALL THE UNCERTAINTY AND HOW WELL PATIENTS RESPOND TO VACCINES, WE DEVELOPED TWO CLINICAL TRIALS TESTING NEW VACCINES, THE SHINGLES AND HEPATITIS B VACCINE. AND WE'RE NOT ONLY INTERESTED IN LOOKING HOW WELL IT WORKS IN CLL PATIENTS BUT ALSO FIGURING OUT THE RIGHT TIMING. IS IT GOOD TO GET THE VACCINE WHILE YOU'RE ON ACTIVE SURVEILLANCE OR IS IT BETTER WHILE YOU'RE GETTING TREATMENT SPECIFICALLY WITH IBRUTINIB OR ACALABRUTINIB. AND SHINGLES AND THE CHICKEN POX VIRUS THAT ESSENTIALLY ALL OF US HAVE BEEN INFECTED WITH AS CHILDREN AND THE VIRUS LIVES IN SIDE OF OUR BODIES HIDING WITHIN THE NERVE ROOTS. WHEN WE GET SICK OR THE OLDER MORE IMMUNO COMPROMISED WE CAN GET A PAINFUL RASH. EVEN WHEN THE RASH GOES AWAY THE PAIN CAN LINGER MANY MONTHS TO COME. ANY U.S. CITIZEN 1 OF 3 IS EXPECTED TO DEVELOP THE SHINGLES OVER THEIR LIFE TIME AND THAT INCREASES IN PATIENTS WHO ARE IMMU IMMUNOCOMPROMISED. THERE'S ONE THAT'S NEW TO GIVE TO PATIENTS WITH CLL. IT'S NOT POSSIBLE TO GET THE SINGLES FROM THE VACCINE. ONLY 29 PATIENTS COMPARED WITH 200 SO TEN TIMES FEWER PATIENTS DEVELOPED SINGLES. SO MORE THAN 90% PROTECTED. EXTREMELY PROTECTIVE. SO MUCH SO THE NEW SHINGLES VACCINE IS RECOMMENDED FOR ALL PATIENTS EVEN IF THEY RECEIVE THE PREVIOUS SINGLE VACCINE BUZ IT'S THAT MUCH BETTER. AND ONCE PEOPLE GET IT AND HAVE A CHRONIC FORM OF THIS IS INCURRABLE EXCEPT FOR WITH A LIVER TRANSPLANT AND ABOUT 850,000 PEOPLE IN THE U.S. LIVE WITH THE DISEASE SO ABOUT 1 IN 400 PEOPLE. IT'S GENERALLY TRANSMITTED THROUGH BLOOD AND TO INCREASE PUBLIC HEALTH MEASURES AND INCREASE SCREENING PRODUCTS THE IT'S DECREASED RECENTLY BUT STILL A LOT OF PEOPLE LIVE WITH THE DISEASE AND MANY PEOPLE ACQUIRE HEPATITIS B AS WELL. WHO SHOULD GET VACCINED? PEOPLE IMMUNOCOMPROMISED AND THOSE WHO WANT PROTECTION FROM HEPATITIS B. IT'S VERY EFFECTIVE AND CREATES A POSITIVE EFFECT IN MORE THAN 90% OF PATIENTS AND MORE EFFECTIVE THAN PREVIOUS VACCINES AND THE CDC RECOMMENDS MANY GET THE SHOT. SIDE EFFECTS? THESE ARE NEWER GENERATION VACCINES. SO WITH INCREASED EFFECTIVENESS AND PROTECTING PATIENTS THERE'S A DOWN SIDE OF MORE SIDE EFFECTS. THE HEPATITIS, IN TERMS OF WHEN WE LOOK AT CLINICAL TRIALS AND LOOK THET SIDE EFFECTS WE HAVE CERTAIN GRADES. GRADE 3 IS A MAJOR THRESHOLD BECAUSE THEY USUALLY REQUIRE A MEDICAL INVENTION. ONLY 1 IN 20 PATIENTS NEEDED A MEDICAL INTERVENTION. OTHER THAN THAT THE SIDE EFFECTS ARE SIMILAR TO OTHER VACCINES. THERE'S LOCAL REACTIONS IN PAIN, REDNESS, SWELLING AT THE SITE. SOMETIMES PEOPLE CAN ALSO GET FLU-LIKE SYMPTOMS. THE WAY HOW VACCINES WORK, THEY TRY TO INDUCE THE IMMUNE SYSTEM SO IT RAMPS UP THE IMMUNE SYSTEM AND CAUSES A FLU-LIKE SYMPTOM WITHOUT CAUSING THE FLU AND IT CAN LEAD TO HEADACHES, MUSCLE MAKES AND FEVERS. IT'S MORE EFFECTIVE THAN OTHER VACCINES. SOME DEVELOP SYMPTOMS AND THEY'RE GENERALLY MILD AND GENERALLY GO AWAY WITHIN TWO DAYS. WE VACCINE ABOUT 55 PATIENTS SO FAR AND WE HAVEN'T HEARD ANY MAJOR SIDE EFFECTS FROM THIS VACCINE AND WE ASKED PATIENT TO CALL WITH SIDE EFFECTS AND WE HAVEN'T RECEIVED ANYTHING HUGELY CONCERNING FROM OUR PATIENTS. IN SUMMARY? WE'RE TRYING TO CHARACTERIZE HOW WELL THIS WORKS IN ORDER TO GUIDE PHYSICIANS AND PATIENTS IN THEIR CHOICE IN VACCINES AND WE'RE TRYING TO LEARN THE TIMING. SIT BETTER TO TREAT PATIENTS BEFORE STARTING TREATMENT OR AFTER TREATMENT? THE DESIGN IS PRETTY SIMPLE. THE TRIAL FOR THE VACCINES THEMSELVES ONLY LAST SIX MONTHS. YOU'RE SEEN IN CLINIC. YOU GET A REGULAR DOCTORS VISIT AND BLOOD DRAW. THEN YOU GET THE FIRST SHOT OF THE SHINGLES OR HEPATITIS OR BOTH AND AFTER THREE MONTHS THE SAME THING, YOU GET THE SECOND SHOT AND IN SIX MONTHS IS JUST THE BLOOD DRAW. THAT'S WHEN WE LOOK AT THE IMMUNE RESPONSE AND IF YOU'RE BODY'S DEVELOPED PROTECTIVE TIDEERS. WHO CAN PARTICIPATE? PATIENTS UNTREATED FOR THEIR CLL OR PATIENTS THAT ARE CURRENTLY RECEIVING IBRUTINIB OR CAL ABRUTE ANYBODY. NOT -- OR ACALABRUTINIB. WE CAN'T INCLUDE PATIENT WHO'S ARE IVIG AND NO OTHER IMMUNOSUPPRESSING STEROIDS. NO ACTIVE SHINGLES INFECTION OR HISTORY OF SHINGLES INFECTION IN THE LAST YEAR AND FOR HEPATITIS WE ASK FOR PATIENTS NOT TO RECEIVE THE VACCINE BEFORE. >> I WANTED TO THANK THE CLL SOCIETY AND TEAM TO THANK THE LYMPHOMA SOCIETY TO BE HERE. PROUD TO BE HERE TO REPRESENT OUR ORGANIZATION. AND I'LL JUST SHARE A LITTLE BIT ABOUT OUR PATIENT ACTIVITIES PRIMARILY AND WHAT WE DO AND UPCOMING THINGS AND CLL SPECIFIC RESOURCES. SO AS MANY OF YOU LIKELY KNOW, OUR MISSION IS TO CURE LEUKEMIA, LYMPHOMA AND MYELOMA AND IMPROVE THE QUALITY OF LIFE FOR PATIENTS AND THEIR FAMILIES. WE'RE THE VOICE FOR ALL BLOOD CANCER PATIENTS AND LOOK TO ENSURE TREATMENTS FOR ALL BLOOD CANCER PATIENTS AS WELL AS. ONE OF OUR BIG PRIORITY IS RESEARCH. WE FUNDED OVER 1.3 MILLION IN BLOOD CANCER RESEARCH SINCE OUR INCEPTION IN 1949. WE'RE PROUD OF THAT AND WE'VE ALSO HAD OUR HAND IN 19 OF 21 NEW BLOOD CANCER DRUGS THAT HAVE BEEN APPROVED BY THE FDA LAST YEAR SO AGAIN VERY PROUD OF OUR RESEARCH EFFORTS BUT WITH ALL THESE NEW TREATMENT ADVANCES THEY DON'T MATTER MUCH IF WE CAN'T HAVE PATIENTS ACCESSING NEW TREATMENT. WE FOCUSSED ON ADVOCACY EFFORTS TO INCREASE ACCESS TO THE NEW TREATMENTS. AND THINGS LIKE ORAL PARITY AND OUR ADVOCACY EFFORTS ARE STRONG AS WELL. AND THE PART OF MISSION I WORK MOST CLOSELY IN IS PATIENT ACCESS OR SERVICES AND I'LL GO INTO MORE DETAIL. WE'RE HERE FOR BLOOD CANCER PATIENTS AND CAREGIVERS THROUGH THEIR JOURNEY. WE'RE HERE TO SUPPORT YOU AND HERE TO HELP. WE HAD ACTUALLY SEVERAL DIFFERENT AREAS OF THE SOCIETY WORKING ON PATIENT ACCESS. WE HAVE OUR INFORMATION SPECIALISTS. I'LL BE TALKING ABOUT OUR EXPERTS IN THE COUNTRY TO HELP EXPERTS EARLY IN THEIR DIAGNOSIS AND SUPPORT. WE HAVE OUR CLINICAL TRIAL SUPPORT CENTER I'LL BE TALKING MORE ABOUT WHICH IS EXCITING AND RELATIVELY NEW. WE HAVE OUR NATIONAL PATIENT AND PROFESSIONAL EDUCATION TEAM IN NEW YORK WHERE WE'RE BASED NATIONALLY AND WE HAVE VOLUNTEERS HELP US TO IMPLEMENT OUR PATIENT ACCESS GOALS WHICH IS ULTIMATELY CONNECTING MORE PATIENTS TO US AFTER DIAGNOSIS. YOU WANT TO REACH EVERY PATIENT AND CAREGIVER AND THEN PROVIDE EDUCATION AND SUPPORT AND ACCESS AND DO A LOT OF PROVIDER BUILDING AND OUTREACH TO HEALTH CARE PROVIDERS AND TO INCREASE REFERRALS OF PATIENTS AN CAREGIVERS TO US. OUR INFORMATION RESOURCE CENTER IS A GROUP OF 13 MASTER'S PREPARED WORKERS AND NURSE AN EDUCATORS AT THE FRONTLINE ANSWERING PATIENT AND CAREGIVER QUESTIONS. THEY RESPOND TO OVER 1500 INQUIRIES A MONTH. LAST YEAR SERVED OVER 13,000 HOUSEHOLDS. THEY DO A GREAT JOB AND THEN LOCALLY WE FOLLOW-UP AND YOU'LL HEAR MORE ABOUT THAT BUT THEY'RE THE FIRST STOP IN A JOURNEY WHEN SOMEONE'S DIAGNOSED WITH BLOOD CANCER. THEN WE ALSO HAVE OUR CLINICAL TRIALS SUPPORT CENTER CONSISTS OF FIVE SPECIALLY TRAINED NURSE NAVIGATORS. WE'VE HAD GREAT SUCCESS IN HELPING PATIENTS GET ENROLLED IN TRIALS. SINCE OUR INCEPTION WITH THE PROGRAM WE HELPED 562 PATIENTS FIND A TRIAL AND CLOSE TO 60% OF THOSE MEDICALLY ELIGIBLE HAVE BEEN ENROLLED. THAT'S A GREAT RESPONSE. WE ARE PROUD OF THAT AND HAD OVER 6,000 INTERACTIONS AND MOST OF THE TIMES THEY TALKED TO PATIENTS AND CAREGIVERS AND A NUMBER OF INTERACTIONS TO GET SOMEONE ENROLLED IN A TRIAL WAS ABOUT 14 ON AVERAGE. HOW THIS WORKS IS SOMEONE WANTS TO GET IN TOUCH WITH A CLINICAL TRIAL CENTER AND THEY REACH OUT TO THE CENTER AND QUESTIONS AND INTERESTS ABOUT CLINICAL TRIALS COMES UP AND OUR INFORMATIONISTS ARE TRAINED AND CAN HELP IN BASIC CLINICAL TRIALS SEARCH AND NAVIGATING BUT IF IT'S MORE COMPLICATED THEY WOULD THEN PULL IN OUR CLINICAL TRIAL CENTER STAFF. WE TALKED ABOUT CLINICAL TRIALS TODAY AND WE'RE PROUD OF THIS NEW ARM THAT'S DOING GREAT WORK. THIS TALK I WON'T GET INTO GREAT DETAIL SINCE I'M THE LAST SPEAKER I'LL RUN THROUGH MY SLIDES. THIS GIVES A SNAPSHOT OF HOW MANY PEOPLE WE EDUCATED AND WE GIVE OUT A LOT OF INFORMATION. WE ALSO HAVE NUTRITION CONSULTATIONS NOW AS WELL AND LAST YEAR ABOUT 1,000 PATIENTS AND CAREGIVERS AND WE HAVE A PODCAST SERIES THAT'S RELATIVELY NEW AND MANY PEOPLE ARE CHECKING THAT OUT AND THIS YEAR WE'RE DOING EVEN MORE WITH CLINICAL TRIALS AND SURVIVORSHIP AND PEDIATRIC WORK. THIS IS JUST A SNAPSHOT OF OUR DISEASE AND EDUCATIONAL MATERIALS. WE HAVE TWO SPECIFIC THINGS ON CLL. THERE'S A DETAILED DISEASE BOOKLET AND ONE THAT'S MORE OF A GUIDE FOR PATIENTS AND CAREGIVERS. WE HAVE THE LEADING SOURCE OF OVERALL BLOOD CANCER INFORMATION, EDUCATION AND SUPPORT. AND THE COMMUNITY IS ALSO RELATIVELY NEW. IT'S A NEW SOCIAL ENGAGEMENT SITE TO REGISTER AND STAY CONNECTED AND THERE'S WONDERFUL DISCUSSION GROUPS FOR CLL AND CAREGIVERS AND WE HAVE INFORMATION ON CLINICAL TRIALS AND POST QUESTIONS OF THE DAY AND WE POST INFORMATION AND IT HELPS IMPROVE THE WORK WE'RE DOING. I ENCOURAGE YOU TO CHECK IT OUT. THERE'S A LINK ON OUR WEBSITE AND PROFESSIONALS CAN JOIN AND OUR STAFF CERTAINLY OUR MEMBERS AND WE HAVE OUR INFORMATION SOURCE MONITOR FOR DIFFERENT COMMENTS AND THINGS AND IF SOMEONE IS REACHING OUGHT THROUGH THAT MEANS AND NEEDING SUPPORT THEY DO ADDITIONAL FOLLOW-UP. I JUST WANT TO MENTION IT'S A GREAT NEW SOCIAL ENGAGEMENT SITE WE HAVE. FINANCIAL ASSISTANCE. WE TALKED ABOUT THE COST OF THE NEW MEDICATIONS AND FINANCIAL BARRIERS DO EXIST AT TIMES FOR PATIENTS. WE HAVE A NATIONAL CO-PAY ASSIST ASSISTANCE PROGRAM AND WE HAVE A CLL FUND AND I'LL TALK MORE ABOUT THAT IN THE LAST SLIDES BUT I WANTED TO MAKE SURE YOU KNEW ABOUT THAT. WE ALSO HAVE A TRAVEL ASSISTANCE PROGRAM THAT HELPS WITH TRAVEL. CERTAINLY CAN BE LOCAL, PARKING AND MILEAGE AROUND HERE IF YOU'RE LOCAL. PEOPLE THAT NEED TO TRAVEL OUT OF STATE FOR A CONSULT OR TREATMENT CAN GET HELP AS WELL. AND WE HAVE AN URGENT NEED PROGRAM. SO THINGS LIKE RENT OR GROCERIES OR UTILITIES IF SOMEONE'S IN CRISIS. WE CAN LOOK TO SUPPORT PATIENTS AND CAREGIVERS THAT WAY. THERE'S A FEW CAVEATS. IT IS OPEN FOR PEDIATRIC FAMILIES, YOUNG ADULT, PATIENTS AND FAMILIES AND FOR OUR ADULT POPULATION HAVE YOU TO BE ENROLLED IN THE CLINICAL TRIAL. THAT'S ONE OF THE ELIGIBILITY NOR PROGRAM AND THE TOP THREE PROGRAMS HAVE AN INCOME GUIDELINE OF 500% OF POVERTY LEVEL. SO MANY OF OUR MIDDLE INCOME FAMILIES ARE ABLE TO APPLY AND GET APPROVED. IT IS A VERY GENEROUS PROGRAM AND IF YOU HAVE QUESTIONS, I'LL BE HERE A FEW MINUTES AFTER BUT TO CHECK THAT OUT AND THERE'S SOME INFORMATION YOU GUYS PROBABLY PICKED UP EARLIER AS WELL AND WE LAUNCHED THE LLS PATIENT AID AND IT PROVIDES A $100 STIPEND FOR ACTIVE TREATMENT OR FOLLOW-UP CARE AND IF SOMEONE FEELS THE NEED AND WANTS TO GET THAT STIPEND PATIENTS CAN APPLY THEMSELVES OR WORK WITH A PROFESSIONAL TO HELP THEM. WE TALKED ABOUT THE NATIONAL WAYS WE CONNECT WITH PATIENTS AND CAREGIVERS. WE DO A LOT OF IN THE LOCAL COMMUNITIES AND THESE ARE SOME OF OUR CORE PROGRAMS AND SERVICE. AS A MENTIONED, OUR INFORMATION SPECIALTY WITH THE FIRST POINT OF CONTACT AND STAFF LIKE MYSELF OR TRAINED VOLUNTEERS FOLLOW-UP AND OUR TERRITORIES SHARE LOCAL RESOURCES LIKE SUPPORT GROUPS OR MAYBE AN UPCOMING PROGRAM THAT'S HAPPENING. WE ALSO HAVE LLS SUPPORT GROUPS. SOME ARE DISEASE-SPECIFIC. SOME ARE ALL BLOOD CANCERS AND CAREGIVERS. SOME ARE PEDIATRICS. WE HAVE A VARIETY OF DIFFERENT SUPPORT GROUPS AROUND THE COUNTRY AND LOCALLY. AS I MENTIONED, YOU GET A LOT OF OUTREACH AND EDUCATION WITH MEDICAL PROVIDERS. WE ALSO DO VARIOUS DISEASE, SURVIVORSHIP AND EDUCATION PROGRAMS. MY TERRITORY, I COVER MARYLAND, D.C. AND NORTHERN VIRGINIA. I'M DOING PROGRAMMING IN THOSE AREAS AND THEY'RE VIRTUALLY ON THE WEBCAST AND GO TO OUR WEBSITE AND CONNECT WITH YOUR LOCAL CHAPTER. YOU CAN ALSO SEE THE NATIONAL PROGRAMS AND WEBCASTS AND SUCH WE HAVE COMING UP. AND WE ALSO HAVE PEER-TO-PEER. I WAS TALKING TO SOME OF YOU ON THE BREAK AND I KNOW CERTAINLY WITH THE SUPPORT GROUPS PEOPLE GET PEER-TO-PEER CONTACT. THIS IS DESIGNED TO CONNECT ONE-ON-ONE WITH IT CAN BE A NEW PATIENT NEWLY DIAGNOSED OR A CAREGIVER AND WANT TO TALK TO SOMEONE ELSE AND IT'S NORMALLY DONE BY THE PHONE AND IT'S MORE OF A TELEPHONIC PROGRAM OF SUPPORT AND IT CAN BE USED AT WE HAVE A GREAT ROBUST GROUP Y. AROUND THE COUNTRY OF TRAINED VOLUNTEERS AND WE LOOKED FOR NEW VOLUNTEERS AND I WANT TO MENTION YOU'RE WELCOME TO REACH OUT IF YOU NEED THAT SERVICE AS WELL. >> CANCER CONFERENCES IS ONE OF OUR SIGNATURE EVENTS. WE'RE LUCKY TO HAVE ONE HERE I GET TO HELP I MPLEMENT. WE HAVE OUR BLOOD CANCER CONFERENCE NEXT WEEK THE 13th IS AT THE HYATT NEAR UNION STATION FROM 9:00 TO 3:00. WE HAVE A SURVIVORSHIP GURU AND WE HAVE DR. YAZEE AND OTHER BLOOD CANCER AND SURVIVORSHIP TOPICS AND RESOURCES AND FREE FREQUENT FAST AND LUNCH. I BROUGHT SOME FLYERS. I KNOW SOME TOOK THEM AND WE ARE STILL REGISTERING. WE HAVE BLOOD CANCER CONFERENCES ALL OVER THE COUNTRY SO TAKE A LOOK AND SEE IF THERE'S ONE IN YOUR COMMUNITY. THIS IS WHERE PATIENTS CAN GO TO GET INFORMATION ON OUR SUPPORT RESOURCES WE'VE BEEN TALKING ABOUT. I WANTED TO POINT THAT OUT. AND REALLY MORE CLL SPECIFIC RESOURCE AND LOCAL RESOURCES HERE. I MENTIONED WE HAVE THE CLL DISEASE BOOK IN THE GUIDE AND WE HAVE AN AWESOME CLL ONLINE CHAT WEEKLY ON WEDNESDAYS 8:00 TO 10:00 EASTERN STANDARD TIME. GO TO OUR WEBSITE AND REGISTER AND JOIN THAT. WE'D LOVE TO HAVE MORE PARTICIPANTS. WE ALSO HAVE THE CLL FUND AS OUR CO-PAY ASSISTANCE PROGRAM AND IT'S OPEN WITH THE FUNDS WE HAVE AVAILABLE AND THEY'RE POTENTIALLY ELIGIBLE FOR UP TO $8,000 OF ASSISTANCE IF THEY'RE ELIGIBLE AND APPROVED AND WE ENCOURAGE YOU TO CHECK THAT OUT. PEER-TO-PEER SUPPORT I MENTIONED. WE CAN CONNECT YOU WITH THE CLL SURVIVOR OR CAREGIVER THAT'S GONE THROUGH SIMILAR EXPERIENCES OR TREATMENTS. WE'RE HAPPY TO CONNECT YOU. YOU MENTION THE NUTRITION CONSULT AND WE DON'T HAVE A CLL SPECIFIC SUPPORT GROUP AND WE DEFINITELY SHARED THE CLL SOCIETY AND IF WE TALKED TO PEOPLE ELSEWHERE, DIRECT THEM, THEY'RE A GREAT RESOURCE. WE DO HAVE A LEUKEMIA LYMPHOMA GROUP AND HAVE A GROUP IN THE BALTIMORE AREA AND WE HAVE ONE IN HARTFORD COUNTY AND BELAIR. WE HAVE SEVERAL BLOOD CANCER GROUPS IN THE AREA PATIENTS AND CAREGIVERS CAN JOIN. WE ALSO HAVE A PODCAST. YOU CAN CHECK OUT THE ARCHIVED VERSION ON OUR WEBSITE AND DOWNLOAD THAT AND I SAW CLL RISK FACTORS AND RESEARCH. THEN WE HAVE AN UPCOMING WEBCAST IN MAY. WE HAVE PRESENTERS FOR UPDATES ON CLL. THOSE ARE SOME OF THE MORE SPECIFIC RESOURCES I WANT TO BE ABLE TO SHARE WITH YOU. AGAIN, CHECK OUT OUR WEBSITE AND GET IN TOUCH WITH OUR NATIONAL ORGANIZATION OR LOCAL CHAPTER AS WELL. AND THANK YOU AGAIN FOR ALLOWING US TO BE HERE. IT'S BEEN A PLEASURE AND CONGRATS FOR ALL OF YOU AND WE WISH YOU WELL IN OUR -- YOUR JOURNEY. THANK YOU. >> SO IT'S MY PLEASURE TO TRY TO WRAP UP IN THE SENSE OF A BRIEF SUMMARY AND CONCLUSIONS OF WHERE I THINK WE ARE. IN 2019 WE HEARD SOME THOUGHTS AND WE'LL HAVE TIME FOR QUESTION AND ANSWER. HOW DO WE ACTUALLY PICK OUR FAVORITE OR THE RIGHT ONE. SO THIS IS REALLY A LITTLE BIT OF A DILEMMA BUT IT'S A GOOD THING. THERE WERE TIMES WHERE IT WAS FCR OR NOTHING AND NOW WE HAVE GOOD CHOICES. LET ME START WITH WHAT I THINK WE KNOW IN 2019. SO FOR MOST PATIENTS, IBRUTINIB IS BETTER THAN CHEMOTHERAPY. I THINK THAT'S CLEARLY SHOWN IN VERY WELL DONE CLINICAL TRIALS. FCR AND BR DO NOT WORK IN PATIENTS WITH DELETION 17P. CONFUSING THIS SHOULD BE OVER. THERE MAY BE A GROUP OF PATIENTS WHO COULD BE ACHIEVING VERY LONG LASTING REMISSIONS AND IF 10 YEARS AFTER TREATMENT THERE'S NO DETECTABLE DISEASE THAT'S AS CLOSE AS WE MAY GET TO CURE IN CLL. FOR A SMALL SUBSET OF PATIENTS, IT MAY GIVE AN OPPORTUNITY OF DEALING WITH CLL DEFINITIVELY. YOU HAVE TO BE IN THE YOUNGER AGE GROUP. IT HAS TO BE IGHG MUE TATDED CLL SO THE PROGNOSTCALLY FAVORABLE CLL AND NO HIGH RISK MUTATIONS OR LESIONS BY FISH. SO FOR THAT GROUP, CHEMOTHERAPY MAY STILL PLAY A ROLE. WHEN YOU TALK ABOUT TRETTING NOR SECOND TIME, ESPECIALLY FOR ANYBODY WHO'S HAD CHEMOTHERAPY BEFORE, I THINK THE NEW TREATMENTS AND WE SAW SOME APPROVED AND ACALABRUTINIB HAS BEEN THERE SOME MANY YEARS AND AS A SECOND LINE OF TREATMENT. I WOULD STRONGLY SAY, IF NO TREATMENT IS NEEDED, NO TREATMENT SHOULD BE GIVING. SO WATCH AND WAIT. YOU MAY SAY THAT'S WATCH AND WORRY. I WOULD COUNTER, WELL, IT'S WATCH AND AVOID UNNECESSARY TREATMENT, UNNECESSARY COMPLICATIONS. THERE ARE TRIALS THAT TEST EARLY INTERVENTIONS AND WHETHER SOMEBODY THAT NEEDS TREATMENT IS BENEFICIAL. HONESTLY, I HAVE RESERVATIONS ABOUT THAT. IF WE USE ACTIVE TREATMENTS EARLY ON, SURELY THEY'LL BE ACTIVE. BUT WILL IT REALLY PREVENT LONG-TERM CONSEQUENCES LIKE SECOND CANCERS, RISK OF INFECTIONS. AND BEING ON A DRUG WILL ALWAYS HAVE SOME RISK OF SIDE EFFECTS. OUTSIDE OF A CLINICAL TRIAL, NO TREATMENT IS NEED. WHERE WE WOULD LIKE TO BE, MAYBE DOWN AT THE CHERRY BLOSSOMS. THERE'S STILL IN SEASON. WHAT ARE OUR GOALS? ONE IS TO FEEL WELL. WELL BEING IS AN IMPORTANT GOAL. CURE IS MAYBE THIS ELUSIVE GOAL FOR MANY CONDITIONS LIKE HYPERTENSION. WE DON'T CURE, WE MANAGE. AND FOR MANY DISEASES, FOR MANY CONDITIONS IN LIFE WE MANAGE AND DON'T NECESSARILY CURE. THEN THERE ARE PRACTICAL GOALS. AVOIDING TOXICITY. ESPECIALLY UNNECESSARY TOXICITY. AN ABSENCE OF COMPLICATIONS. WHICH ALSO MEANS ABSENCE OF COMPLICATIONS OF THE DISEASE AND IMPROVING IMMUNE FUNCTIONS AND INFECTIONS AND A LITTLE BIT OF TECHNICAL GOALS. REMISSION. MEANING, BASICALLY THE DISEASE IS EITHER INVISIBLE OR HEAVILY PUSHED BACK. WE HAVE M.R.D., WHICH IS ALMOST THIS NEW OR SURROGATE FOR CURE THAT I'LL SHOW YOU IS NOT A SURROGATE FOR CURE. AND THEN THE TIME LIMITED THERAPY THAT IS BECOMING ONE OF THE THINGS EVERYBODY SEEMS TO AIM FOR. LET ME GO OVER THE TECHNICAL GOALS. DEFINING THE GOALS. SO JUST SO WE KNOW WHAT WE'RE TALKING ABOUT. THE WHO CLASSIFICATION SAYS HEALTH SAY STATE OF COMPLETE, PHYSICAL, MENTAL AND SOCIAL WELL BEING. I'M NOT SURE HOW MANY DAYS A YEAR I'M REALLY HEALTHY BY THAT DEFINITION. AND PERMANENT IS HARD TO ASSESS. AND WE TALK ABOUT REMISSION WHICH IS THE NO VISIBLE DISEASE ON MEDICAL TESTING AND A PHYSICAL EXAMPLE, LABORATORY BASED AND THEN WE CAN INCREASE THE SOPHISTICATION OF LABORATORY BASED TESTING. LET ME SHOW YOU HERE WHAT WE THINK ABOUT WHEN WE TALK ABOUT REMISSION IN CLL. AT THE TIME A TYPICAL CLL PATIENT WOULD START TREATMENT, THERE ARE TRILLIONS OF CLL CELLS IN THE BODY. SO ROUGHLY THE EQUIVALENT OF THE NATIONAL DEBT IS PRESENT AS CLL CELLS IN THE BODY. SO ONCE HAVE YOU EFFECTIVE TREATMENT YOU REDUCE THAT BY 99%, SO THAT GETS US TO WHAT WE CALL A COMPLETE REMISSION. SO BY TYPICAL, CLINICAL TOOLS WE DON'T SEE ANY CLL. NOT ON A PHYSICAL EXAMPLE OR ROUTINE R ROUTINE LAB WORK. THE NEXT STEP DOWN IS THE MINIMAL RESIDUAL DISEASE NEGATIVE STATUS. THERE'S A LOT OF DEBATE IT'S A MISNOMER. FIRST OF ALL, DETECTION CUT-OFF MEANS 1 IN 10,000 WHITE CELLS IN THE BLOOD AND LESS THAN 1 IN 10,000 ARE CLL CELLS. IF WE GO BACK TO THE RELATIONSHIP FOR HOW MANY CLL CELLS ARE IN THE BODY WE STILL PROBABLY HAVE MILLIONS OF CELLS PRESENT AT THE TIME WE CALL THEM M.R.D. NEGATIVE. IT'S A DEEPER FORM OF DISEASE PUSHED BACK BUT IT'S NOT THE EQUIVALENT OF CURE. WHY SIT IMPORTANT? BECAUSE IN THE ERA OF CHEMOIMMUNOTHERAPY PATIENT WHO'S ACHIEVE THIS MRD NEGATIVE TYPE OF REMISSION HAD GOOD PROGRESSION THROUGH SURVIVAL. PROGRESSION-FREE SURVIVAL MEANS ON THIS CURVE YOU'RE ALIVE AND WELL. AND ON THIS YOU HAVE A HIGHER RISK OF DEVELOPING PROGRESSION. IN SOME WAYS IT SEPARATES PATIENTS BY EXPECTED OUTCOME. IF WITH THE SAME THERAPY YOU GET TO MRD NEGATIVE REMISSION IN SOME PATIENTS AND MRD, NOT MRD REMISSIONS IN OTHERS, IT'S BASICALLY A TEST FOR THE TYPE OF CLL SOMEBODY HAS. IT'S NOT JUST A MEASURE OF THE TREATMENT QUALITY. IT'S ALSO A MEASURE WHETHER IT'S A PROBLEMATIC TYPE CLL OR A CLL EASIER TO TREAT. AND THAT CONCENTRATION WILL BE IMPORTANT WHEN YOU LOOK AT NEW TREATMENTS. YOU MAY KNOW WILL VENETOCLAX IS ASSOCIATED WITH REMISSION OR A SMALL FRACTION OF PEOPLE THAT HAVE BEEN ON IBRUTINIB FOR MANY YEARS. WHAT I WANT TO SHOW YOU HERE IS THAT SENSE TOTALLY DIFFERENT TREATMENTS WHEN WE LOOK AT THE OTHER IMPORTANT OUTCOME, THEY HAVE A PROGRESSION-FREE SURVIVAL. ON THE CURVE BEING LOW AND ALIVE. WHEN THE IBRUTINIB PATIENTS TREATED DO PERFECTLY WELL EVEN THOUGH THERE IS DETECTABLE DISEASE. THEY STAY ON THIS CHRONIC THERAPY WHICH MANAGES THE CLL. IF WE LOOK AT THESE TWO CURVES THE ABILITY OF THE TREATMENT TO USE MRB NEGATIVE STATUS DOESN'T LONG TERM. AND I WANT TO SHOW YOU IS VENETOCLAX ALONE AND IBRUTINIB ALONE. NOW, WHEN THESE TWO ARE COMBINED AND THIS IS DATA FROM THE ANDERSON TRIAL WHERE THEY COMBINE IBRUTINIB AND VENETOCLAX. A VERY GOOD STUDY. VERY APPROPRIATE STUDY DONE FOR PATIENTS WITH HIGH-RISK CLL, DELETION 17P AND IMMUTE -- IMMUTE -- MU AND WHAT IS REMARKABLE HERE IS THAT TWO-THIRDS OF THE PATIENTS ACTUALLY HAVE MRB NEGATIVE STATUS. SO MEANING THERE IS A VERY DEEP LEVEL OF REDUCTION. SO WE'RE DOWN FROM TRILLIONS OF CELLS TO MILLIONS OF CELLS. THAT'S CERTAINLY GOOD. WHAT WE DON'T KNOW IS IF THE REMISSION WILL LAST AND IF THEY DON'T LAST, WHAT TYPE OF CLL IS COMING BACK. THE OTHER ASPECT IS ONCE WE START INTENSIFYING TREATMENT THE GROUP WE HAVE TO WORRY ABOUT ARE THOSE THAT DO NOT ACHIEVE THE GOOD RESPONSE. THIS PROBABLY IDENTIFIES THE TYPE OF CLL THAT NEEDS NEW APPROACHES AND NEEDS MODIFICATIONS OF THE TREATMENT PLAN. I WANT TO SHOW YOU HOW WE THINK ABOUT THIS AND YOU HEARD ABOUT CLINICAL TRIALS AND HOW WE WOULD STRUCTURE THIS. WHAT IS THE ROAD MAP WITH CLL AND IBRUTINIB IN PATIENTS WHO WERE TREATMENT NAIVE AND HAD NO P53 MUTATION THAT'S THE ORANGE LINE ON TOP OF. -- ON TOP. TO FIVE YEARS OUT, NOBODY'S RELAPSED. NOBODY'S DIED. EVERYBODY'S FINE. AND GETTING IT THROUGH THE ONCOLOGIST IS A PERFECTLY GOOD STRATEGY. THE GREEN CURVE THAT STARTS APPROACHING THE BOTTOM OF THE GRAPH ARE PATIENTS WITH RELAPSED CLL WHO HAVE DELETION 17P. WHILE MOST DO WELL FOR YEARS WITH TIME THE CLL STARTS TO FIND A WAY AROUND IT AND COMES BACK. THIS IS IDENTIFYING A GROUP OF PEOPLE WHO ARE PROBABLY BETTER SERVED IN EXPERT CENTERS AND WITH COMBINATION THERAPY. COMBINATION THERAP YES CAN COME IN DIFFERENT SHAPES AND FORMS. AND EVENTUALLY THERE NEEDS TO BE A CHANGE IN TREATMENT PLAN. I'M NOT SAYING EVERYBODY SHOULD START THE COMBINATION FROM THE GET GO. THERE'S A BALANCE BETWEEN RISK OF DEVELOPING RESISTANCE TO THE SINGLE AGENT AND WHAT IS CURRENTLY AVAILABLE AND THERE ARE WAYS OF SWEN SEQUENTIALLY ADDRESSING THE PROBLEMS AS THEY ARRIVE. THE GROUP IN THE MIDDLE ARE DELETION 17P AND MUTATIONS AND GOT IBRUTINIB AS THE FIRST TREATMENT AND THOSE IN THE MIDDLE ARE PATIENTS OLDER THAN 65 TREATED BEFORE BUT HAVE NO DELETION 17P. WE HAVE ONE GROUP THAT DOES PERFECTLY WELL NO MATTER WHAT YOU DO AS LONG AS YOU DON'T USE CHEMOTHERAPY. THE GROUP IN THE MIDDLE THAT MA WILL DO VERY WELL, THIS IS OUT TO FIVE YEARS. AND A GROUP WHO REALLY NEEDS NEW I IDEAS AND THAT'S WE BREAK IT DOWN AT THIS POINT. HOW LONG IS LONG-TERM THERAPY. IN OUR TRIAL 49 PATIENTS SO ABOUT 60% REMAINED ON STUDY WITH MORE THAN FIVE YEARS OBSERVATION TIME. IT SPANS 2011 THROUGH THE END OF 2017. THE MOST COMMON REASON WAS PROGRESSION. WE HAD FIVE PATIENTS WHO STOPPED DUE TO ADVERSE EVENTS. YOU WILL SEE THERE ARE REPORTS THAT HAVE MUCH MUCH HIGHER RATES OF DISCONTINUATION BECAUSE OF ADVERSE EFFECTS. OUR TRIAL WAS HEAVILY FOCUSSED THOSE WITH CLL. PATIENTS WERE VERY MOTIVATED. IT GAVE US TIME TO GET AROUND SIDE EFFECTS AND WORK THINGS OUT AND AFTER THE HUMP OF TWO TO SIX MONTHS ON THE DRUG, MOST PATIENTS ADVERSE EVENTS, SIDE EFFECTS BECOME MINIMAL OR TOLERABLE. AND HALF DISCONTINUED THE DRUG. SIX PATIENTS WITH CONSENT AND AND WE HAVE PATIENTS COMING FROM ALL OVER THE COUNTRY AND ONCE IBRUTINIB WAS APPROVED ALL OVER THE COUNTRY, SOME PATIENTS DECIDED NOT TO FLY HERE EVERY THREE TO FOUR MONTHS. THREE PATIENTS DIED FROM 2011 THROUGH 2017. IN OUR EXPERIENCE, LONG-TEM THERAPY WAS WELL ROLL TATED BY MOST. OUT OF WHAT YOU HAVE ALREADY SEEN BY WHAT CHRIS PRESENTED, WE SEE IMPROVEMENT IN IMMUNE FUNCTION ON IBRUTINIB. WE SEE IMPROVEMENTS IN HEME HEMOGLOBIN. AND HALF THE PATIENTS GET A SUBSTANTIAL INCREASE AND THESE PATIENTS HAVE FEWER INFECTIONS. WE CAN VACCINATE PATIENTS. THERE ARE WAYS TO FURTHER BUILD THE IMMUNE SYSTEM WHEN PATIENTS ARE ON THE TREATMENT. I THINK WE HAVE MANY ROADS WE CAN TAKE. SOMETIMES YOU HAVE CONVOLUTED ROADS AND NO MATTER WHICH ONE YOU PICK, IT MAY WELL BE AND BRIAN KOFFMAN SAID THIS VERY WELL, YOU EXPECT THE UNEXPECT. THERE IS A BREAK DOWN IN TRAFFIC AND YOU'RE STUCK. WHAT CAN HAPPEN IS THE CLL CELLS DEVELOP MUTATIONS AND YOU CAN GROW OUT AND IT LETS THEM RESIST. AND THE DOMINANT ONES IS IN BTK ITSELF. HOW IT BINDS TO BTK AND STAYS ATTACHED FOREVER. THE CELLS HAVE TO SYNTHESIZE AND HAVE TO MAKE A NEW ENZYME. IN THE RESISTANCE THIS ATTACHMENT OF IBRUTINIB IS LOST AND THE DRUG CANNOT WORK WELL ANYMORE. IN SOME WAYS IT'S DISAPPOINTING THERE ARE WAYS TO DEAL WITH IT. WE HAVE SEEN THE BENEFIT AND IMMUNE SYSTEM SEEMS TO BE PRESERVED AT THAT TIME AND THERE CAN BE STRATEGIES, IMMUNE BASED STRATEGIES TO OVERCOME THIS RESISTANCE. THAT'S A LITTLE BIT BEHIND WHY WE WOULD ADD ONE MEDICATION WITH IBRUTIN IBRUTINIB BUT ONE OF THE EFFECTIVE WAYS THAT'S AVAILABLE AND TALKED ABOUT AT THE TIME OF RESISTANCE IS CAR-T CELL THERAPY. THAT'S THE CHOICE BRIAN KOFFMAN MADE BY GOING FOR CAR LOVE T CELL THERAPY. AND YOU SEE AGAIN HERE YES, THE PLAN B HERE DOESN'T WORK FOR EVERYBODY BUT FOR THOSE WHO IT WORKS WELL, YOU SEE THE BLUE CURVE ON TOP, PATIENTS WHO HAD A COMPLETE RESPONSE TO THE CAR-T CELLS 18 TO 24 MONTHS OUT ARE NOT DOING WELL. THERE IS NO RIGHT ONE TO CHOOSE. WHAT I WOULD LIKE TO SHOW YOU HERE IS HOW ONE OF OUR PATIENT WHO PAINTED THIS AFTER BEING A YEAR OR TWO ON THE IBRUTINIB TRIAL. IN 2012, IT WAS THE LIFE SAFER FOR PEOPLE WITH DELETION 17P CLL OR HEAVILY PRE-TREATED CLL. THAT'S WHAT I THINK WE HAVE AT THIS POINT AND HOPE IN EVERY SITUATION WE GET INTO TREATING CLL BECAUSE WE HAVE A PLAN A AND FIT DOESN'T WORK WE HAVE A PLAN B. FIT DOESN'T WORK THERE'S MORE AND MORE OPTIONS WE CAN TURN TO. WE'RE HOPING THIS NEW TREATMENTS CAN HELP FIND A WAY FOR EVERYBODY AND I WOULD LIKE TO THANK PATIENTS WHO PARTICIPATE AFTER STUDIES AND WE DRAW A LOT OF BLOOD AND WE GET BONE MARROW DOOIP BIOPSIES AND WE LEARN A LOT FROM THEM. THANK YOU. >> PLEASE DO THE EVALUATIONS THAT WERE LEFT AND YOU CAN GIVE THOSE TO NANCY AND DEBORAH OR MYSELF AND IF THOSE PEOPLE CAN STAND UP AND HAND THOSE OFF AND WE HAVE TO PRESENT THOSE TO THE SPONSORS TO SAY WE GOT SOMETHING OUT OF THE CONFERENCE. ANY FEEDBACK, ANYTHING WE SHOULD BE DOING DIFFERENTLY, DON'T BE SHY TO POINT OUT WHAT WE COULD BE DOING BETTER. IF YOU WANT TO PASS BACK THE ENVELOPE THAT'S HELPFUL. IF YOU WANT TO FIND OUT ABOUT THE TOOL KITS FOR YOUR HEMATOLOGIST, I COULD HELP OUT AND WE CAN GET MORE TO YOU IF IT'S HELPFUL. I WANT TO THANK EVERYONE FOR COMING BECAUSE IT'S THE START AND HOPEFULLY TO BE CONTINUED. ARE THERE ANY QUESTIONS PEOPLE HAVE? PLEASE. >> WITH RESPECT TO THE RECENT OUTBREAK OF MEASLES ARE WE AT HIGHER RISK AND WHAT'S OUR RISK PROFILE FOR EXPOSURE AND I HAVE GRANDCHILDREN CONSTANTLY GETTING VACCINES AND WHAT'S THE PROTOCOL IF YOU CAN ADDRESS THOSE ISSUES. >> SOME STUDIES HAD TO BE RETRACTED FOR THE MMR, THE MEASLES VACCINE WHERE THERE WAS A THOUGHT IT FUELED AUTISM, WHICH IS WRONG. IT STILL CIRCULATES WIDELY ON THE INTERNET AND THE VACCINE RATES ACROSS THE WORLD ARE FALLING. THAT PUTS US AT INCREASED RISK IN GENERAL AND IN GENERAL THE PATIENTS THAT ARE AT MOST RISK ARE THE VERY YOUNG, INFANTS AND CHILDREN AND ELDERLY AND IMMUNOCOMPROMISED. FOR MEASLES AS WELL, IF YOU HAD THE DISEASE OR VACCINE BEFORE, YOU ARE USUALLY PROTECTED. THE UNKNOWN QUESTION IS IN CLL WHERE WE FRANKLY DON'T QUITE KNOW BECAUSE THE IMMUNE SYSTEM WANES. WE THINK HE -- THE RISK IS LOW. >> GENERALLY THE RESPONSE IN CLL IS MAKING NEW ANTIBIOTICS -- ANTIBODIES TO NEW THINGS. GENERALLY THE OLD ANTIBODIES WE HAVE FROM THE DISEASES WE HAD AS KIDS OR SHOTS AS KIDS ARE USUALLY PRETTY GOOD. NOT AS GOOD AS SOMEONE WHO DOESN'T HAVE CLL BUT PRETTY GOOD. IT'S THE NEW THINGS WE HAVE TROUBLE WITH MAKING AND THAT'S WHY THEY'RE STUDYING THE FLU OR HEP B AND THE SHINGLES AND MOST OF US AS I LOOK AROUND HAD CHICKEN POX BUT CHICKEN POX IS DIFFERENT BECAUSE IT STAYS DORMANT IN THE BODY. IF YOU TEST TIDERS WE HAVE THE OLDER ANTIBODIES SO IT'S A DIFFERENCE EXPERIENCE. GENERALLY. THAT'S WAY OVER SIMPLIFYING IT. >> A QUESTION FOR DR. KOFFMAN. IS THERE A NUMBER FOR THE CLL SOCIETY SO FEDERAL EMPLOYEES CAN HAVE DONATIONS FROM THEIR PAYCHECKS? >> NOT THAT I KNOW OF BUT TALK TO ME AFTERWARDS. I WOULD LOVE TO BECAUSE WE'RE A REGISTERED 5013C WE HAVE MATCHING FUNDS WITH OTHER ORGANIZATIONS BUT I'D LOAF -- LOVE TO KNOW ABOUT THAT. >> IS THERE A RECOMMENDATION IBIG PATIENTS NOT GET THE TWO VACCINES BECAUSE WE DON'T KNOW IF IT WILL BE EFFECTIVE OR SHOULD WE GET THEM ANYWAY? >> SO THE REASON WHY WE INCLUDE THE IBIG IS HOW WE MEASURE THINGS. WHAT WE'RE TESTING FOR AND LOOK FOR IS THE ANTIBODY RESPONSE BUT WE RECOMMEND PATIENTS FOR VACCINES. SO THE IVIB DOESN'T INTERFERE WITH THE EFFECTIVENESS OF THE VACCINE BUT INTERFERES HOW TO MEASURE YOUR IMMUNE RESPONSE AND IT'S A SURROGATE FOR ACTUAL INFECTION. WE WANT REDUCED INFECTION AND THE VACCINE WILL HLP. >> AND AGAIN, THE SOONER YOU GET YOUR VACCINE, THE IMMUNITY DOES NOT GENERALLY GET BETTER THE LONGER YOU HAD CLL. CAR-T FOR RETITUXIMAB INTERFERES WITH YOUR ABILITY TO MAKE ANTIBODIES SO THE SOONER YOU GET IT THE BETTER. >> CAN YOU COMMENT ON PATIENTS WITH CLL BEING AROUND CHILDREN GETTING LIVE VIRUS VACCINES? IF I'M NOT MISTAKEN, THOSE PATIENTS WILL SHED VIRUS FOR A CERTAIN AMOUNT OF TIME AFTER THEY'RE VACCINED. -- VACCINE -- VACCINATED. >> YOU'RE ASKING THOSE PATIENTS TREATED WITH THE VACCINE IS THERE A CHANCE -- >> I THINK HE'S ASKING YOUR GRANDKIDS GET THEIR MMR AND YOUR CHILDREN ASK YOU TO BABYSIT THEM THE NEXT DAY, CAN YOU DO THAT? WHAT'S YOUR RISK BECAUSE THEY CAN BE SHEDDING THAT VARIETY OF THE LIVE VACCINE. WHAT'S THE RISK TO THE IMMUNE COMPROMISED PATIENT WHEN THEY'RE CHILDREN OR GRANDCHILDREN HAVE A LIVE VACCINE. >> IF YOU CAN DO THAT WITHOUT DISRUPTING THE FAMILY, THEN DO IT. WE ALSO GET THE QUESTION SHOULD WE AVOID IF SOMEBODY HAS A COLD. I'M ALWAYS ON THE SIDE OF TRYING TO ADVISE NOT TO CHANGE YOUR LIFE. USE A HAND SANITIZER AS MUCH AS POSSIBLE. >> I KNOW THERE WAS A SHORT FLY SPLOOI OF THE VACCINE AND THERE WAS A SHORT SUPPLY OF THE VACCINE AND IF NOT CAN WE GET IT FOR NIH. >> THE SHIB -- SHINGRIX WAS A VICTIM OF THEIR OWN SUCCESS. THE CDC RECOMMENDED TO GET IT EVEN IF THEY RECEIVED THE OLD VACCINE. THE COMPANY DIDN'T THINK THE CDC WOULD RECOMMEND THAT OVER ANY OTHER VACCINE. THAT CAUSED A HUGE DEMAND. AND IN FACT THEY NEEDED TO SEIZE THEIR ADVERTISING AFTERWARDS BECAUSE THEY WERE IN HUGE BACKLOG. THE SUPPLY IS EASING SLOWLY. WE NOTICED MORE SHIPMENTS TO DIFFERENT HOSPITALS SO THE BEST WAY IS TO DIRECTLY CALL YOUR LOCAL PHARMACY OR HEALTH CARE INSTITUTION AND ASK THEM IF THEY HAVE THE VACCINE IN SUPPLY. >> AT THE NIH WE'RE TRYING TO GET IT ON THE FORMULARY. THEN THEY CAN BE GENERALLY GIVEN TO ANY PATIENTS. THAT REQUEST HAS BEEN APPROVED BUT A LITTLE BIT ON HOLD BECAUSE WE CAN'T GUARANTEE VACCINE DOSES IN PATIENTS OUTSIDE THE CLINICL TRIALS. SO WE CURRENTLY ONLY HAVE VACCINES TO VACCINATE THOSE ON THE CLINICAL TRIAL. WE'RE HOPING IN THE FUTURE WE WILL BE ABLE TO DO THAT. THAT'S STILL PENDING. >> AND IF YOU CURRENTLY SOURCE CLL EXPERTS AND RECOMMENDATION FOR CLL PATIENTS YOU'LL GET HALF SPLIT. SOME WILL SAY, SURE, VACCINATE, OTHERS WILL SAY IT WILL NOT WORK. WE ACTUALLY DON'T KNOW HOW WELL THE VACCINES WORK IN CLL PATIENTS. WE LESS KNOW HOW WELL THEY CAN WORK ON IBRUTINIB BECAUSE IT'S A LONG-TERM THERAPY, I THINK IT'S AN IMPORTANT QUESTION. THAT'S WHY WE SET UP THIS TRIAL AND I THINK WE DEFEND ON PEOPLE PARTICIPATING ON THAT SO WE CAN INFORM PATIENTS IF IT WORKS AS WELL AS OTHER AND MAYBE LESS WELL. >> ALL OF US ARE AFFECTED BY THE FOOD WE PUT IN OUR MOUTH SO IS ARE THERE SUPPLEMENTS BENEFICIAL FOR CLL PATIENTS OR ON THE OTHER HAND, DETRIMENTAL? >> LET ME ANSWER THAT. THERE'S NO DIET I KNOW OF THAT WILL CURE YOUR CLL. BUTPEOPLE WITH CANCER HAVE HIGHER RISK OF HEART DISEASE AND PEOPLE WITH HEART DISEASE HAVE A HIRE RISK OF CANCER IT'S WITH INFLAMMATION. THE MEDITERRANEAN DIET YOUR INTERNIST WOULD CAUSE TO YOU HAVE MORE OF A PLANT-BASED DIET WITH COLD WATER FISH IS HELPFUL. THE WAY I LOOK AT IT IS I ALREADY HAVE CLL. I DON'T WANT TO ALSO HAVE A HEART PROBLEM. I'M TAKING IBRUTINIB WHICH INCREASES YOUR RISK OF HEART CONDITIONS. THERE'S CLEAR EVIDENCE A MEDITERRANEAN DIET LOWERS YOUR RISK OF HEART PROBLEMS. THERE WAS A STUDY OUT OF SPAIN THAT SHOWED A MEDITERRANEAN DIET HELP PEOPLE WITH CLL MORE THAN TYPICAL AMERICAN DIET. THAT BASIC DIET APPROACH. IN TERMS OF SUPPLEMENTS, THE TWO THAT HAVE BEEN STUDIED THE MOST CLOSE CLOSELY ARE TURMERIC IN THE LAB IT'S VERY EXCITING. I DON'T KNOW THERE'S MUCH CLINICAL EVIDENCE OF VALUE. I'LL LET THE TWO OTHER DOCTORS COMMENT ON THE GREEN TEA EXTRACT BECAUSE THAT'S THE OTHER HOT SUPPLEMENT THAT PEOPLE SOMETIMES USE. >> AN HEALTHY DIET EVEN TRYING TO BE MORE UNHEALTHY BUT TRYING TO USE FOOD AS A THERAPEUTIC PRINCIPLE IS DIFFICULT. IF PEOPLE START PUSHING THAT, THERE'S PROBABLY TOO MUCH OIL IF YOU TAKE TOO MUCH OF THAT. IT CAN AFFECT PLATELET FUNCTION AND INCREASED RISK OF BRUCING AND INCREASED RISK OF COMPLICATIONS OF DRUG INTERACTIONS ESPECIALLY WITH THE UNAPPROVED FOOD SUPPLEMENT. SO HEALTHY DIET IS GREAT. VITAMIN SUPPLEMENTS ARE PROBABLY ALSO GREAT BUT THERE STARTS TO BE A GRAY ZONE WHERE SOME OF THE REMEDIES CAN BECOME PROBLEMATIC. >> CAN YOU COMMENT ON GREEN TEA EXTRACT. I NOTICED YOU AVOIDED THAT. >> I KNOW PEOPLE WHO DRINK GREEN TRA TEA. I THINK THE STUDIES PEOPLE REFER TO IS ACTUALLY NOT EASILY AVAILABLE >> THERE WAS A GREEN TEA EXTRACT AND I THINK IT'S AN AVAILABILITY PROBLEM. >> THE STUDY OUT OF MAYO USES A SPECIFIC TYPE OF GREEN TEA EXTRACT AND IT'S NOT COMMERCIALLY AVAILABLE. IT'S EFFECTS WERE MODERATE. I'M NOT SAYING THERE WERE EFFECTS BUT THEY WERE RELATIVELY MODERATE AND GENERALLY IN THE MORE SLOW GROWING CLL IS WHERE IT SEEMED TO STABILIZE THINGS FOR SOME PATIENTS. AND IF YOU'RE 17P DELETED I WOULD NOT RELY ON GREEN TEA EXTRACT BUT IF YOU WANT TO DO GREEN TEA AND A PLANT-BASED DIET AND REGULAR EXERCISE, GOOD NIGHT'S SLEEP, YOU SHOULD BE DOING ALL OF THAT STUFF. I THINK WE'RE A LITTLE OVER TIME. I WANT TO THANK EVERYBODY AND THANK THE NATIONAL INSTITUTES OF HELP AND DR. REISNER HAS BEEN AN INCREDIBLE PARTNER AND THE WHOLE TEAM. IT WAS AN INCREDIBLE PRESENTATION. IT WILL BE ARCHIVED AND I WILL HANG FOR A FEW MINUTES. MAKE SURE I GET THE EVALUATIONS IN THE ENVELOPES AND ANY QUESTIONS, WE'LL HANG OUT A FEW MINUTES.