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>> GOOD AFTERNOON EMPLOY
MY NAME

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IS EDCALLAN AT NIAMS AND IT'S MY

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GREAT PLEASURE TO WELCOME YOU TO

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TODAY'S CLINICAL CENTER

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CONTEMPORARY MEDICINE GREAT

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TEACHERS GRAND ROUNDS.

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THE CME ACTIVITY CODE FOR

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HOPKINS IS 50544, PLEASE TEXT

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THIS CODE TO THE PHONE NUMBER ON

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THE SLIDE TO RECEIVE CME CREDIT

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FOR THIS LECTURE, WE ALSO INVITE

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TO YOU PROVIDE FEEDBACK ON

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TODAY'S LECTURE BY SCANNING THE

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QR CODE ON THE CME SLIDE, FOR

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THOSE AMRIING FOR CME WILL

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RECEIVE A FEEDBACK LINK VIA

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E-MAIL THAT WILL BE USED TO

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PROVIDE FEEDBACK ABOUT THIS

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PRESENTATION AND ALLOWS TO YOU

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SUBMIT ANY SUGGESTION FOR FUTURE

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GRAND ROUNDS TOPICS, YOU MAY

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SUBMIT QUESTIONS DURING THIS

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LECTURE BY CONTROLLING DOWN AND

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CLICKING THE--SCROLLING DOWN AND

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CLICKING THE LIVE FEEDBACK

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BUTTON ON THE WEBSITE.

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QUESTIONS WILL BE TAKEN AS TIME

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PERMITS.

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TODAY WE ARE EXCITED TO ANNOUNCE

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DR. YOUN KIM, WORKING AT

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STANFORD UNIVERSITY SCHOOL OF

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MEDICINE AND DIRECTOR OF

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STANFORD'S MULTIDISCIPLINARY CUE

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TAINIOUS LYMPHOMA PROGRAM.

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DR. KIM RECEIVED HER BACHELOR'S

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IN WELSY COLLEGE AND EARNED HER

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MEDICAL DEGREE FROM STANFORD

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SCHOOL OF MEDICINE AND COMPLETED

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AN INTERN HELP AT KAISER

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PERMANENT AT SAN FRANCISCO AND

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REPORTING RESIDENCY IN

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DERMAATOLOGY AT STANFORD.

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THE STANFORD MULTIDISCIPLINARY

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CUE  CUTEAINIOUS LYMPHOMA, NOVEL

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DISCOVERY AND SHE AND HER

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COLLEAGUES ARE EVALUATING A

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NUMBER OF CUTTING EDGE

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MODALITIES INCLUDING CELL

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THERAPY, VACCINATION, IMMUNE

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CHECK POINT BLOCKADE AND ALOE

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GENERATED AIC HEMATOPOIETIC STEM

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CELL TRANSPLANT.

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DR. KIM HAS AUTHORED OVER 200

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ARTICLES AND HAS BEEN A

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PRINCIPAL OR CO INVESTIGATOR ON

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OVER 40 CLINICAL TRIALS.

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SHE HAS LED KEY CONSENSUS

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PROJECTS IN THE PRACTICE OF

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LYMPHOMA, MANAGEMENT AND SHE'S

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GLOBAL CO LEADER OF THE

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CUTANEOUS LYMPHOMA INTERNATIONAL

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CONSORTIUM. 

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SHE ALSO SERVESOT CUTANEOUS

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BOARD, SHE HAS ALSO EARNED THE

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JAMES MARK AWARD FOR EXCELLENCE

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IN PATIENT CARE AND THE

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DISTINGUISHED SERVICE AWARD FROM

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THE DEPARTMENT OF DERMATOLOGY,

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HER TALK IS ENTITLED INTEGRATING

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NEWER THERAPIES IN ADVANCED

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SPEAKER CTL.

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PLEASE WELCOME OUR SPEAKER

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DR. YOUN KIM.

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>> THANK YOU SO MUCH DR.
CALLAN,

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I WILL SHARE MY SCREEN.

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TRUSTEES YOU GO SO HOPEFULLY YOU

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HAVE MY SLIDES.

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THANK YOU.

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I WANT TO THANK DR. COWEN FOR

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THIS INVITATION AND IT'S A GREAT

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PLEASURE AND PRIVILEGE TO

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ADDRESS ALL THE MENTORS,

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COLLEAGUES AND TRAINEES AT THE

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NE H AND I MET THE MRSP MENTEES

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THIS MORNING, IT WAS IMPRESSIVE

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GROUP OF FUTURE LEADERS AND I'M

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SO DPLAD THAT NIH IS SUPPORTING

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SUCH TRAINING.

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SO TODAY EMBRACE YOUR TIME, I

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WILL BE TALKING ABOUT A REALLY

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RARE DISEASE GROUP CUTANEOUS

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T-CELL LYMPHOMA, SPECIFICALLY

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MYCOSIS, FUNNINGOIDS AND SEZARY

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SYNDROME.

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WE'VE MADE THERAPEUTIC ADVANCES

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AND HOW WE CAN HELP OUR

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PATIENTS.

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MY DISCLOSURES.

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AND BRIEFLY THE LEARNING

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OBLIGATIONS YECTIVES THIS

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MORNING WOULD BE TO HELP YOU

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APPRECIATE THE HETEROGENEITY,

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CLINICALLY, PATHOLOGICALLY AND

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GENETICALLY IN THIS RARE DISEASE

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GROUP AND HOW TREATMENTS THAT WE

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HAVE, WORK VERY DIFFERENTLY IN

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DIFFERENT DISEASE COMPARTMENTS

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AND THE SKIN,  LYMPHNODE AND

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BLOOD AND WE HAVE TO WORK BETTER

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AT ALIGNING PEASHTS WITH THE

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TREATMENT PROFILE AND HOW WE GO

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ABOUT DOING HAD AND HOW WE NEED

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TO MAKE MUCH MORE PROGRESS IN

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THE FUTURE.

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IN ORDERED TO DO THIS, IT IS

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VERY VITAL THAT WE WORK AS A

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COLLABORATIVE GROUP,

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INTERDISCIPLINARY AND IN

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CUTANEOUS LYMPHOMA THE DISPLENS

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THAT ARE MORE RELEVANT WOULD BE

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DERMATOLOGY, MEDICAL ONCOLOGY,

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MEDICINE, CELL THERAPY,

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RADIATION ONCOLOGY, MORE MAN

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SURGICAL ONCOLOGY AND THEN

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PATHOLOGY FOR DIAGNOSTICS AND

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OUR OTHER PARTNERS.

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THIS IS OUR MULTIDISCIPLINARY

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GROUP, LEADERS AT STANFORD, NOT

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ONLY DID IT SHOW THAT WE HAVE

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KEEP PICTURES WHEN WE WERE

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YOUNGER, BUT WE DO HAVE LEADERS

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THAT ALSO HAVE OUR COLLABORATIVE

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PARTERS WITHIN, SO WE HAVE

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DERMATOLOGY, RADIO ONCOLOGY,

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CELL THISSER ACTIVITIES AND

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PROJECTSY TRANSPLANT PART MERAND

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IMPORTANTLY MICHAEL KHODADOUST

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IS OUR TRANSLATIONAL RESEARCH

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LEAD AND MEDICAL ONCOLOGY

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PARTNER.

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I WILL START WITH A LITTLE

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OVERVIEW FOR THOSE WHO DO NOT

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KNOW CTCL WELL.

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[INDISCERNIBLE] MAKE UP A

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MAJORITY OF THE CTCLAND IT'S

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STILL IN THE RARE ORPHAN DISEASE

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CATEGORY, IT'S UNIQUE IN THAT

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THE CLINICAL DISEASE AND HIGHLY

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HETEROGENIUS NOT ONLY WITHIN THE

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PRIMARY SKIN COMPARTMENT BUT

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ACROSS THE EXTRA CUE TAINIOUS

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COMPARTMENTS, BEYOND THE

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INTERPATIENT DIFFERENCES THERE'S

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NOTABLE INTRA PATIENT

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VARIABILITY WHERE WITHIN A

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PATIENT THERE COULD BE A MIX OF

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PATCH LIKE TUMORS AND THERE

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COULD BE MIXED RESPONSES OF A

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TREATMENT ACROSS ALL THESE TYPE

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OF SKIN LESION ANDS COMPART AMS.

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AND TO ADD TO THE CHALLENGE IN

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THIS RARE DISEASE WITH

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HETEROGENEITY, WE OFTEN LACK

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ROBUST DATA BECAUSE IT IS A RARE

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DISEASE, SO EVIDENCE BASED

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DECISION MAKING IS QUITE

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CHALLENGING AT TIMES AND WE HAVE

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TO PERSONALIZE TO THE MAXIMUM OF

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TREATMENT, IT'S VERY HIGHLY

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INDIVIDUALIZED.

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IN ADDITION TO THE CLINICAL

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HETEROGENEITY, PATIENTS OFTEN

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HAVE A DIVERSE PROFILE OF

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HISTOPATHOLOGY, WITH LESION TO

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LESION IMMUNO TYPIC VARIABILITY

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WITHIN A PATIENT.

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AT THE GENETIC LEVEL WE OBSERVE

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NOTABLE HETEROGENEITY ACROSS

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PATIENTS AND PATIENT'S GENETIC

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DATA OR GENOMIC TESTING HAS NOT

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SERVED AS A USEFUL CARE STANDARD

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AT THIS TIME, HOWEVER, WITHIN

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THE HETEROGENEITY THERE ARE

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COMMONALITIES THAT SHARE

185
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MECHANISM ANDS PATHWAYS, FOR

186
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EXAMPLE, IN THE T-CELL SPECIFIC

187
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PATHWAYS LIKE THE TCR,

188
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SIGNALING, AND THUS IN THE

189
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FUTURE WE HOPE WE WOULD HAVE

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MORE MOLECULARLY TARGETED

191
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THERAPIES AND GUIDES.

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BECAUSE OF THE HETEROGENEOUS ORY

193
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GENERATED AITY LARGELY WHAT

194
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DIRECTS OUR MANAGEMENT AND

195
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CLINICAL FACTORS AND CLINICAL

196
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STAGE.

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DISEASE SEVERITY IN THE

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COMPARTMENTS, SKIN AND EXTRA

199
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CUTANEOUS DEPARTMENTS AND

200
00:08:02,905 --> 00:08:05,575
PRESENCE OF WHAT WE CALL LARGE

201
00:08:05,575 --> 00:08:06,576
CELL TRANSFORMATION WHERE

202
00:08:06,576 --> 00:08:09,245
DISEASE BECOMES MORE AGGRESSIVE,

203
00:08:09,245 --> 00:08:15,051
WITH LARGE CELL AND MORE HIGH

204
00:08:15,051 --> 00:08:15,485
PROLIFERATIVE INDEX.

205
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THOSE GUIDE OUR MANAGEMENT.

206
00:08:17,353 --> 00:08:18,888
THE CLINICAL RISK STRATIFICATION

207
00:08:18,888 --> 00:08:22,558
APPROACH IS SUPPORTED BY OUR

208
00:08:22,558 --> 00:08:26,562
LARGE COLLABORATIVE PROJECT IN

209
00:08:26,562 --> 00:08:30,466
THE ADVANCED MS AND SS IN THE

210
00:08:30,466 --> 00:08:31,801
CONSORTIUM WHICH OOH DEBTIFYS

211
00:08:31,801 --> 00:08:33,569
LOW, MEDIUM AND HIGH RISK

212
00:08:33,569 --> 00:08:34,971
CATEGORIES OF PASHTS WHERE THE

213
00:08:34,971 --> 00:08:37,140
HIGHER RISK PATIENTS WE ARE MORE

214
00:08:37,140 --> 00:08:37,640
ALIGNED WITH AGGRESSIVE

215
00:08:37,640 --> 00:08:39,509
THERAPIES AND THE LOWER RISK AND

216
00:08:39,509 --> 00:08:44,714
WITHIN THE ADVANCED DISEASE

217
00:08:44,714 --> 00:08:48,317
EMPLOY IN THE EARLY STAGE

218
00:08:48,317 --> 00:08:49,819
DISEASE, SKIN-DIRECTED THERAPIES

219
00:08:49,819 --> 00:08:52,455
PLAY A LARGE ROLE, AND SYSTEMIC

220
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THERAPIES ARE RE7ED MORE FOR

221
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THOSE REFRACTORY FOR SKIN

222
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THERAPIES, OR IN THE ADVANCED

223
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DISEASE.

224
00:09:01,264 --> 00:09:04,033
ALSO UNIQUE IN CT CELL IS THE

225
00:09:04,033 --> 00:09:05,668
UTILITY OF TOTAL SKIN ELECTRON

226
00:09:05,668 --> 00:09:08,071
BEAM WHERE YOU CAN GIVE

227
00:09:08,071 --> 00:09:09,372
RADIATION TO THE ENTIRE SKIN

228
00:09:09,372 --> 00:09:11,007
SURFACE AND YOU CAN SEE IN THIS

229
00:09:11,007 --> 00:09:15,178
PATIENT, IT COULD BE HIGHLY

230
00:09:15,178 --> 00:09:17,080
EFFICIENT AND DEBULKING THE SKIN

231
00:09:17,080 --> 00:09:18,948
DISEASE AND RADIATION STILL

232
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REMAINS AS THE MOST SINGLE

233
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RELIABLE THERAPY DESPITE ALL THE

234
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MEDICAL THERAPY ADVANCES SO

235
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RADIATION IS A VERY IMPORTANT

236
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COMPONENT.

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IN THE ADVANCED DISEASE, THE

238
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LARGE CELL TRANSFORMATION, AS I

239
00:09:30,860 --> 00:09:33,663
ALLUDED TO IS A VERY IMPORTANT

240
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FACTOR BECAUSE IT IS SOSHT WIDE

241
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MORE AGGRESSIVE BEHAVIOR AND

242
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THAT THUS IT WILL LEAD TO US

243
00:09:45,308 --> 00:09:46,142
INTENSIFYING THERAPY EARLIER.

244
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DEC STATUS AND SEVERITY OF THE

245
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EXTRA CUE TINIOUS DEPARTMENTS,

246
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LYMPHNODE, VISCERA, BLOOD, ALL

247
00:09:52,715 --> 00:09:56,452
DICTATE TREATMENT CHOICES, GIVEN

248
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THAT COMBINATION THERAPIES AS

249
00:09:58,121 --> 00:10:00,690
COMBINATION CHEMO THERAPYS THAT

250
00:10:00,690 --> 00:10:05,094
ARE USED IN SYSTEMIC T-CELLS AND

251
00:10:05,094 --> 00:10:07,964
LYMPHOMAS, GIVE SHORT RESPONSE,

252
00:10:07,964 --> 00:10:09,065
SINGLE SYSTEMIC THERAPIES ARE

253
00:10:09,065 --> 00:10:10,500
STILL THE MAIN MODALITY AND THE

254
00:10:10,500 --> 00:10:12,735
ADVANCED DISEASE TO GET MORE

255
00:10:12,735 --> 00:10:14,203
LONG-TERM UTILITY AND MILEAGE

256
00:10:14,203 --> 00:10:16,172
OUT OF OUR THERAPIES AND

257
00:10:16,172 --> 00:10:17,173
COMBINATION THERAPIES ARE USED

258
00:10:17,173 --> 00:10:23,279
MORE TO BRIDGE TOWARDS AN ALALOE

259
00:10:23,279 --> 00:10:24,847
GENERATED AIC TRANSPLANT.

260
00:10:24,847 --> 00:10:30,553
THE UNICK QUALITIES OF PATIENTS

261
00:10:30,553 --> 00:10:32,188
CHALLENGES, NOT ONLY WITH THE

262
00:10:32,188 --> 00:10:33,623
VISUAL ASPECT THAT DEBILITATES

263
00:10:33,623 --> 00:10:35,391
BUT THE ITCHING AND PAIN THAT

264
00:10:35,391 --> 00:10:37,460
OUR PATIENTS SUFFER REQUIRING

265
00:10:37,460 --> 00:10:38,661
INTENSIVE SKIN CARE ISSUES IT'S

266
00:10:38,661 --> 00:10:40,396
VERY DEMANDING ON THE PATIENT

267
00:10:40,396 --> 00:10:41,931
AND THE FAMILY, THUS QUALITY OF

268
00:10:41,931 --> 00:10:45,268
LIFE ELEMENTS MAY LEAD TO

269
00:10:45,268 --> 00:10:46,669
DECISION TO CHANGE TREATMENT

270
00:10:46,669 --> 00:10:50,072
BEFORE AN OBLIGATIONS YECTIVE

271
00:10:50,072 --> 00:10:51,507
DISEASE PROGRESSION, THIS

272
00:10:51,507 --> 00:10:52,742
COMPLICATING OUR DEC PROGRESSION

273
00:10:52,742 --> 00:10:53,876
SURVIVAL TYPE OF DATA.

274
00:10:53,876 --> 00:10:54,944
IT'S IMPORTANT TO INTEGRATE THE

275
00:10:54,944 --> 00:10:57,079
QUALITY OF LIFE TOOLS IN OUR,A

276
00:10:57,079 --> 00:11:00,249
ASSESSESMENT OF MEANINGFUL

277
00:11:00,249 --> 00:11:01,184
THERAPIES, TO OPTIMIZE

278
00:11:01,184 --> 00:11:02,385
SUPPORTIVE CARE TO IMPROVE

279
00:11:02,385 --> 00:11:06,122
QUALITY OF LIFE IS ESSENTIAL.

280
00:11:06,122 --> 00:11:09,158
SO MEANINGFUL, THERAPIES, IN OUR

281
00:11:09,158 --> 00:11:11,794
DISEASE AND CTCL IS COMPOSED OF

282
00:11:11,794 --> 00:11:14,096
A TREATMENT THAT CAN GIVE

283
00:11:14,096 --> 00:11:15,631
DURABLE RESPONSE, SO NOT

284
00:11:15,631 --> 00:11:16,732
COMPLETE RESPONSE THAT LASTS A

285
00:11:16,732 --> 00:11:18,301
MONTH BUT WE WANT A GOOD

286
00:11:18,301 --> 00:11:21,270
RESPONSE THAT'S MORE DURABLE.

287
00:11:21,270 --> 00:11:22,972
AND BECAUSE A DISEASE IS MORE

288
00:11:22,972 --> 00:11:26,342
CHRONIC WE NEED ACCEPTABLE

289
00:11:26,342 --> 00:11:27,810
CUMULATIVE TOXICITY, AND NOT

290
00:11:27,810 --> 00:11:31,981
JUST A SHORT-TERM DLT, THAT ARE

291
00:11:31,981 --> 00:11:34,851
IMPORTANT IN TRIALS BUT

292
00:11:34,851 --> 00:11:36,552
CUMULATIVE THEY CAN TOLERATE

293
00:11:36,552 --> 00:11:38,087
OVER LONG PERIODS OR RETREATMENT

294
00:11:38,087 --> 00:11:39,121
AND IMPROVE LIFE QUALITY.

295
00:11:39,121 --> 00:11:46,028
SO A BALANCE OF ALL  3 FACTORS

296
00:11:46,028 --> 00:11:46,996
CONSTITUTES A SUCCESSFUL

297
00:11:46,996 --> 00:11:51,901
MEASUREMENT OF THERAPY IN CTCL. 

298
00:11:51,901 --> 00:11:53,035
THIS IS IMPORTANT BECAUSE

299
00:11:53,035 --> 00:11:54,971
OBVIOUSLY OUR DISEASE IS MORE OF

300
00:11:54,971 --> 00:11:57,406
A CHRONIC THAN PAN KRISTATTIC CA

301
00:11:57,406 --> 00:12:01,210
WHERE OVERALL SURVIVAL MAY BE

302
00:12:01,210 --> 00:12:02,612
THE PRIMARY END POINT.

303
00:12:02,612 --> 00:12:04,280
SO IN TERMS OF LANDSCAPE OF

304
00:12:04,280 --> 00:12:05,815
TREATMENT, WE'VE HAD A LOT OF

305
00:12:05,815 --> 00:12:08,885
PROGRESS OVER THE LAST DECADE,

306
00:12:08,885 --> 00:12:11,787
STARTING FROM THE MOLECULAR

307
00:12:11,787 --> 00:12:14,323
DRIVERS THAT'S BEEN DECODED AND

308
00:12:14,323 --> 00:12:17,493
IN 2015 THERE ARE MANY SERIES OF

309
00:12:17,493 --> 00:12:20,496
PUBLICATION THAT DRIEB THE

310
00:12:20,496 --> 00:12:22,365
MOLECULAR PATHOGENESIS IN CTCL,

311
00:12:22,365 --> 00:12:25,768
STARTING WITH THAT, WE WERE ABLE

312
00:12:25,768 --> 00:12:31,707
TO DO MORE MOLECULARLY OR

313
00:12:31,707 --> 00:12:32,575
BIOMARKER TARGETED THERAPIES.

314
00:12:32,575 --> 00:12:34,844
WE COULD DESCRIBE OUR THERAPIES

315
00:12:34,844 --> 00:12:36,612
IN CTCL IN TARGETING 3 AREAS,

316
00:12:36,612 --> 00:12:38,848
FIRST WOULD BE THE SURFACE

317
00:12:38,848 --> 00:12:42,985
TARGETS AND WE HAVE A LOT OF

318
00:12:42,985 --> 00:12:44,220
PROGRESS IN IDENTIFYING SPECIFIC

319
00:12:44,220 --> 00:12:46,689
SURFACE TARGETS OF THE CTCL

320
00:12:46,689 --> 00:12:50,293
CELLS AND STREAM OF ANTIBODIES,

321
00:12:50,293 --> 00:12:52,328
AND OTHER SURFACE TARGETED

322
00:12:52,328 --> 00:12:55,798
THERAPIES HAVE BEEN DEVELOPED

323
00:12:55,798 --> 00:12:56,265
SINCE.

324
00:12:56,265 --> 00:12:57,800
THAT INCLUDES THE THERAPIES

325
00:12:57,800 --> 00:12:58,768
SOLICITED HERE BUT MUCH MORE

326
00:12:58,768 --> 00:13:01,237
THAN THAT, AND THE GENOMIC

327
00:13:01,237 --> 00:13:04,407
HETEROGENEITY IN OUR DECS

328
00:13:04,407 --> 00:13:06,542
CHALLENGING IN EMERGING ITS OF

329
00:13:06,542 --> 00:13:09,378
TARGETING SPECIFIC PATHWAYS

330
00:13:09,378 --> 00:13:10,079
BECAUSE IT'S HETEROGENIUS BUT WE

331
00:13:10,079 --> 00:13:15,184
HAVE BEEN ABLE TO AS I MENTIONED

332
00:13:15,184 --> 00:13:17,353
IDENTIFY COMMON PATH BAYS

333
00:13:17,353 --> 00:13:19,455
WHETHER IT BE TCR, JACK STAT,

334
00:13:19,455 --> 00:13:20,389
SURVIVAL PATHS THAT ARE COMMON

335
00:13:20,389 --> 00:13:22,591
THAT COULD BE TARGETED NOW WITH

336
00:13:22,591 --> 00:13:23,993
THE BETTER MOLECULAR TOOLS AND

337
00:13:23,993 --> 00:13:25,127
THIS IS VERY IMPORTANT

338
00:13:25,127 --> 00:13:26,495
ESPECIALLY IN THE REFRACTORY

339
00:13:26,495 --> 00:13:29,732
SETTING THAT I WILL DESCRIBE

340
00:13:29,732 --> 00:13:30,499
LATER.

341
00:13:30,499 --> 00:13:34,537
AND OBVIOUSLY IMPROVING THE HOST

342
00:13:34,537 --> 00:13:36,238
IMMUNE SYSTEM TO FIGHT, TO

343
00:13:36,238 --> 00:13:38,507
IMPROVE THE ANTITUMOR ACTIVITY,

344
00:13:38,507 --> 00:13:40,943
INCLUDING CHECK POINT INHIBITORS

345
00:13:40,943 --> 00:13:42,878
HAVE BEEN DEVELOPED AND IS VERY

346
00:13:42,878 --> 00:13:45,281
IMPORTANT TO INTEGRATE INTO OUR

347
00:13:45,281 --> 00:13:46,015
TREATMENT ALGORITHM, OBVIOUSLY

348
00:13:46,015 --> 00:13:50,019
WE NEED TO WORRY ABOUT POTENTIAL

349
00:13:50,019 --> 00:13:52,388
HYPEY PROGRESSION IN T-CELL

350
00:13:52,388 --> 00:13:54,056
LYMPHOMA WITH CHECK POINT

351
00:13:54,056 --> 00:13:56,425
INHIBITORS BUT WITH APPROPRIATE

352
00:13:56,425 --> 00:13:57,994
PATIENT SELECTION AND BIOMARKERS

353
00:13:57,994 --> 00:14:01,197
THAT CAN HELP GUIDE, WE HOPE TO

354
00:14:01,197 --> 00:14:05,101
UTILIZE THESE VERY WELL. 

355
00:14:05,101 --> 00:14:07,303
AND IN CTCL, IN MOST CASES NOT A

356
00:14:07,303 --> 00:14:08,571
SINGLE THERAPY IS THE HOME RUN,

357
00:14:08,571 --> 00:14:15,144
BUT WE NEED TO COMBINE

358
00:14:15,144 --> 00:14:17,847
TREATMENTS WITH SKIN DIRECTED OR

359
00:14:17,847 --> 00:14:18,581
SYSTEMIC COMBINATIONS TO

360
00:14:18,581 --> 00:14:20,049
OPTIMIZE TREATMENT.

361
00:14:20,049 --> 00:14:21,751
TO DEMONSTRATE HOW IN REAL LIFE

362
00:14:21,751 --> 00:14:23,452
WE CAN UTILIZE THESE THERAPIES,

363
00:14:23,452 --> 00:14:27,423
BECAUSE IN REAL LIFE CLINICAL

364
00:14:27,423 --> 00:14:29,325
MANAGEMENTS VERY CHALLENGING,

365
00:14:29,325 --> 00:14:30,326
AGAIN BECAUSE OF THE

366
00:14:30,326 --> 00:14:31,093
HETEROGENEITY.

367
00:14:31,093 --> 00:14:32,828
I WILL USE 2 SPECTRUM OF PATIENT

368
00:14:32,828 --> 00:14:34,130
THAT COMMONLY PRESENTED IN OUR

369
00:14:34,130 --> 00:14:35,264
CLIPPIC TO DEMON TRAIT THIS, SO

370
00:14:35,264 --> 00:14:41,704
IN THE LEFT, WE HAVE A PATIENT

371
00:14:41,704 --> 00:14:45,541
WITH MF TUMOR CELL  DISEASE THAT

372
00:14:45,541 --> 00:14:48,077
IS A LARGE TRANSFORMATION THAT

373
00:14:48,077 --> 00:14:49,278
CAN RESPENT TO YOU IN THE CLINIC

374
00:14:49,278 --> 00:14:55,051
AND ON THE RIGHT IS LCT, THAT

375
00:14:55,051 --> 00:14:57,153
CAN PRESENT, AND WHEN HAVE YOU

376
00:14:57,153 --> 00:14:58,387
NOT MANAGED A LOT OF PATIENTS

377
00:14:58,387 --> 00:15:00,022
YOU TRY TO LOOK FOR GUIDE LINE

378
00:15:00,022 --> 00:15:03,292
AND YOU GO TO THE NCCN GUIDELINE

379
00:15:03,292 --> 00:15:05,728
AND IN THE GUIDELINE YOU HAVE A

380
00:15:05,728 --> 00:15:08,664
LISTING MENU OF TREATMENT

381
00:15:08,664 --> 00:15:09,965
OPTIONS, AND THAT 1 SINGLE FRONT

382
00:15:09,965 --> 00:15:11,400
LINE REGIMEN THAT YOU CAN START

383
00:15:11,400 --> 00:15:14,103
WITH, THIS KIND OF TELLS YOU

384
00:15:14,103 --> 00:15:17,139
THAT THERE'S NO

385
00:15:17,139 --> 00:15:18,040
ONE-SIZE-FITS-ALL FRONT LINE

386
00:15:18,040 --> 00:15:22,211
CHOICE AND YOU HAVE TO REALLY

387
00:15:22,211 --> 00:15:23,946
PERSONALIZE TO MATCH THE PATIENT

388
00:15:23,946 --> 00:15:28,751
PROFILE IN THIS VERY DIVERSE

389
00:15:28,751 --> 00:15:29,085
DISEASE GROUP.

390
00:15:29,085 --> 00:15:31,454
THAT KIND OF LEADS YOU TO, WELL,

391
00:15:31,454 --> 00:15:32,822
THEN IN WITH ALL THE TREMES THAT

392
00:15:32,822 --> 00:15:34,323
ARE IN THE LISTING FASHION AND

393
00:15:34,323 --> 00:15:37,159
THE PATIENT PROFILE THAT'S VERY

394
00:15:37,159 --> 00:15:38,661
HETEROGENIUS, WHAT HAPPENS YOU

395
00:15:38,661 --> 00:15:41,063
DECIDE IN PICKING THE RIGHT

396
00:15:41,063 --> 00:15:41,330
TREATMENT?

397
00:15:41,330 --> 00:15:42,765
SO WE HAVE SPENT TIME IN TRYING

398
00:15:42,765 --> 00:15:45,668
TO GIVE A FRAMEWORK OF

399
00:15:45,668 --> 00:15:48,537
MANAGEMENT, FOR OUR CLINICAL

400
00:15:48,537 --> 00:15:52,641
CARE PROVIDERS, SO, IN OUR

401
00:15:52,641 --> 00:16:01,317
DISEASE, WHEN THERE'S SKIN,

402
00:16:01,317 --> 00:16:02,985
BLOOD, AND VISA AND THAT COULD

403
00:16:02,985 --> 00:16:05,221
BE A DYNAMIC PROCESS SO YOU NEED

404
00:16:05,221 --> 00:16:08,090
TO UPDATE THAT WITH PATES CHANGE

405
00:16:08,090 --> 00:16:10,126
IN THERAPY AND YOU NEED TO

406
00:16:10,126 --> 00:16:11,627
CHARACTERIZE THE COMPARTMENTAL

407
00:16:11,627 --> 00:16:13,762
DISEASE, AND THE BURDEN, AND

408
00:16:13,762 --> 00:16:16,298
THEN YOU HAVE OTHER FACTORS TO

409
00:16:16,298 --> 00:16:17,766
CONSIDER INCLUDING LARGE CELL

410
00:16:17,766 --> 00:16:19,602
TRANSFORMATION THAT I ALLUDED

411
00:16:19,602 --> 00:16:23,305
TO, POTENTIAL ACTIONABLE TARGETS

412
00:16:23,305 --> 00:16:24,507
WHICH ALSO CAN CHANGE OVER TIME

413
00:16:24,507 --> 00:16:26,142
SO THOSE HAVE TO BE

414
00:16:26,142 --> 00:16:30,212
CHARACTERIZED AND IMPOSSIBLE TO

415
00:16:30,212 --> 00:16:32,081
BUILD GREATED AND TO HIGHLIGHT

416
00:16:32,081 --> 00:16:34,216
HOW WE MIGHT UTILIZE THESE KIND

417
00:16:34,216 --> 00:16:35,117
OF INFORMATION, I HAVE THIS

418
00:16:35,117 --> 00:16:36,552
DIAGRAM ON THE RIGHT WHICH IS AN

419
00:16:36,552 --> 00:16:38,921
EXAMPLE OF THE KEY TREATMENTS

420
00:16:38,921 --> 00:16:42,124
THAT WE WILL USE IN CTCL, AND

421
00:16:42,124 --> 00:16:45,961
THE COLOR CODE IS THAT GREEN IS

422
00:16:45,961 --> 00:16:47,429
WHERE THERE'S EVIDENT, CARCKER

423
00:16:47,429 --> 00:16:49,098
GREEN BEING MORE EVIDENT, AND

424
00:16:49,098 --> 00:16:51,867
THE LIGHTER GREEN, AND THE RED

425
00:16:51,867 --> 00:16:52,902
DENOTES, WHERE WE HAVE LESS

426
00:16:52,902 --> 00:16:57,640
EVIDENT OR LACK OF ACTIVITY IN

427
00:16:57,640 --> 00:16:58,841
THAT DISEASE PROFILE.

428
00:16:58,841 --> 00:17:00,876
FOR EXAMPLE, PATIENTS WITH

429
00:17:00,876 --> 00:17:03,546
THICKER SKIN DISEASE WITH

430
00:17:03,546 --> 00:17:07,750
TRIMMER NODULES, THICK SKIN AND

431
00:17:07,750 --> 00:17:08,317
TRANSFORMATION GEOGAFFIC DEC

432
00:17:08,317 --> 00:17:18,794
PROFILE, THE DATA SHOWS THAT

433
00:17:19,028 --> 00:17:23,766
BRENTUXIMAB, WHICH I WILL SPEAK

434
00:17:23,766 --> 00:17:29,138
ABOUT LATER ON, WHEREAS

435
00:17:29,138 --> 00:17:30,306
ROMIDEPSIN, AND WORKS BETTER

436
00:17:30,306 --> 00:17:31,774
WITH SKIN INVOLVEMENT BUT DOES

437
00:17:31,774 --> 00:17:34,343
NOT ALIEP WELL WITH THE

438
00:17:34,343 --> 00:17:35,511
TRANSFORMED THICKER SKIN DISEASE

439
00:17:35,511 --> 00:17:46,021
PATES WHEREAS THE OTHER TREMES

440
00:17:46,555 --> 00:17:49,558
LIKE PRALATEXATE, AND CAN HELP

441
00:17:49,558 --> 00:17:50,559
WITH OTHER SKIN TYPES BUT THE

442
00:17:50,559 --> 00:17:53,329
DAILY BASIS THEA IS MUCH LESS

443
00:17:53,329 --> 00:17:55,030
ROBUST, AND WE MAY NOT USE THEM

444
00:17:55,030 --> 00:17:56,432
UPFRONT IN THAT DISEASE, BUT

445
00:17:56,432 --> 00:17:58,968
THEY ARE GREAT CHOICES TO HAVE.

446
00:17:58,968 --> 00:18:01,737
TO DEMON TRAIT THIS FURTHER WE

447
00:18:01,737 --> 00:18:03,239
WILL USE OUR PATIENT AS AN

448
00:18:03,239 --> 00:18:04,506
EXAMPLE, AND KEEPING THAT

449
00:18:04,506 --> 00:18:07,810
FRAMEWORK IN MIND, WE WILL GO

450
00:18:07,810 --> 00:18:09,511
THROUGH THE PATIENT'S PATH.

451
00:18:09,511 --> 00:18:14,416
SO THIS PEASHT IS AN ERYTH ROUGH

452
00:18:14,416 --> 00:18:15,799
ATOM DERMIC PATIENT WITH, SO

453
00:18:15,799 --> 00:18:18,569
SKIN ELITHE ROUGH ATOM DERMA, NO

454
00:18:18,569 --> 00:18:20,003
LYMPHNODE DISEASE AND NO

455
00:18:20,003 --> 00:18:22,573
VISCERAL DISEASE.

456
00:18:22,573 --> 00:18:23,941
SO WHAT ALIGNS WELL WITH THAT

457
00:18:23,941 --> 00:18:33,484
KIND OF PEASHT PROFILE AGAIN IS

458
00:18:33,484 --> 00:18:35,552
THIS MOBAMAZAB, AND IT WAS A

459
00:18:35,552 --> 00:18:36,520
RANDOMIZED CONTROL TRIAL, HAS

460
00:18:36,520 --> 00:18:37,521
GREAT ACTIVITY IN THE BLOOD

461
00:18:37,521 --> 00:18:39,723
COMPART AM AS YOU CAN SEE,

462
00:18:39,723 --> 00:18:42,693
COMPARED TO OTHER DRUGS, HIGH

463
00:18:42,693 --> 00:18:43,761
AMOUNT, HIGH PERCENTAGE OF

464
00:18:43,761 --> 00:18:51,435
COMPLETE RESPONSES IN THE BLOOD

465
00:18:51,435 --> 00:18:52,269
THAT'S HIGHLY DURABLE SO IF YOU

466
00:18:52,269 --> 00:18:54,705
HAVE A PATIENT LIKE HOURS WITH

467
00:18:54,705 --> 00:19:00,144
HIGH BLOOD DERMA, SELECTING

468
00:19:00,144 --> 00:19:04,515
MOIMRKS AMULIZUMAB WOULD BE A

469
00:19:04,515 --> 00:19:07,785
GOOD  CHOICE IN THIS PATIENT.

470
00:19:07,785 --> 00:19:18,128
I WANT TO EXPAND ON HOW

471
00:19:18,128 --> 00:19:22,266
MOGAMULIZUMAB HAS BEEN APPROVED

472
00:19:22,266 --> 00:19:26,436
IN PTCL, AND CTCL AND BECAUSE

473
00:19:26,436 --> 00:19:28,172
NOT ONLY IS IT OVEREXPRESSED IN

474
00:19:28,172 --> 00:19:31,208
THE CELLS, IN JAPAN IT WAS

475
00:19:31,208 --> 00:19:32,910
APPROVE INDEED ATL AND THEN WE

476
00:19:32,910 --> 00:19:35,145
BORROWED IT TO ADVANCE IN CTCL

477
00:19:35,145 --> 00:19:37,080
AS WELL, BECAUSE THE TARGET IS

478
00:19:37,080 --> 00:19:37,815
VERY RELEVANT.

479
00:19:37,815 --> 00:19:39,082
NOT ONLY IS IT HIGHLY EXPRESSED

480
00:19:39,082 --> 00:19:43,153
IN THE TUMOR BUT KRRK CL 4 IS

481
00:19:43,153 --> 00:19:44,121
HIGHLY EXPRESSED IN TREGULATORY

482
00:19:44,121 --> 00:19:46,890
CELLS AND IT HAS A DUAL

483
00:19:46,890 --> 00:19:48,959
EFFECTIVE IMMUNE AUGMENTATION BY

484
00:19:48,959 --> 00:19:52,396
DEPLETING TREGS WHICH MAY HAVE A

485
00:19:52,396 --> 00:19:53,463
NEGATIVE INHIBITORY EFFECT FOR

486
00:19:53,463 --> 00:19:56,900
YOUR IMMUNE SYSTEM AS WELL AS

487
00:19:56,900 --> 00:19:58,602
DIRECTLY TARGETING THE TUMOR

488
00:19:58,602 --> 00:19:58,802
CELLS.

489
00:19:58,802 --> 00:20:06,844
SO AGAIN, WANTED TO USE

490
00:20:06,844 --> 00:20:08,111
MOGAMULIZUMAB AS AN EXAMPLE, AND

491
00:20:08,111 --> 00:20:10,180
HOW WE LEARN ABOUT THE

492
00:20:10,180 --> 00:20:10,747
RESISTANCE MECHANISMS WHICH

493
00:20:10,747 --> 00:20:12,216
WOULD LEAD TO UNDERSTANDING HOW

494
00:20:12,216 --> 00:20:14,084
WE CAN COMBINE OUR SEQUENCE

495
00:20:14,084 --> 00:20:15,752
DRUGS BETTER.

496
00:20:15,752 --> 00:20:17,020
SO AGAIN, MOGAMULIZUMAB WAS

497
00:20:17,020 --> 00:20:20,190
APPROVED, IT WAS APPROVED IN

498
00:20:20,190 --> 00:20:21,758
2018 AND THE TRIAL THAT LED TO

499
00:20:21,758 --> 00:20:24,761
THE APPROVAL WAS CALLED

500
00:20:24,761 --> 00:20:25,762
MAVERICK, WHICH EXCLUDED

501
00:20:25,762 --> 00:20:27,898
ACTUALLY LARGE CELL

502
00:20:27,898 --> 00:20:28,298
TRANSFORMATION.

503
00:20:28,298 --> 00:20:31,768
OF PATIENTS BECAUSE, IN THE

504
00:20:31,768 --> 00:20:32,236
EARLIER PHASE TRIALS,

505
00:20:32,236 --> 00:20:33,337
MOGAMULIZUMAB DID NOT HAVE GOOD

506
00:20:33,337 --> 00:20:35,639
ACTIVITY IN THE AGGRESSIVE LCT,

507
00:20:35,639 --> 00:20:38,475
BUT HAD MORE ACTIVITY IN THE

508
00:20:38,475 --> 00:20:39,843
LEUKEMIC DISEASE, AND THE

509
00:20:39,843 --> 00:20:41,511
PIVOTAL TRIAL DID CONFIRM THAT

510
00:20:41,511 --> 00:20:43,580
IT HAS MORE ACTIVITY IN THE

511
00:20:43,580 --> 00:20:45,015
SENSORY SEN ILLEGALSEN DROAM

512
00:20:45,015 --> 00:20:47,718
WHICH IS A LEUKEMIC PROFILE AND

513
00:20:47,718 --> 00:20:50,053
GREAT ACTIVITY IN THE BLOOD

514
00:20:50,053 --> 00:20:51,555
COMPARTMENT, VERY RAPID RESPONSE

515
00:20:51,555 --> 00:20:52,789
THAT'S VERY DURABLE, IF THEY

516
00:20:52,789 --> 00:20:54,691
DIDN'T HAVE AS GREAT ACTIVITY IN

517
00:20:54,691 --> 00:20:56,793
THE THICKER TUMOR DISEASE, NOR

518
00:20:56,793 --> 00:20:59,796
IN THE LYMPHNODES SO CLEARLY

519
00:20:59,796 --> 00:21:02,933
PROOF THAT LEUKEMIC DISEASE WAS

520
00:21:02,933 --> 00:21:04,668
A BETTER MATCH FOR

521
00:21:04,668 --> 00:21:05,269
MOGAMULIZUMAB.

522
00:21:05,269 --> 00:21:07,871
AND IT TURNS OUT THAT THE

523
00:21:07,871 --> 00:21:08,839
LONG-TERM RESPONDERS THAT

524
00:21:08,839 --> 00:21:11,241
BENEFIT MORE THAN 12 MONTHS,

525
00:21:11,241 --> 00:21:13,443
DURABLE RESPONSE FOR 12 MONTHS,

526
00:21:13,443 --> 00:21:16,146
MOST OF THEM ARE SYNDROME

527
00:21:16,146 --> 00:21:16,513
PATIENTS.

528
00:21:16,513 --> 00:21:20,083
SO AGAIN, IF YOU HAVE A SENSORY

529
00:21:20,083 --> 00:21:22,119
PATIENT, THICKER DISEASE, THAT

530
00:21:22,119 --> 00:21:23,387
WOULD MATCH WITH THIS DRUG.

531
00:21:23,387 --> 00:21:24,521
OF THE SIDE CENTER FOR

532
00:21:24,521 --> 00:21:31,094
EXCELLENCE ON AGINGS OF

533
00:21:31,094 --> 00:21:32,396
MOGAMULIZUMAB, IT'S VERY

534
00:21:32,396 --> 00:21:32,996
IMPORTANT FROM THE TOXICITIES

535
00:21:32,996 --> 00:21:34,698
BECAUSE IT COULD BE A CLUE AS TO

536
00:21:34,698 --> 00:21:38,735
WHETHER IT'S A GOOD MARKER AS

537
00:21:38,735 --> 00:21:39,069
WELL.

538
00:21:39,069 --> 00:21:43,473
SO MAR HAS BEEN SEEN VERY UNIQUE

539
00:21:43,473 --> 00:21:44,675
TO THIS DRUG, AND IT'S

540
00:21:44,675 --> 00:21:46,109
NOVEMBER-IN THE TRIAL IT WAS

541
00:21:46,109 --> 00:21:48,245
ABOUT INCIDENCE WAS ABOUT 25%

542
00:21:48,245 --> 00:21:50,280
BUT IN THE REAL WORLD

543
00:21:50,280 --> 00:21:53,617
EXPERIENCE, THE RASH IS MUCH

544
00:21:53,617 --> 00:21:55,752
MORE PROBLEMATIC, MUCH HIGHER IN

545
00:21:55,752 --> 00:21:57,688
INCIDENCE, AND WE NEEDED TO

546
00:21:57,688 --> 00:21:59,222
LEARN A LITTLE BIT MORE ABOUT

547
00:21:59,222 --> 00:22:02,092
THE RASH BECAUSE IN A CTCL

548
00:22:02,092 --> 00:22:03,427
PATIENT WITH CUTANEOUS DISEASE,

549
00:22:03,427 --> 00:22:06,330
WHEN YOU GET A RASH, IT COULD BE

550
00:22:06,330 --> 00:22:07,798
VERY CHALLENGING, IS IT A RASH?

551
00:22:07,798 --> 00:22:10,300
OR IS IT THE DISEASE

552
00:22:10,300 --> 00:22:10,867
PROGRESSING, GETTING WORSE?

553
00:22:10,867 --> 00:22:14,471
AND YOU CAN SEE ON THE RIGHT,

554
00:22:14,471 --> 00:22:17,274
THE RASH COULD BE VERY

555
00:22:17,274 --> 00:22:19,977
HETEROGENIUS AND PHOTO

556
00:22:19,977 --> 00:22:22,546
SENSITIVE, OR IT COULD BE TUMOR

557
00:22:22,546 --> 00:22:25,115
NODULAR TYPE OF LESIONS BUT IT'S

558
00:22:25,115 --> 00:22:27,951
NOT COMPOSED OF CTCL CELLS BUT

559
00:22:27,951 --> 00:22:30,120
MORE EFTHIMIOSIO SIDIC AND OTHER

560
00:22:30,120 --> 00:22:31,221
REACTIVE INFILTRATE BUT IT LOOKS

561
00:22:31,221 --> 00:22:35,659
LIKE IT COULD BE LYMPHOMA, THUS

562
00:22:35,659 --> 00:22:38,695
WE NEED TO BIOPSY WHEN WE ARE

563
00:22:38,695 --> 00:22:40,030
SUSPECTING IT, KNOWING THE

564
00:22:40,030 --> 00:22:41,898
CLONALITY OF THE DISEASE AND

565
00:22:41,898 --> 00:22:43,834
IMMUNO PHENOTYPE OF THE ORIGINAL

566
00:22:43,834 --> 00:22:46,336
DISEASE HELPS US DISTINGUISH THE

567
00:22:46,336 --> 00:22:47,104
RASH.

568
00:22:47,104 --> 00:22:48,872
THE RASH IS HIGHLY MANAGEABLE,

569
00:22:48,872 --> 00:22:50,707
AND IT DEPENDS ON THE SEVERITY

570
00:22:50,707 --> 00:22:52,442
OF THE RASH, WHERE WE USE MILD

571
00:22:52,442 --> 00:22:54,378
TREATMENT, WHERE WE HAVE TO STOP

572
00:22:54,378 --> 00:22:55,979
THE DRUG AND DO MORE, BUT IT

573
00:22:55,979 --> 00:22:58,315
TURNS OUT, YOU MAY ASK, IS THIS

574
00:22:58,315 --> 00:22:59,950
RASH, A GOOD THING OR A BAD

575
00:22:59,950 --> 00:23:06,023
THING FOR THE PATIENTS IT TURNS

576
00:23:06,023 --> 00:23:07,524
OUT THAT THE MORE WITH PATIENT

577
00:23:07,524 --> 00:23:09,226
WHO IS DO BETTER, SO YOU CAN

578
00:23:09,226 --> 00:23:11,628
TELL IN SENSORY PATIENT, WE SELL

579
00:23:11,628 --> 00:23:18,535
MORE OF THE MAR AND IT'S

580
00:23:18,535 --> 00:23:19,336
PROBABLY A REFLECTION THAT

581
00:23:19,336 --> 00:23:20,404
MOGAMULIZUMAB WHICH IS AN IMMUNE

582
00:23:20,404 --> 00:23:21,138
THERAPY AND ACTIVITIES AND

583
00:23:21,138 --> 00:23:23,273
PROJECTS THAT'S DEPENDS ON

584
00:23:23,273 --> 00:23:24,808
ADCC MAY BE IMPEDIMENTSUNE

585
00:23:24,808 --> 00:23:26,343
ACTIVITIES MORE ROBUST IN THOSE

586
00:23:26,343 --> 00:23:28,545
PATIENTS WITH MAR, AND CLEARLY

587
00:23:28,545 --> 00:23:34,751
IN THE STUDY WE DID AT STANFORD,

588
00:23:34,751 --> 00:23:38,121
WITH MOGAMULIZUMAB, WE LOOKED AT

589
00:23:38,121 --> 00:23:40,624
RESPONDERS TO MOGAMULIZUMAB AND

590
00:23:40,624 --> 00:23:42,459
NONRESPONDERS, RED FOR THOSE

591
00:23:42,459 --> 00:23:44,494
WITH MAR POSITIVE AND BLUE DOTS

592
00:23:44,494 --> 00:23:46,263
ARE THOSE WITHOUT MAR, YOU CAN

593
00:23:46,263 --> 00:23:49,166
SEE THAT PATIENTS LO LOCATED AND

594
00:23:49,166 --> 00:23:50,434
ENRICHED IN THE RESPONDERS, KIND

595
00:23:50,434 --> 00:23:54,471
OF SAYING THAT WELL, AGAIN, IT'S

596
00:23:54,471 --> 00:23:56,306
A PASSIVE THING THAT WE SEE WITH

597
00:23:56,306 --> 00:23:58,442
THE RESPONDERS OR IS THAT A

598
00:23:58,442 --> 00:24:01,945
REFLECTION OF GOOD  IMMUNE

599
00:24:01,945 --> 00:24:03,280
ACTIVITY IN THAT IS DETERMINED

600
00:24:03,280 --> 00:24:04,481
BUT CLEARLY WHEN YOU HAVE A

601
00:24:04,481 --> 00:24:06,249
PATIENT WITH THIS BAD RASH, NOT

602
00:24:06,249 --> 00:24:08,985
ONLY DOES IT GO WITH MORE

603
00:24:08,985 --> 00:24:11,188
RESPONSE, BUT ALSO, THE DURATION

604
00:24:11,188 --> 00:24:13,457
OF RESPONSE IN OUR TIME TO NEXT

605
00:24:13,457 --> 00:24:14,658
TREATMENT, AND PFS, THE PATIENTS

606
00:24:14,658 --> 00:24:17,260
WITH RED LINE WHICH IS THE MAR

607
00:24:17,260 --> 00:24:19,629
PATIENTS, HAVE MUCH MORE

608
00:24:19,629 --> 00:24:21,565
BENEFIT, SO YOU MAY BE A GOOD

609
00:24:21,565 --> 00:24:23,033
THING, WE CAN REASSURE THE

610
00:24:23,033 --> 00:24:24,968
PATIENTS THAT ALTHOUGH IT'S A

611
00:24:24,968 --> 00:24:26,336
VERY ANNOYING TYPE OF SIDE

612
00:24:26,336 --> 00:24:30,440
EFFECT, THAT IT MAY BE A GOOD

613
00:24:30,440 --> 00:24:32,576
FACTOR, A GOOD RESPONSE MARKER,

614
00:24:32,576 --> 00:24:33,743
HOWEVER THOSE WITHOUT MAR CAN

615
00:24:33,743 --> 00:24:36,046
ALSO HAVE GOOD RESPONSE, SO WE

616
00:24:36,046 --> 00:24:37,781
STILL NEED TO UNDERSTAND MORE

617
00:24:37,781 --> 00:24:39,749
AND MAYBE ONCE WE UNDERSTAND

618
00:24:39,749 --> 00:24:41,284
THAT, WE CAN AUGMENT THOSE

619
00:24:41,284 --> 00:24:45,822
FACTORS TO IMPROVE THE DRUG

620
00:24:45,822 --> 00:24:46,389
ACTIVITY.

621
00:24:46,389 --> 00:24:48,658
AS I MENTIONED THIS DRUG IS

622
00:24:48,658 --> 00:24:49,926
HIGHLY ACTIVE IN LEUKEMIC

623
00:24:49,926 --> 00:24:53,330
DISEASE AND NOT AS ACTIVE IN THE

624
00:24:53,330 --> 00:24:54,631
THICKER DISEASE IN THE SKIN OR

625
00:24:54,631 --> 00:24:57,534
LYMPHNODE OR IN THE TRANSFORM

626
00:24:57,534 --> 00:24:59,336
AGGRESSIVE DISEASE.

627
00:24:59,336 --> 00:25:00,604
SO ONCE THIS--WE WANT TO

628
00:25:00,604 --> 00:25:04,040
LEVERAGE OFF OF ITS POWER, THE

629
00:25:04,040 --> 00:25:05,909
GOOD ACTIVITY AND IN PATIENTS

630
00:25:05,909 --> 00:25:08,245
WITH THICKER DISEASE, WITH

631
00:25:08,245 --> 00:25:10,180
LEUKEMIC INVOLVEMENT, HOW CAN WE

632
00:25:10,180 --> 00:25:15,218
COMBINE TREATMENTS TO OPTIMIZE

633
00:25:15,218 --> 00:25:16,086
AND MAXIMIZE UTILITY OF

634
00:25:16,086 --> 00:25:22,058
MOGAMULIZUMAB, SO THAT LEADS TO

635
00:25:22,058 --> 00:25:23,627
MAXIMIZING EFFICACY WITH

636
00:25:23,627 --> 00:25:24,961
ACCEPTABLE TOXICITIES, FOR

637
00:25:24,961 --> 00:25:25,695
EXAMPLE, WE CAN COMBINE THAT

638
00:25:25,695 --> 00:25:27,697
WITH A TREATMENT THAT REALLY

639
00:25:27,697 --> 00:25:29,166
BEBUNKS THE SKIN DEC WELL WHICH

640
00:25:29,166 --> 00:25:31,134
IS THE RADIATION, SO WE HAVE A

641
00:25:31,134 --> 00:25:32,836
TRIAL AT STANFORD AND A TRIAL

642
00:25:32,836 --> 00:25:34,738
THIS BY THE EUROPEAN COLLEAGUES

643
00:25:34,738 --> 00:25:36,306
THAT WOULD COMBINE THE ACTIVITY

644
00:25:36,306 --> 00:25:40,143
OF THE TOTAL SKIN IN

645
00:25:40,143 --> 00:25:40,844
MOGAMULIZUMAB GETTING AT THE

646
00:25:40,844 --> 00:25:44,114
BEST OF BOTH SIDES OF ACTIVITY

647
00:25:44,114 --> 00:25:47,918
AND COMBOYNING BOYNING--COMBINI.

648
00:25:47,918 --> 00:25:49,419
AND THEN ALSO SUSTAINED THE

649
00:25:49,419 --> 00:25:50,520
DISEASE RESPONSE, AND THEN WE

650
00:25:50,520 --> 00:25:54,291
HAVE OTHER DRUGS THAT CAN BE

651
00:25:54,291 --> 00:25:55,158
COMBINED, WITH MOGAMULIZUMAB,

652
00:25:55,158 --> 00:25:58,495
THAT COULD IMPROVE THE

653
00:25:58,495 --> 00:25:59,663
COMBINATION ACTIVITY, ALSO THAT

654
00:25:59,663 --> 00:26:03,567
WE CAN LOOK AT IMMUNE SYNERGY OF

655
00:26:03,567 --> 00:26:06,636
AUGMENTATION WITH ACTIVITY, AND

656
00:26:06,636 --> 00:26:10,340
THAT INCLUDES COMBINING WITH

657
00:26:10,340 --> 00:26:13,043
ANTICD47, WHICH HAS BEEN SHOWN

658
00:26:13,043 --> 00:26:15,145
TO HAVE HAD GREAT ACTIVITY, AND

659
00:26:15,145 --> 00:26:18,548
WE'RE USING PATIENT CELL LINES

660
00:26:18,548 --> 00:26:19,583
AND THERE'S A CLINICAL TRIAL

661
00:26:19,583 --> 00:26:22,352
THAT WAS DEVELOPED TO COMBINE

662
00:26:22,352 --> 00:26:23,887
THE 2 DRUGS, AND UNFORTUNATELY

663
00:26:23,887 --> 00:26:28,258
WE WERE JUST TOLD THAT UTILITY

664
00:26:28,258 --> 00:26:31,094
AND HEMEAT O LOGIC MALIGNANCY IS

665
00:26:31,094 --> 00:26:32,896
HAS BEEN HALTED SO UNFORTUNATELY

666
00:26:32,896 --> 00:26:34,764
DUE TO SOME SIDE EFFECTS IN THE

667
00:26:34,764 --> 00:26:38,068
AML PATIENTS, BUT IT WAS A

668
00:26:38,068 --> 00:26:39,736
VERY--POTENTIALLY A VERY GOOD

669
00:26:39,736 --> 00:26:41,972
COMBINATION OF SINNER GESTIC

670
00:26:41,972 --> 00:26:43,807
ACTIVITY JUST TO SHOW WE CAN

671
00:26:43,807 --> 00:26:45,308
ENHANCE ACTIVITY BY FINDING OUT

672
00:26:45,308 --> 00:26:47,077
WHICH DRUGS HAVE SYNERGY AND

673
00:26:47,077 --> 00:26:48,445
THERE ARE MANY OTHER TRIALS

674
00:26:48,445 --> 00:26:50,947
INCLUDING TRIAL AT THE NIH THAT

675
00:26:50,947 --> 00:26:52,983
COULD LEVERAGE OFF ACTIVITY OF

676
00:26:52,983 --> 00:26:55,452
MOGAMULIZUMAB AND TO ALSO

677
00:26:55,452 --> 00:26:56,886
COMBINE WITH OTHER AGENTS.

678
00:26:56,886 --> 00:27:00,090
ONE MAY ASK WHAT DO WE KNOW

679
00:27:00,090 --> 00:27:00,490
ABOUT THE TARGET?

680
00:27:00,490 --> 00:27:03,426
SO THE DRUG TARGETS CCR4, SO

681
00:27:03,426 --> 00:27:09,232
DOES IT DO BETTER IN THOSE WITH

682
00:27:09,232 --> 00:27:10,600
HIGHER CCR4 EXPRESSION?

683
00:27:10,600 --> 00:27:13,303
IN CTCL, THE CCL IS CONSISTENTLY

684
00:27:13,303 --> 00:27:16,606
HIGHLY EXPRESSED BECAUSE IT IS A

685
00:27:16,606 --> 00:27:18,508
CHEMO KEEN THAT TRAFFICS THE

686
00:27:18,508 --> 00:27:21,144
LYMPHOCYTES TO THE SKIN THUS

687
00:27:21,144 --> 00:27:23,446
GUYS THE CTCL CELLS TO THE SKIN.

688
00:27:23,446 --> 00:27:24,948
SO THE MEDIAN EXPRESSION IN THE

689
00:27:24,948 --> 00:27:27,083
SKIN OF CCL IS VERY HIGH.

690
00:27:27,083 --> 00:27:29,853
IT'S IN THE 27%.

691
00:27:29,853 --> 00:27:31,855
SO THE PRESENCE IN THE HIGHER

692
00:27:31,855 --> 00:27:34,557
LEVEL, DOES NOT REALLY CORRELATE

693
00:27:34,557 --> 00:27:36,926
AS EXPECTED, BUT THERE ARE SOME

694
00:27:36,926 --> 00:27:39,296
PATIENTS WITH VERY LOW LEVEL OF

695
00:27:39,296 --> 00:27:41,598
EXPRESSION THAT DID NOT LOCALIZE

696
00:27:41,598 --> 00:27:44,401
WITH THE RESPONDERS, SO YOU

697
00:27:44,401 --> 00:27:46,069
WONDER IF VERY NEGATIVE

698
00:27:46,069 --> 00:27:47,037
EXPRESSION OF CCR 4 COULD BE A

699
00:27:47,037 --> 00:27:48,872
PATIENT YOU DON'T WANT TO GIVE

700
00:27:48,872 --> 00:27:52,909
THE DRUG, BUT AGAIN THIS IS TO

701
00:27:52,909 --> 00:27:54,444
BE DETERMINED FURTHER AND BUT

702
00:27:54,444 --> 00:28:01,251
IT'S AN INTERESTING OBSERVATION 

703
00:28:01,251 --> 00:28:05,889
YOU MAY ALSO ASK HOW MANY

704
00:28:05,889 --> 00:28:07,691
TARGETS IN THE GENE, AND THERE'S

705
00:28:07,691 --> 00:28:09,693
EVIDENCE IN THE ATL LITERATURE

706
00:28:09,693 --> 00:28:11,594
IF YOU HAVE A GAIN OF FUNCTION

707
00:28:11,594 --> 00:28:15,598
MUTATION IN THE C-TERMINUS,

708
00:28:15,598 --> 00:28:18,802
REGION OF THE CCR 4 GENE THAT,

709
00:28:18,802 --> 00:28:20,637
IT ENHANCES, THE EXPRESSION OF

710
00:28:20,637 --> 00:28:24,441
CCR 4, AND THAT YOU MAY HAVE

711
00:28:24,441 --> 00:28:26,643
MORE AUGMENTATION OF CLINICAL

712
00:28:26,643 --> 00:28:29,045
ACTIVITY, AND CLEARLY MAINTAIN

713
00:28:29,045 --> 00:28:31,881
HERE THAT'S BEEN SHOWN WITH

714
00:28:31,881 --> 00:28:33,216
MOGAMULIZUMAB, PATIENTS DID

715
00:28:33,216 --> 00:28:36,086
BETTER THAN PATIENTS WITHOUT

716
00:28:36,086 --> 00:28:38,455
MOGAMULIZUMAB WHO REQUIRED

717
00:28:38,455 --> 00:28:38,922
TRANSPLANTS.

718
00:28:38,922 --> 00:28:40,690
SOME MOGAMULIZUMAB PATIENTS DID

719
00:28:40,690 --> 00:28:41,691
BETTER EACH WITHOUT TRANSPLANT

720
00:28:41,691 --> 00:28:45,395
BUT IS THIS THE CASE IN CTCL?

721
00:28:45,395 --> 00:28:48,531
SO YOU WONDER, AND IN CTCL, THE

722
00:28:48,531 --> 00:28:52,202
CCR 4 GAIN OF FUNCTION MUTATION

723
00:28:52,202 --> 00:28:53,670
IS MUCH LESS COMMON AND IN SOME

724
00:28:53,670 --> 00:28:55,372
PATIENTS WITH THE MUTATION, WE

725
00:28:55,372 --> 00:28:57,574
SEE DRAMATIC RESPONSES LIKE

726
00:28:57,574 --> 00:28:57,774
THIS.

727
00:28:57,774 --> 00:28:59,743
SO THIS IS A PATIENT WITH THE

728
00:28:59,743 --> 00:29:01,211
KNOWN GAIN OF FUNCTION, WHO DID

729
00:29:01,211 --> 00:29:04,414
REALLY WELL IN THE BLOOD AND

730
00:29:04,414 --> 00:29:04,981
SKIN.

731
00:29:04,981 --> 00:29:06,583
BUT YOU MAY WONDER THAT THE

732
00:29:06,583 --> 00:29:08,551
PATIENTS MAY DO WELL, WITHOUT

733
00:29:08,551 --> 00:29:11,521
THE MUTATION, TOO, SO, HOW

734
00:29:11,521 --> 00:29:13,356
RELEVANT IS THIS GAIN OF

735
00:29:13,356 --> 00:29:14,958
FUNCTION MUTATION IN THE

736
00:29:14,958 --> 00:29:17,694
PATIENT'S BENEFIT, THAT'S STILL

737
00:29:17,694 --> 00:29:17,961
UNCLEAR.

738
00:29:17,961 --> 00:29:19,596
BUT WE DID SEE THAT PATIENTS

739
00:29:19,596 --> 00:29:20,864
WITH GAIN OF FUNCTION MUTATION,

740
00:29:20,864 --> 00:29:24,601
IF THEY HAVE OTHER NEGATIVE

741
00:29:24,601 --> 00:29:26,269
FACTORS LIKE LARGE CELL

742
00:29:26,269 --> 00:29:27,270
TRANSFORMATION, THEY DID NOT

743
00:29:27,270 --> 00:29:28,438
RESPOND EMPLOY SO OBVIOUSLY IF

744
00:29:28,438 --> 00:29:29,706
YOU HAVE OTHER FACTORS THAT

745
00:29:29,706 --> 00:29:31,074
DRIVE THE AGGRESSIVENESS THAT IT

746
00:29:31,074 --> 00:29:32,242
MAY NOT DO WELL.

747
00:29:32,242 --> 00:29:35,378
WE ALSO THEN LOOKED AT WHAT ARE

748
00:29:35,378 --> 00:29:36,312
THE RESISTANCE MECHANISMS FOR

749
00:29:36,312 --> 00:29:38,581
MOGAMULIZUMAB MOGAMULIZUMAB, AND

750
00:29:38,581 --> 00:29:39,783
IT TURNS OUT THAT WHETHER YOU

751
00:29:39,783 --> 00:29:42,952
LOOK AT THE SECONDARY OR PRIMARY

752
00:29:42,952 --> 00:29:44,954
RESISTANCE PATIENTS WHEN THEY

753
00:29:44,954 --> 00:29:45,889
BECOME RESISTANCE, THE TARGET IN

754
00:29:45,889 --> 00:29:48,191
THE SKIN OR IN THE BLOOD, THE

755
00:29:48,191 --> 00:29:51,528
CCR 4 LEVELS DO GO DOWN.

756
00:29:51,528 --> 00:29:54,330
AND WE'VE SEEN THAT IN 3 OF THE

757
00:29:54,330 --> 00:29:57,734
PATIENTS, ALONG WITH THE CCR 4

758
00:29:57,734 --> 00:29:59,335
EXPRESSION DECREASE, THEY DO

759
00:29:59,335 --> 00:30:01,571
HAVE MOLECULAR NEW MUTATIONS IN

760
00:30:01,571 --> 00:30:03,406
THE CCR 4, INCLUDING THE 1 IN

761
00:30:03,406 --> 00:30:05,041
THE BINDING REGION, THIS IS THE

762
00:30:05,041 --> 00:30:06,810
1 THAT PREDICTS GOOD RESPONSE,

763
00:30:06,810 --> 00:30:10,613
AND IN THE RESISTANCE, WE SEE

764
00:30:10,613 --> 00:30:11,815
MUTATION, MUTATION IN THE

765
00:30:11,815 --> 00:30:15,185
BINDING REGION AND THEN 2 IN THE

766
00:30:15,185 --> 00:30:18,054
TRANSMEMBRANE DOMAIN WHERE IT

767
00:30:18,054 --> 00:30:21,958
WAS LINKED TO THE LESION OF THE

768
00:30:21,958 --> 00:30:24,260
CCR4, WILD-TYPE CCR4 SO PATIENTS

769
00:30:24,260 --> 00:30:26,396
DO ACQUIRE GENETIC MUTATIONS IN

770
00:30:26,396 --> 00:30:28,731
THE CCR INCLUDING THE LESIONS

771
00:30:28,731 --> 00:30:30,667
THAT RESULT IN LACK OF

772
00:30:30,667 --> 00:30:33,069
EXPRESSION THAT WE SEE IN THE

773
00:30:33,069 --> 00:30:34,337
PHENOTYPIC EXPRESSION AND THE

774
00:30:34,337 --> 00:30:38,475
PATIENTS DON'T RESPOND BE TO THE

775
00:30:38,475 --> 00:30:39,676
DRUG ANYMORE.

776
00:30:39,676 --> 00:30:45,014
AND WE TRANSVECTED THE COUPLE OF

777
00:30:45,014 --> 00:30:48,751
PATIENTS, THE VARIANTS INTO

778
00:30:48,751 --> 00:30:50,820
JERKIT CELLS WHICH RESULT INDEED

779
00:30:50,820 --> 00:30:52,755
DECREASE OF CCR EXPRESSION

780
00:30:52,755 --> 00:30:53,656
COMPARED TO WILD-TYPE, SO ORANGE

781
00:30:53,656 --> 00:30:55,191
AND GREEN ARE THE TRANSFECTIVE

782
00:30:55,191 --> 00:30:57,627
1S THAT HAVE A DEE CREASE IN

783
00:30:57,627 --> 00:30:59,929
EXPRESSION XTHIS ALSO LED TO

784
00:30:59,929 --> 00:31:01,164
DECREASING THE ADCC FURCHG,

785
00:31:01,164 --> 00:31:02,365
AGAIN THE OVERWHELMING AND GREEN

786
00:31:02,365 --> 00:31:06,002
MUCH LESS THAN THE WILD-TYPE, SO

787
00:31:06,002 --> 00:31:06,569
CONFIRMING THE FUNCTIONAL

788
00:31:06,569 --> 00:31:08,738
ABNORMALITY IF YOU HAVE THESE

789
00:31:08,738 --> 00:31:10,106
VARIANTS.

790
00:31:10,106 --> 00:31:13,776
SO IN SUMMARY, RESISTANCE TO

791
00:31:13,776 --> 00:31:14,744
THIS APPROVED DRUG, SIGNIFICANT

792
00:31:14,744 --> 00:31:16,579
NUMBER OF PATIENTS HAVE LOSS OF

793
00:31:16,579 --> 00:31:18,047
THE TARGET, SOME OF WHICH COULD

794
00:31:18,047 --> 00:31:21,150
BE LINKED TO GENETIC MUTATION

795
00:31:21,150 --> 00:31:22,085
THAT THEY APPLY UNDER PRESSURE

796
00:31:22,085 --> 00:31:24,821
OF THE DRUG, AND THEN OTHER 1S

797
00:31:24,821 --> 00:31:26,289
WE CAN'T FIND A MUTATION AND

798
00:31:26,289 --> 00:31:28,191
THEP, WE HAVE PATIENTS WHO

799
00:31:28,191 --> 00:31:29,592
RETAIN THE EXPRESSION AND WE

800
00:31:29,592 --> 00:31:32,128
STILL NEED TO FIND OUT WHY THE

801
00:31:32,128 --> 00:31:33,830
RESISTANCE OCCURS IN THAT

802
00:31:33,830 --> 00:31:34,497
SUBSET, BUT IT'S ACTIVITIES AND

803
00:31:34,497 --> 00:31:36,232
PROJECTS EXAMPLE OF HOW WE GET

804
00:31:36,232 --> 00:31:39,068
THE DRUG, WE LEARN ABOUT THE

805
00:31:39,068 --> 00:31:40,003
BIOMARKERS OF RESPONSE AND

806
00:31:40,003 --> 00:31:43,606
RESISTANCE BECAUSE BY DOING

807
00:31:43,606 --> 00:31:48,444
THAT, HOPEFULLY WE CAN IMPROVE

808
00:31:48,444 --> 00:31:49,679
THE ACTIVITY, IS THAT THE TARGET

809
00:31:49,679 --> 00:31:51,614
WE NEED TO INCREASE OR ARE THERE

810
00:31:51,614 --> 00:31:53,149
OTHER PARTNERS WE CAN COMBINE.

811
00:31:53,149 --> 00:32:01,925
SO IN THIS PATIENTS WITH SEZARY

812
00:32:01,925 --> 00:32:03,226
SYNDROME, THE BLOOD TEASE WE

813
00:32:03,226 --> 00:32:04,894
CLEARED WITH MOGAMULIZUMAB, AND

814
00:32:04,894 --> 00:32:07,864
NOW THE PATIENT BECAME MORE LIKE

815
00:32:07,864 --> 00:32:09,299
THE MF PATIENT WITH

816
00:32:09,299 --> 00:32:11,568
[INDISCERNIBLE] DISEASE BUT WITH

817
00:32:11,568 --> 00:32:13,336
THICK PLAQUES AND TUMOROT SKIN.

818
00:32:13,336 --> 00:32:16,172
SO WHEN WE BIOPSIES AT THIS TIME

819
00:32:16,172 --> 00:32:18,308
POINT, THE SKIN BIOPSY DID SHOW

820
00:32:18,308 --> 00:32:19,309
LARGE CELL TRANSFORMATION AND

821
00:32:19,309 --> 00:32:22,879
THE PATIENT UPDATING THE SKIN

822
00:32:22,879 --> 00:32:24,480
SHOWED LYMPHNODE DEC.

823
00:32:24,480 --> 00:32:26,983
SO THEY HAVE A VERY DYNAMIC

824
00:32:26,983 --> 00:32:29,118
COURSE IS IN THE PATIENT WITH

825
00:32:29,118 --> 00:32:30,687
LYMPHNODE DEC WITH LARGE CELL

826
00:32:30,687 --> 00:32:31,621
TRANSFORMATION, THEN WE LOOK AT

827
00:32:31,621 --> 00:32:33,156
WHAT IS THE DATA OUT THERE THAT

828
00:32:33,156 --> 00:32:38,394
WOULD BE A GOOD MATCH AND THE

829
00:32:38,394 --> 00:32:42,632
MOST RIGOROUSLY STUDIED IN LARGE

830
00:32:42,632 --> 00:32:45,134
CELL TRANSFORMATION IS RETUX MAB

831
00:32:45,134 --> 00:32:46,536
WITH GOOD CLINICAL ACTIVITY

832
00:32:46,536 --> 00:32:48,571
WHERE THE TRANSFORMED PATIENTS

833
00:32:48,571 --> 00:32:49,639
HAVE A BETTER ACTIVITY THAN

834
00:32:49,639 --> 00:32:53,309
THOSE IN THE LUNG DEC SO IT'S A

835
00:32:53,309 --> 00:32:56,012
DRUG THAT COULD MATCH, ALIGN

836
00:32:56,012 --> 00:32:57,413
WELL WITH THE MORE AGGRESSIVE

837
00:32:57,413 --> 00:32:58,314
DISEASE, SO IN THIS PATIENT,

838
00:32:58,314 --> 00:32:59,949
WITH THE LARGE CELL

839
00:32:59,949 --> 00:33:00,650
TRANSFORMATION, LYMPHNODE DEC,

840
00:33:00,650 --> 00:33:07,123
IT WAS A VERY GOOD MATCH TO GIVE

841
00:33:07,123 --> 00:33:10,126
BREN TUX MAB, AND I WILL UTILIZE

842
00:33:10,126 --> 00:33:12,862
TO SEE HOW HARD THE TARGET

843
00:33:12,862 --> 00:33:15,398
IS,OOSE A VERY WELL KNOWN TARGET

844
00:33:15,398 --> 00:33:18,501
IN HUMAN O LOGIC DEC AND

845
00:33:18,501 --> 00:33:18,935
LYMPHOMA.

846
00:33:18,935 --> 00:33:20,737
IT TARGETS C30 LINKED WITH THE

847
00:33:20,737 --> 00:33:23,439
DRUG WHICH IS A [INDISCERNIBLE]

848
00:33:23,439 --> 00:33:24,707
INHIBITOR, IT GOES INSIDE THE

849
00:33:24,707 --> 00:33:26,175
CELL, RELEASES THE DRUG AND ALSO

850
00:33:26,175 --> 00:33:30,213
KILLS SOME OF THE CELLS THAT ARE

851
00:33:30,213 --> 00:33:32,749
CD30 NEGATIVE, IN THE PROXIMITY

852
00:33:32,749 --> 00:33:33,082
AS WELL.

853
00:33:33,082 --> 00:33:37,053
SO WE MAY ASK, SO WHAT IS THE

854
00:33:37,053 --> 00:33:39,222
DATA OUT THERE WITH THE TARGET

855
00:33:39,222 --> 00:33:40,056
EXPRESSION.

856
00:33:40,056 --> 00:33:42,692
AND AT STANFORD AND COLLEAGUES

857
00:33:42,692 --> 00:33:45,228
AT MD ANDERSON, WE'VE STUDIED

858
00:33:45,228 --> 00:33:46,863
THE RETUX MAB THAT WAS IMPROVED

859
00:33:46,863 --> 00:33:51,668
IN HODGE CONDITIONS AND ALCL BUT

860
00:33:51,668 --> 00:33:52,635
EXPORTED IN OUR DEC.

861
00:33:52,635 --> 00:33:54,837
BUT IT TURNS OUT IF YOU HAVE

862
00:33:54,837 --> 00:33:57,473
VERY HIGH CD30 EXPRESSION, THIS

863
00:33:57,473 --> 00:33:59,409
IS CD30 EXPRESSION, YELLOW IS

864
00:33:59,409 --> 00:34:01,577
THE NONRESPONDERS, BLUE ARE THE

865
00:34:01,577 --> 00:34:02,412
RESPONDING PATIENTS AND THIS

866
00:34:02,412 --> 00:34:03,846
Y-AXIS IS HOW MUCH REDUCTION YOU

867
00:34:03,846 --> 00:34:06,282
HAVE IN THE SKIN DISEASE.

868
00:34:06,282 --> 00:34:08,317
MINUS 100 BEING COMPLETELY

869
00:34:08,317 --> 00:34:08,518
CLEAR.

870
00:34:08,518 --> 00:34:11,154
SO THESE ARE THE GREAT

871
00:34:11,154 --> 00:34:12,822
RESPONDERS DOWN HERE AND THE

872
00:34:12,822 --> 00:34:15,725
CD30 LEVEL, IF YOU HAVE VERY

873
00:34:15,725 --> 00:34:16,693
HIGH EXPRESSION, RELIABLY THEY

874
00:34:16,693 --> 00:34:19,328
MAY HAVE GOOD RESPONSES AND DEEP

875
00:34:19,328 --> 00:34:21,230
RESPONSES BUT WHAT IS

876
00:34:21,230 --> 00:34:23,933
INTERESTING IS THAT IN THE LOW

877
00:34:23,933 --> 00:34:26,235
EXPRESSERS, 0-5%, YOU ALSO HAVE

878
00:34:26,235 --> 00:34:30,273
A MIX, A VERY GOOD RESPONSES AS

879
00:34:30,273 --> 00:34:31,040
WELL AS NONRESPONSE.

880
00:34:31,040 --> 00:34:32,508
SO IN THE HIGH EXPRESSION, IT'S

881
00:34:32,508 --> 00:34:34,744
GOOD TO CHOOSE THIS DRUG BECAUSE

882
00:34:34,744 --> 00:34:37,580
IT'S RELIABLE, BUT IT DIDN'T

883
00:34:37,580 --> 00:34:38,848
EXCLUDE YOU FROM CHOOSING THE

884
00:34:38,848 --> 00:34:42,652
DRUG IN THE REFRACTORY SETTING,

885
00:34:42,652 --> 00:34:44,787
EVEN WHEN YOU'RE

886
00:34:44,787 --> 00:34:46,489
IMMUNOHISTOCHEMISTRY CANNOT

887
00:34:46,489 --> 00:34:46,789
DETECT CD30.

888
00:34:46,789 --> 00:34:50,693
SO YOU MAY ASK, WELL, WHY IS THE

889
00:34:50,693 --> 00:34:53,362
TARGET NOT THERE, AND IT STILL

890
00:34:53,362 --> 00:34:54,063
CAN WORK.

891
00:34:54,063 --> 00:34:59,702
SO HERE'S A PATIENT WITH WIDE

892
00:34:59,702 --> 00:35:00,336
SPREAD, TRANSFORMATION AND THIS

893
00:35:00,336 --> 00:35:04,440
IS THE LESION THAT WE BIOPSIED

894
00:35:04,440 --> 00:35:07,410
WHICH SHOWS 0% CD30 BY

895
00:35:07,410 --> 00:35:09,579
IMMUNOHISTOCHEMISTRY WITH OUR

896
00:35:09,579 --> 00:35:12,148
EYES AND YOU GIVE BREN TUX MAB

897
00:35:12,148 --> 00:35:16,185
AND YOU CAN SEE THAT CLEARLY THE

898
00:35:16,185 --> 00:35:17,019
LESION HAS REGRESSED.

899
00:35:17,019 --> 00:35:19,288
SO TIMES THE TARGET EXPRESSION,

900
00:35:19,288 --> 00:35:20,356
DETECTION MAY BE A MATTER OF

901
00:35:20,356 --> 00:35:23,392
WHAT METHOD YOU USE, SO IF YOU

902
00:35:23,392 --> 00:35:25,895
USE A MORE SENSITIVE TOOL SUCH

903
00:35:25,895 --> 00:35:28,297
AS MULTISPECTRAL IMAGING, THEN

904
00:35:28,297 --> 00:35:32,368
YOU CAN SEE THAT THIS IS GREEN

905
00:35:32,368 --> 00:35:34,170
LINE THRESHOLD VISIBILITY WITH

906
00:35:34,170 --> 00:35:35,071
THE EYE WITH

907
00:35:35,071 --> 00:35:36,172
IMMUNOHISTOCHEMISTRY BUT THE

908
00:35:36,172 --> 00:35:39,375
MOLECULES EXIST IN CD30 WAY

909
00:35:39,375 --> 00:35:40,743
BELOW THE DETECTION THRESHOLD,

910
00:35:40,743 --> 00:35:42,712
SO MOLECULES ARE THERE IN MAYBE

911
00:35:42,712 --> 00:35:44,013
A MATTER OF IT'S NOT NEGATIVE,

912
00:35:44,013 --> 00:35:46,816
BUT WHAT YOU CAN DETECT WITH THE

913
00:35:46,816 --> 00:35:49,252
EYE, SO THE DRUG IS VERY

914
00:35:49,252 --> 00:35:51,754
POWERFUL, WORKED WITH VERY LOW

915
00:35:51,754 --> 00:35:52,555
AMOUNT OF MOLECULES.

916
00:35:52,555 --> 00:35:55,291
SO AGAIN, THEN THE DRUG SHOULD

917
00:35:55,291 --> 00:35:56,659
BE WHEN YOU BIOPSY A PATIENT

918
00:35:56,659 --> 00:35:58,728
WITH DIFFERENT DISEASE, THE

919
00:35:58,728 --> 00:36:01,831
MOLECULE MAY BE VERY VARIABLE IN

920
00:36:01,831 --> 00:36:02,431
EXPRESSION DIFFERENT PARTS OF

921
00:36:02,431 --> 00:36:03,800
THE BODY.

922
00:36:03,800 --> 00:36:05,735
SO THE PIVOTAL TRIAL SHOWS THAT

923
00:36:05,735 --> 00:36:07,136
YOU HAVE VERY DIFFERENT LEVELS

924
00:36:07,136 --> 00:36:10,139
OF EXPRESSION, EACH PATIENT IS

925
00:36:10,139 --> 00:36:10,506
[INDISCERNIBLE].

926
00:36:10,506 --> 00:36:12,375
YOU CAN SEE THE HIGH VARIETY OF

927
00:36:12,375 --> 00:36:13,676
EXPRESSION IF YOU BIOPSY

928
00:36:13,676 --> 00:36:15,745
MULTIPLE LESIONS WITHIN THE

929
00:36:15,745 --> 00:36:18,247
PATIENT, AND BLUE BEING

930
00:36:18,247 --> 00:36:19,215
RESPONDER, RED BEING

931
00:36:19,215 --> 00:36:20,249
NONRESPONDERS, CAN YOU SEE THAT

932
00:36:20,249 --> 00:36:22,985
IT DOESN'T REALLY HAVE A GOOD

933
00:36:22,985 --> 00:36:24,253
PREDICTION OF THE EXPRESSION

934
00:36:24,253 --> 00:36:26,689
LEVEL WITH THE RESPONSE PROFILE.

935
00:36:26,689 --> 00:36:31,494
THUS WE DO NOT USE CD30 TO

936
00:36:31,494 --> 00:36:32,862
ULTIMATELY GUIDE TREATMENT

937
00:36:32,862 --> 00:36:36,032
SELECTION BECAUSE ESPECIALLY IN

938
00:36:36,032 --> 00:36:36,666
THE REFRACTORY SETTING.

939
00:36:36,666 --> 00:36:38,835
ANOTHER WAY TO SHOW THE

940
00:36:38,835 --> 00:36:39,902
HETEROGENEITY IS THAT WITHIN THE

941
00:36:39,902 --> 00:36:44,006
SAME PATIENT, CAN YOU USE A MUCH

942
00:36:44,006 --> 00:36:46,309
MORE SPATIALLY SUPERIOR

943
00:36:46,309 --> 00:36:48,277
TECHNIQUES LIKE CO DECKS AND

944
00:36:48,277 --> 00:36:50,079
THEN LOOKING AT THE PATCH WORK

945
00:36:50,079 --> 00:36:50,880
WITHIN A PATIENT, CAN YOU SEE

946
00:36:50,880 --> 00:36:53,583
THAT THE TUMOR PROFILE, THE

947
00:36:53,583 --> 00:36:55,718
TISSUE MICROENVIRONMENT PROVIDES

948
00:36:55,718 --> 00:36:57,353
VERY HETEROGENIUS WITHIN THE

949
00:36:57,353 --> 00:36:59,522
PATIENT AGAIN DEMON TRAITING THE

950
00:36:59,522 --> 00:37:00,389
HETEROGENEITY WITHIN A LESION,

951
00:37:00,389 --> 00:37:02,325
CAN YOU SEE THAT DEPENDING ON

952
00:37:02,325 --> 00:37:06,829
WHICH CORE YOU BIOPSY, THAT

953
00:37:06,829 --> 00:37:07,864
COULD BE STRIKING HETEROGENEITY

954
00:37:07,864 --> 00:37:12,668
IN THE LESION PROFILE.

955
00:37:12,668 --> 00:37:15,671
THUS THE CAUTIONARY WORD IN THE

956
00:37:15,671 --> 00:37:20,676
CTCL IS THAT YOU NEED TO TAKE

957
00:37:20,676 --> 00:37:22,879
MULTIPLE SAMPLES BECAUSE IT'S

958
00:37:22,879 --> 00:37:23,613
VERY HETEROGENIUS CLINICALLY,

959
00:37:23,613 --> 00:37:27,950
AND IN THE BIOMARKER GUIDED

960
00:37:27,950 --> 00:37:28,251
MANAGEMENT.

961
00:37:28,251 --> 00:37:32,922
SO NOW I WILL TALK ABOUT A

962
00:37:32,922 --> 00:37:34,924
LITTLE BIT OF CELL THERAPIES, IN

963
00:37:34,924 --> 00:37:36,626
ADVANCE DISEASE WHERE WE WANT TO

964
00:37:36,626 --> 00:37:40,196
CURE PATIENTS, WE DO NEDRA TO

965
00:37:40,196 --> 00:37:41,697
UTILIZE TREATMENTS THAT CAN BE

966
00:37:41,697 --> 00:37:47,136
MORE INTENSIVE AND B-CELL

967
00:37:47,136 --> 00:37:47,970
LYMPHOMAS, OBVIOUSLY CAR-Ts

968
00:37:47,970 --> 00:37:50,506
HAVE BEEN GREATLY BENEFICIAL AND

969
00:37:50,506 --> 00:37:53,276
IN CTCL, IT'S BEEN MORE

970
00:37:53,276 --> 00:37:53,976
DIFFICULT.

971
00:37:53,976 --> 00:37:56,212
AND WE HAVE IN CELL THERAPIES,

972
00:37:56,212 --> 00:37:59,115
WE HAVE OUR DONOR STEM CELL

973
00:37:59,115 --> 00:38:01,817
WHICH DOESN'T TARGET A SPECIFIED

974
00:38:01,817 --> 00:38:03,819
DEFINED TARGET BUT IN CAR-T, YOU

975
00:38:03,819 --> 00:38:06,722
CAN TARGET A DEFINED MORE

976
00:38:06,722 --> 00:38:09,892
SPECIFIC TARGET AND THE REASON

977
00:38:09,892 --> 00:38:19,869
IN T-CELL, THE FOCUS HAS BEEN

978
00:38:19,869 --> 00:38:22,405
SLOW, IS THAT CAR-Ts ARE A

979
00:38:22,405 --> 00:38:24,106
LYMPHOMA, SO DEPENDING ON WHICH

980
00:38:24,106 --> 00:38:25,875
TARGET YOU SELECT, YOU MAY BE

981
00:38:25,875 --> 00:38:28,544
THE T-CELLS MAY BE KILLING EACH

982
00:38:28,544 --> 00:38:31,580
OTHER, TO TRY TO ATTACK A T-CELL

983
00:38:31,580 --> 00:38:33,316
MARKER, IN A T-CELL LYMPHOMA SO

984
00:38:33,316 --> 00:38:37,553
YOU DON'T WANT TO WORRY ABOUT

985
00:38:37,553 --> 00:38:39,188
THE FRACTURE SIDE OF THE T-CELLS

986
00:38:39,188 --> 00:38:40,756
ILLEGALS CANNING EACH OTHER, SO

987
00:38:40,756 --> 00:38:45,027
NOW WITH THE IMMUNE EDITING,

988
00:38:45,027 --> 00:38:47,730
CRSPR, AND OTHER EDITING

989
00:38:47,730 --> 00:38:50,766
TECHNIQUES, THE CAR-Ts ARE

990
00:38:50,766 --> 00:38:51,767
BETTER MODIFIED SO YOU CAN

991
00:38:51,767 --> 00:38:53,970
REMOVE THOSE TARGETING SYSTEMYS

992
00:38:53,970 --> 00:38:55,805
WITHIN THE CAR-T.

993
00:38:55,805 --> 00:38:57,006
BUT TARGET THE MALIGNANCY AND

994
00:38:57,006 --> 00:38:59,041
SOME OF THOSE ADVANCEMENTS HAVE

995
00:38:59,041 --> 00:39:04,246
BEEN IN THE CD7, TRBC1, CD30 AND

996
00:39:04,246 --> 00:39:04,480
OTHERS.

997
00:39:04,480 --> 00:39:08,117
AND SO NOW I THINK YOU WOULD SEE

998
00:39:08,117 --> 00:39:11,487
MORE ADVANCES IN THE CAR-T

999
00:39:11,487 --> 00:39:13,089
THERAPY AND T-CELL LYMPHOMA.

1000
00:39:13,089 --> 00:39:14,590
THE MORE COMMONLY UTILIZED CELL

1001
00:39:14,590 --> 00:39:16,759
THERAPY IS THE STEM CELL

1002
00:39:16,759 --> 00:39:19,962
TREATMENT, AND WE ASK THEM, WHAT

1003
00:39:19,962 --> 00:39:21,664
ARE--WHO DO WE TRANSPLANT, WELL,

1004
00:39:21,664 --> 00:39:22,965
IN THE ADVANCED DISEASE, YOU SEE

1005
00:39:22,965 --> 00:39:27,103
THE RISK PROFILE THAT I

1006
00:39:27,103 --> 00:39:28,571
MENTIONED AND WE WOULD NOW

1007
00:39:28,571 --> 00:39:30,039
TRANSPLANT BECAUSE OF THE

1008
00:39:30,039 --> 00:39:31,340
COMPLICATIONS OF THE TRANSPLANT

1009
00:39:31,340 --> 00:39:32,608
SIZE, IN THE PEASHT WHO IS HAD

1010
00:39:32,608 --> 00:39:33,943
LOW RISK BUT DEFINITELY IN THE

1011
00:39:33,943 --> 00:39:36,278
HIGH RISK AND IN THE ISHT

1012
00:39:36,278 --> 00:39:39,382
MEDIATE RISK PATIENTS WE

1013
00:39:39,382 --> 00:39:40,750
CONSIDER A TRANSPLANT SOONER OR

1014
00:39:40,750 --> 00:39:42,752
WHEN YOUR TREATMENTS BECOME VERY

1015
00:39:42,752 --> 00:39:44,286
REFRACTORY, YOU WOULD CONSIDER

1016
00:39:44,286 --> 00:39:46,355
THAT BECAUSE YOU WOULD THEN RUN

1017
00:39:46,355 --> 00:39:48,991
OUT OF TREATMENTS AND THEN YOU

1018
00:39:48,991 --> 00:39:50,760
MAY NOT BE ABLE TO CLEAR THE

1019
00:39:50,760 --> 00:39:52,628
PATIENT TO GET THEM INTO

1020
00:39:52,628 --> 00:39:53,095
TRANSPLANT.

1021
00:39:53,095 --> 00:39:59,201
SO THE TRANSPLANT DATA AT OUR

1022
00:39:59,201 --> 00:40:02,238
CENTER, USING TOTAL LYMPHOID

1023
00:40:02,238 --> 00:40:04,573
GLOBUE LYNN AS A CONDIGGING, WE

1024
00:40:04,573 --> 00:40:06,142
SHOWED GOOD OVERALL RESPONSE AND

1025
00:40:06,142 --> 00:40:08,978
OVERALL SURVIVAL RATES OF ABOUT

1026
00:40:08,978 --> 00:40:10,780
60%, AND THIS IS MUCH BETTER

1027
00:40:10,780 --> 00:40:12,415
THAN A NATURAL COURSE OF SIMILAR

1028
00:40:12,415 --> 00:40:17,887
PATIENT, WHERE THE HIGH RISK

1029
00:40:17,887 --> 00:40:23,926
PATIENTS MAY BE 30%, SO IT MAY

1030
00:40:23,926 --> 00:40:25,961
BE BETTER WITH THE OVERALL

1031
00:40:25,961 --> 00:40:29,265
SURVIVAL, AND THOSE PATIENTS

1032
00:40:29,265 --> 00:40:30,800
WITH NEGATIVE MOLECULAR DISEASE

1033
00:40:30,800 --> 00:40:32,635
ARE OBVIOUSLY PSYCHED THEY'RE

1034
00:40:32,635 --> 00:40:33,836
MORE CURED, SO THEY DO BETTER

1035
00:40:33,836 --> 00:40:36,572
AND IF YOU LOOK AT ACROSS ALL

1036
00:40:36,572 --> 00:40:44,447
THE CENTERS A KEY STEM CELL,

1037
00:40:44,447 --> 00:40:45,981
TRANSPLANT DATA, THE STANFORD

1038
00:40:45,981 --> 00:40:48,150
CONDITIONING BECAUSE IT'S A

1039
00:40:48,150 --> 00:40:49,718
MILDER NONAPLATIVE REGIMEN, IT

1040
00:40:49,718 --> 00:40:51,687
DOES ALLOW OLDER PATIENTS TO BE

1041
00:40:51,687 --> 00:40:53,022
TRANSPLANTED AND THIS IS

1042
00:40:53,022 --> 00:40:56,358
RELEVANT BECAUSE THE MEDIAN AGE

1043
00:40:56,358 --> 00:40:57,660
OF THE CTCL PATIENT IS OLDER SO

1044
00:40:57,660 --> 00:40:59,695
WE DO WANT TO TRY TO OFFER THE

1045
00:40:59,695 --> 00:41:00,696
TRANSPLANT TO THE OLDER

1046
00:41:00,696 --> 00:41:03,833
POPULATION BUT A LOT OF PATIENTS

1047
00:41:03,833 --> 00:41:05,267
ARE NOT TRANSPLANT ELIGIBLE, OR

1048
00:41:05,267 --> 00:41:06,635
THEY DON'T HAVE MATCHES, THAT'S

1049
00:41:06,635 --> 00:41:08,938
WHY WE NEED TO IMPROVE OTHER

1050
00:41:08,938 --> 00:41:10,806
CELL THERAPIES AS WELL, BUT WE

1051
00:41:10,806 --> 00:41:13,008
HAVE SIMILAR DATA REGARDLESS OF

1052
00:41:13,008 --> 00:41:14,877
THE TRANSPLANT PROTOCOL, BUT OUR

1053
00:41:14,877 --> 00:41:18,814
METHOD DOES ALLOW OLDER PATIENT

1054
00:41:18,814 --> 00:41:19,515
POPULATION FOR TRANSPLANT.

1055
00:41:19,515 --> 00:41:22,618
SO IN THIS PATIENT, WITH SENSORY

1056
00:41:22,618 --> 00:41:25,855
STARTED WITH HYBRID LEUKEMIC

1057
00:41:25,855 --> 00:41:27,723
DISEASE WHICH WE WERE ABLE TO

1058
00:41:27,723 --> 00:41:29,091
CLEAR WITH MOGAMULIZUMAB, HE

1059
00:41:29,091 --> 00:41:34,830
TURNED MORE INTO AN MF PROFILE,

1060
00:41:34,830 --> 00:41:36,031
LYMPHNODE DISEASE, WE ALIGNED

1061
00:41:36,031 --> 00:41:37,900
THE TREATMENT THAT WORKED WELL

1062
00:41:37,900 --> 00:41:40,202
IN THAT PROFILE AND THEN

1063
00:41:40,202 --> 00:41:41,303
EEIVETTUALLY BECAUSE HE'S HIGH

1064
00:41:41,303 --> 00:41:43,172
RISK WITH EMILY NODE DISEASE, WE

1065
00:41:43,172 --> 00:41:45,741
GOT HIM TO ALOE TRANSPLANT, HE

1066
00:41:45,741 --> 00:41:47,276
SUCCESSFULLY KNOWN THROUGH OUR

1067
00:41:47,276 --> 00:41:48,110
TRANSPLANT PROGRAM, WE'RE ABOUT

1068
00:41:48,110 --> 00:41:52,448
A YEAR OUT NOW AND WITHOUT GBH

1069
00:41:52,448 --> 00:41:57,353
AND HAVING PROLONG CURATIVE,

1070
00:41:57,353 --> 00:42:00,990
HOPEFULLY CURATIVE REMISSION.

1071
00:42:00,990 --> 00:42:02,691
DESPITE THE HETEROGENEITY OF THE

1072
00:42:02,691 --> 00:42:04,326
CLINICAL DIVERSE PROFILE,

1073
00:42:04,326 --> 00:42:06,629
INTERESTING THAT THEIR TCR

1074
00:42:06,629 --> 00:42:08,531
DOMINANT TCR SEQUENCE IS

1075
00:42:08,531 --> 00:42:10,032
IDENTICAL WHICH GIVES A CLUE

1076
00:42:10,032 --> 00:42:15,371
THAT MAYBE THE TCR IS A GOOD

1077
00:42:15,371 --> 00:42:17,139
TARGET REGARDLESS OF PATIENT

1078
00:42:17,139 --> 00:42:18,340
TRANSITIONING INTO THIS DYNAMIC

1079
00:42:18,340 --> 00:42:20,342
PROFILE, WE DO HAVE A CONSTANT

1080
00:42:20,342 --> 00:42:23,345
VARIABLE WHICH IS THE TCR THAT'S

1081
00:42:23,345 --> 00:42:25,214
REARK RANGED IN THE T-CELL

1082
00:42:25,214 --> 00:42:27,283
LYMPHOMA AND MAYBE COULD BE A

1083
00:42:27,283 --> 00:42:30,119
TARGET FOR EITHER ANTIBODY CELL

1084
00:42:30,119 --> 00:42:33,455
THERAPIES, ANY OF THESE

1085
00:42:33,455 --> 00:42:35,658
VACCINATIONS AND AT STANFORD

1086
00:42:35,658 --> 00:42:37,660
WE'RE WORKING ON VACCINATION

1087
00:42:37,660 --> 00:42:38,627
TECHNIQUE TARGETING TCR.

1088
00:42:38,627 --> 00:42:47,102
SO WHAT'S NEXT IN CTCL?

1089
00:42:47,102 --> 00:42:55,344
WE HAVE A LOT'VE THERAPY AND

1090
00:42:55,344 --> 00:42:56,679
-THERAPIES AND WE NEED TO

1091
00:42:56,679 --> 00:42:58,113
LEARN MORE ABOUT BIOMARKERS AND

1092
00:42:58,113 --> 00:43:03,886
HOW TO UTILIZE THEM IN PRACTICE 

1093
00:43:03,886 --> 00:43:06,322
IN ORDER TO DO DATA TRIALS.

1094
00:43:06,322 --> 00:43:08,524
SO HIGHLY ENCOURAGE UTILIZING

1095
00:43:08,524 --> 00:43:10,526
BIOMARKERS IN YOUR TRIAL, IF YOU

1096
00:43:10,526 --> 00:43:12,828
HAVE BIOMARKER DRIVEN TRIALS IF

1097
00:43:12,828 --> 00:43:15,130
POSSIBLE, WE HAVE FORTUNATELY A

1098
00:43:15,130 --> 00:43:17,266
MULTITUDE OF COOL TOOLS TO HELP

1099
00:43:17,266 --> 00:43:19,101
PROFILE THE TUMOR, THE

1100
00:43:19,101 --> 00:43:21,003
MICROENVIRONMENT, TISSUE AND

1101
00:43:21,003 --> 00:43:21,704
BLOOD COMPARTMENTS, AND DON'T

1102
00:43:21,704 --> 00:43:24,006
HAVE TIME TO GO INTO ALL OF THEM

1103
00:43:24,006 --> 00:43:31,413
BUT WANTED TO HIGHLIGHT ONCE

1104
00:43:31,413 --> 00:43:34,116
AGAIN, NOW, A LOT OF CENTERS AND

1105
00:43:34,116 --> 00:43:35,417
GIVEN COMMERCIAL ENTERPRISES

1106
00:43:35,417 --> 00:43:36,752
THAT OFFER MOLECULAR PROFILING

1107
00:43:36,752 --> 00:43:37,686
OF THE CANCER.

1108
00:43:37,686 --> 00:43:40,689
WE DO UTILIZE THIS IN OUR

1109
00:43:40,689 --> 00:43:42,291
REFRACTORY SETTING, JUST AS AN

1110
00:43:42,291 --> 00:43:44,193
EXAMPLE, IN THE JACK STAT

1111
00:43:44,193 --> 00:43:45,928
SIGNALING THAT'S VERY RELEVANT

1112
00:43:45,928 --> 00:43:48,664
IN CTCL, AND IT IS NOT VERY

1113
00:43:48,664 --> 00:43:54,536
COMMON TO HAVE PATHOGENIC

1114
00:43:54,536 --> 00:43:57,773
VARIANTS BUT WE DO SEE THAT

1115
00:43:57,773 --> 00:43:59,808
PATIENTS TUMOR ACQUIRING

1116
00:43:59,808 --> 00:44:01,277
MUTATIONS WITHIN IT WHEN THEIR

1117
00:44:01,277 --> 00:44:04,179
DISEASE BECOMES MORE

1118
00:44:04,179 --> 00:44:05,414
AGGRESSIVEENTIOUS SPECIALLY WITH

1119
00:44:05,414 --> 00:44:06,982
LARGE CELL TRANSFORMATION, SO IT

1120
00:44:06,982 --> 00:44:08,417
IS VERY RELEVANT IN OUR DISEASE

1121
00:44:08,417 --> 00:44:11,720
AND MAKING THEM ACCELERATE AND

1122
00:44:11,720 --> 00:44:12,788
MAKING THEM MORE AGGRESSIVE.

1123
00:44:12,788 --> 00:44:15,724
WE DO SEE SOME RARE JACK 2

1124
00:44:15,724 --> 00:44:18,761
VARIANTS INCLUDING FUSION

1125
00:44:18,761 --> 00:44:19,561
MOLECULES DEMON TRAITING

1126
00:44:19,561 --> 00:44:22,831
EXAMPLE, BUT THERE'S BEEN A

1127
00:44:22,831 --> 00:44:25,200
TRIAL IN T-CELL LYMPHOMA,

1128
00:44:25,200 --> 00:44:29,972
HOWEVER THE TRIAL SHOWED ONLY

1129
00:44:29,972 --> 00:44:31,640
14%, RESPONSE FOR AND HOWEVER,

1130
00:44:31,640 --> 00:44:34,510
IT WAS NOT ENRICHED FOR THE

1131
00:44:34,510 --> 00:44:37,813
GENETIC VARIANTS, SO IT WASN'T

1132
00:44:37,813 --> 00:44:39,948
ALIGNED THAT IF YOU HAVE JACK 2

1133
00:44:39,948 --> 00:44:43,485
MUTATION OR FUSION, YOU SHOULD

1134
00:44:43,485 --> 00:44:44,987
USE MOGAMULIZUMAB, SO IT WASN'T

1135
00:44:44,987 --> 00:44:45,821
ALIGNED THAT WAY.

1136
00:44:45,821 --> 00:44:48,390
SO IN OUR PATIENT TO DEMONSTRATE

1137
00:44:48,390 --> 00:44:51,694
WE THIS ALIGN BETTER PERHAPS IN

1138
00:44:51,694 --> 00:44:56,665
THE FUTURE IS THAT TO USE THE

1139
00:44:56,665 --> 00:44:58,467
PATIENT WHO WE HAD OFFLABEL,

1140
00:44:58,467 --> 00:45:00,135
THIS WOULD BE OFFLABEL USE

1141
00:45:00,135 --> 00:45:04,506
OTHERS PATIENT WITH 2 B, WITH

1142
00:45:04,506 --> 00:45:06,508
LCT, WITH MULTIPLE LINES OF

1143
00:45:06,508 --> 00:45:07,543
THERAPY AND RADIATIONS, IT

1144
00:45:07,543 --> 00:45:08,944
DOESN'T RESPOND TO RADIATION

1145
00:45:08,944 --> 00:45:14,917
WELL, BUT WE FOUND IT HAD AIAC 2

1146
00:45:14,917 --> 00:45:15,784
P[INDISCERNIBLE] MUTATION, WE

1147
00:45:15,784 --> 00:45:19,254
FOUND THIS WAS MORE OF A FOUNDER

1148
00:45:19,254 --> 00:45:22,391
MUTATION AND DOWN STREAM

1149
00:45:22,391 --> 00:45:24,059
ACCELERATING VARIANT, SINCE SHE

1150
00:45:24,059 --> 00:45:25,260
FAILED MULTIPLE STANDARD

1151
00:45:25,260 --> 00:45:29,231
THERAPIES WE DIDN'T USE

1152
00:45:29,231 --> 00:45:30,733
RUXOLITINIB, AND IN A FEW MONTHS

1153
00:45:30,733 --> 00:45:33,635
THIS IS THE 5 MONTH DATA SHE HAD

1154
00:45:33,635 --> 00:45:36,238
VERY DRAMATIC SHRINKAGE OF HER

1155
00:45:36,238 --> 00:45:38,040
TUMOR WHERE THE PRIOR THERAPIES

1156
00:45:38,040 --> 00:45:40,576
WERE NOT, WAS NOT ABLE TO SHRINK

1157
00:45:40,576 --> 00:45:42,111
IT EVEN RADIATION, SO CAN YOU

1158
00:45:42,111 --> 00:45:43,245
SEE THE DRAMATIC CHANGE.

1159
00:45:43,245 --> 00:45:45,514
SO WE HOPE THAT UTILIZING SUCH

1160
00:45:45,514 --> 00:45:47,216
STRATEGY COULD HELP IN THE

1161
00:45:47,216 --> 00:45:49,485
FUTURE AND DESIGNING TRIALS AS

1162
00:45:49,485 --> 00:45:50,386
WELL.

1163
00:45:50,386 --> 00:45:52,154
ANOTHER EXAMPLE OF OF ACTIONABLE

1164
00:45:52,154 --> 00:46:00,195
NG S PROFILE WOULD BE A TEMPORAL

1165
00:46:00,195 --> 00:46:01,597
[INDISCERNIBLE] TRIAL BUT AGAIN

1166
00:46:01,597 --> 00:46:04,233
THE RESPONSE WAS ABOUT 30%,

1167
00:46:04,233 --> 00:46:05,734
WHICH IS THE STANDARD RESPONSE

1168
00:46:05,734 --> 00:46:08,337
RATE FOR ALL THE CTCL TRIALS IF

1169
00:46:08,337 --> 00:46:10,706
YOU DON'T ENRICH BUT SOME OF THE

1170
00:46:10,706 --> 00:46:13,208
PATIENTS WITH LCT HAVE PDL 1

1171
00:46:13,208 --> 00:46:14,143
STRUCTURAL VARIANT ANDS IN THOSE

1172
00:46:14,143 --> 00:46:18,280
PATE WHEN IS WE SEE THAT, WHEN

1173
00:46:18,280 --> 00:46:21,283
WE TARGET WITH PEMBRO, IT IS

1174
00:46:21,283 --> 00:46:23,419
MUCH HIGHER THAN 30%EM

1175
00:46:23,419 --> 00:46:24,186
SOPHISTICATED HAVE DRAMATIC

1176
00:46:24,186 --> 00:46:25,387
RESPONSES AND THAT ARE DURABLE.

1177
00:46:25,387 --> 00:46:29,892
AND THIS IS COB CYST EPT WITH

1178
00:46:29,892 --> 00:46:31,160
DATA USING MOGAMULIZUMAB AS

1179
00:46:31,160 --> 00:46:34,029
WELL, SO AGAIN, MAYBE WHEN WE

1180
00:46:34,029 --> 00:46:35,564
ENRICH OUR POPULATION OF

1181
00:46:35,564 --> 00:46:37,266
PATIENTS WHO CAN BENEFIT WE CAN

1182
00:46:37,266 --> 00:46:38,634
HAVE A BETTER RESULT, ESPECIALLY

1183
00:46:38,634 --> 00:46:40,002
IN THE RARE DISEASE, IT MAKES

1184
00:46:40,002 --> 00:46:42,404
MORE SENSE, AND AGAIN IN ORDER

1185
00:46:42,404 --> 00:46:46,208
TO WORK TOGETHER, AND WHEN WE

1186
00:46:46,208 --> 00:46:46,909
DISCOVER FINDINGS IN A CENTER,

1187
00:46:46,909 --> 00:46:52,014
WE WANT TO BE READY TO VALIDATE

1188
00:46:52,014 --> 00:46:54,950
OR DEMONSTRATE THE CRUCIATE

1189
00:46:54,950 --> 00:46:55,818
LIGAMENTTILITY OF THAT DISCOVERY

1190
00:46:55,818 --> 00:46:59,321
IN THE END SIZE SO IT CAN HAVE

1191
00:46:59,321 --> 00:47:01,290
GREATER IMPACT, BE MORE MEANING

1192
00:47:01,290 --> 00:47:01,523
EMPLOY.

1193
00:47:01,523 --> 00:47:04,426
SO WE BUILT THIS WITH OUR UK

1194
00:47:04,426 --> 00:47:04,927
COLLEAGUE, INTERNATIONAL

1195
00:47:04,927 --> 00:47:06,128
CONSORTIUM, NOW IT'S MORE THAN

1196
00:47:06,128 --> 00:47:10,132
70 CENTERS WHERE WE GATHER

1197
00:47:10,132 --> 00:47:11,400
PROSPECTIVE DATA TOGETHER, WE

1198
00:47:11,400 --> 00:47:12,501
BUILT A BIOBANK WITH THAT

1199
00:47:12,501 --> 00:47:16,138
PATIENT AND WITH LARGE CELL

1200
00:47:16,138 --> 00:47:16,872
TRANSFORMATION AND PROGRESSION

1201
00:47:16,872 --> 00:47:19,408
EVENTS AND WITH TREATMENT

1202
00:47:19,408 --> 00:47:19,675
RESPONSE.

1203
00:47:19,675 --> 00:47:24,646
WE HAVE A DIGITIZED PATHOLOGY

1204
00:47:24,646 --> 00:47:26,415
DATA BANK WHERE PATHOLOGY

1205
00:47:26,415 --> 00:47:29,051
LEADERS COULD UTILIZE THE PATH

1206
00:47:29,051 --> 00:47:31,053
SLIDES FOR PROJECTS, SO THIS HAS

1207
00:47:31,053 --> 00:47:36,291
BEEN BUILT, AND WE HOPE THAT

1208
00:47:36,291 --> 00:47:39,228
DISCOVERIES IN SINGLE CENTERS

1209
00:47:39,228 --> 00:47:44,066
COULD BE TESTED IN MUCH LARGER

1210
00:47:44,066 --> 00:47:45,300
SAMPLE SIZE TO BRING MORE

1211
00:47:45,300 --> 00:47:47,336
MEANINGFUL IMPACT AND WE WILL BE

1212
00:47:47,336 --> 00:47:49,972
READY TO DO SO MORE IN THE

1213
00:47:49,972 --> 00:47:50,405
FUTURE.

1214
00:47:50,405 --> 00:47:53,041
SO IT MAKES SENSE IN A RARE

1215
00:47:53,041 --> 00:47:55,244
DISEASE TO BUILD IN SUCH

1216
00:47:55,244 --> 00:47:58,447
PLATFORMS, SO IN SUMMARY,

1217
00:47:58,447 --> 00:48:00,482
DEMONSTRATE THAD IT IS HIGHLY

1218
00:48:00,482 --> 00:48:01,683
HETEROGENERATED YIEWS, WE HAVE

1219
00:48:01,683 --> 00:48:03,585
TO SPECIALIZE BECAUSE OF THE

1220
00:48:03,585 --> 00:48:04,520
TREATMENT VS DIFFERENTIAL

1221
00:48:04,520 --> 00:48:06,088
ACTIVITY NOT ONLY ACROSS SKIN

1222
00:48:06,088 --> 00:48:09,892
DEC, TYPINGS BUT ACROSS

1223
00:48:09,892 --> 00:48:11,860
COMPARTMENTS, WE HAVE TO ALWAYS

1224
00:48:11,860 --> 00:48:12,661
UPDATE THE DEPARTMENT ACTIVITY

1225
00:48:12,661 --> 00:48:14,563
BECAUSE OF THAT TO MATCH

1226
00:48:14,563 --> 00:48:17,399
ACCORDINGLY IN PATIENTS WITH

1227
00:48:17,399 --> 00:48:19,902
VERY HIGH RISK DISEASE,

1228
00:48:19,902 --> 00:48:21,003
OBVIOUSLY CURRENTLY WE SHOULD

1229
00:48:21,003 --> 00:48:22,671
CONSIDER TRANSPLANT BUT WE NEED

1230
00:48:22,671 --> 00:48:24,139
BETTER THERAPIES BUT LOWER

1231
00:48:24,139 --> 00:48:25,407
PATIENTS ARE NOT TRANSPLANT

1232
00:48:25,407 --> 00:48:33,081
ELIGIBLE, SO WE WOULD LOAMACYIC

1233
00:48:33,081 --> 00:48:33,982
--LIKE TO

1234
00:48:33,982 --> 00:48:36,652
HAVE MORE THERAPIES OR CELL

1235
00:48:36,652 --> 00:48:37,553
SPECIFIC TYPES.

1236
00:48:37,553 --> 00:48:39,555
AGAIN CAUTIONOT TISSUE OF

1237
00:48:39,555 --> 00:48:41,790
BIOMARKERS IN CTCL BECAUSE OF

1238
00:48:41,790 --> 00:48:45,160
THE HETEROGENEITY SO WE HAVE A

1239
00:48:45,160 --> 00:48:48,931
LOT OF INTRA PATIENT INTRA

1240
00:48:48,931 --> 00:48:52,334
LESIONAL, INTRA TOMB OARAL

1241
00:48:52,334 --> 00:48:52,668
HETEROGENEITY.

1242
00:48:52,668 --> 00:48:55,470
SO CAUTION OF THE BIOMARKERS AND

1243
00:48:55,470 --> 00:48:58,607
OBVIOUSLY WE NEED TO DO MUCH

1244
00:48:58,607 --> 00:48:59,841
BETTER IN THIS RARE DEC WITH

1245
00:48:59,841 --> 00:49:01,043
TREATMENTS THAT CAN BETTER MATCH

1246
00:49:01,043 --> 00:49:03,145
WITH THE PATIENTS SO IN THE

1247
00:49:03,145 --> 00:49:03,912
FUTURE WHEN WE DESIGN CLINICAL

1248
00:49:03,912 --> 00:49:05,581
TRIALS WE WANT TO ENRICH THOSE

1249
00:49:05,581 --> 00:49:07,282
WHO CAN BENEFIT, RATHER THAN

1250
00:49:07,282 --> 00:49:08,550
JUST GIVE 1 DRUG TO ALL PATIENTS

1251
00:49:08,550 --> 00:49:11,186
AND THEN COME UP WITH THE 30%

1252
00:49:11,186 --> 00:49:11,520
RESPONSE RATE.

1253
00:49:11,520 --> 00:49:14,890
SO WE WANT TO DO BETTER IN THAT

1254
00:49:14,890 --> 00:49:15,424
AREA.

1255
00:49:15,424 --> 00:49:18,293
SO I WANT TO THANK ALL OF MY

1256
00:49:18,293 --> 00:49:20,362
PARTNERS AT STANFORD, ESPECIALLY

1257
00:49:20,362 --> 00:49:22,931
MICHAEL [INDISCERNIBLE] WHO IS

1258
00:49:22,931 --> 00:49:23,966
OUR TRANSLATIONAL LEAD, WITHOUT

1259
00:49:23,966 --> 00:49:26,969
HIS GROUP, IT WOULD BE HARD TO

1260
00:49:26,969 --> 00:49:30,405
MAKE SENSE OF ANY CLINICAL

1261
00:49:30,405 --> 00:49:32,107
FINDINGS, AND/OR BRING DISCOVERY

1262
00:49:32,107 --> 00:49:35,444
TO OUR PATIENTS IN A SENSE OF

1263
00:49:35,444 --> 00:49:38,780
ALL FASHION, AND ALSO OUR HUGE

1264
00:49:38,780 --> 00:49:40,782
CLINICAL TEAM THAT WE CANNOT DO

1265
00:49:40,782 --> 00:49:43,285
WITHOUT ON A DAILY BASIS.

1266
00:49:43,285 --> 00:49:47,990
AND  HERE WE ALSO DO HAVE FUNDS

1267
00:49:47,990 --> 00:49:49,758
AND THAT'S ALL WITH MY TALK

1268
00:49:49,758 --> 00:49:54,296
TODAY AND REALLY APPRECIATE YOUR

1269
00:49:54,296 --> 00:49:57,366
ATTENTION THIS MORNING.

1270
00:49:57,366 --> 00:49:58,400
>> THANK YOU VERY MUCH DR.
KIM.

1271
00:49:58,400 --> 00:49:59,434
THAT WAS WONDERFUL AND

1272
00:49:59,434 --> 00:50:00,669
APPRECIATE SORT OF THE BROAD

1273
00:50:00,669 --> 00:50:02,037
PERSPECTIVE AS WELL AS SOME OF

1274
00:50:02,037 --> 00:50:04,506
THE DETAILS ABOUT THE MOLECULAR

1275
00:50:04,506 --> 00:50:06,475
PROFILING, I GUESS, MY FIRST

1276
00:50:06,475 --> 00:50:08,243
QUESTION SORT OF BIG PICTURE IS

1277
00:50:08,243 --> 00:50:10,712
JUST GIVEN THE AMOUNT OF

1278
00:50:10,712 --> 00:50:13,615
VARIABILITY AND RESPONSE TO

1279
00:50:13,615 --> 00:50:15,283
TREATMENTS AND AND THE VARIOUS

1280
00:50:15,283 --> 00:50:16,718
WAYS PEOPLE PRESENT AND

1281
00:50:16,718 --> 00:50:17,919
OBVIOUSLY THE PROGNOSIS THAT'S

1282
00:50:17,919 --> 00:50:20,922
DIFFERENT, I LIKE THE CONCEPT OF

1283
00:50:20,922 --> 00:50:22,591
CONPART AMS, BLOOD AND SKIN EVEN

1284
00:50:22,591 --> 00:50:25,794
WITHIN THE SKIN COMPARTMENT

1285
00:50:25,794 --> 00:50:27,763
WHERE YOU HAVE PATCH DISEASE

1286
00:50:27,763 --> 00:50:28,597
VERSUS TUMOR DISEASE, THOSE

1287
00:50:28,597 --> 00:50:31,700
PATIENTS ARE GOING TO HAVE A

1288
00:50:31,700 --> 00:50:32,367
DRAMATICALLY DIFFERENT

1289
00:50:32,367 --> 00:50:35,504
PROGNOSIS, YET WE STILL CALL ALL

1290
00:50:35,504 --> 00:50:37,105
THESE PATES CUTANEOUS T-CELL

1291
00:50:37,105 --> 00:50:40,108
LYMPHOMA SO ARE DOING A

1292
00:50:40,108 --> 00:50:41,343
DISSERVICE BY CONSIDERING THIS

1293
00:50:41,343 --> 00:50:42,044
ALL 1 DISEASE?

1294
00:50:42,044 --> 00:50:43,345
IS THE FUTURE JUST ANYTHING TO

1295
00:50:43,345 --> 00:50:45,113
BE GOOD ENOUGH MOLECULAR

1296
00:50:45,113 --> 00:50:47,883
PROFILING THAT THESE WILL BE

1297
00:50:47,883 --> 00:50:50,152
DIFFERENTIATED IN A MORE

1298
00:50:50,152 --> 00:50:55,023
MEANINGFUL WAY? 

1299
00:50:55,023 --> 00:50:55,524
>> VERY GOOD QUESTION.

1300
00:50:55,524 --> 00:50:58,560
BECAUSE I ONLY SEE THESE, 70% OF

1301
00:50:58,560 --> 00:51:01,997
MY PATIENTS ARE T-CELL AND WE DO

1302
00:51:01,997 --> 00:51:08,270
HAVE OBVIOUSLY B-CELL, AND OTHER

1303
00:51:08,270 --> 00:51:10,839
CUTANEOUS CELLS, MFNS IS THE

1304
00:51:10,839 --> 00:51:14,176
MOST COMMON, SO WE HAVE THE CD30

1305
00:51:14,176 --> 00:51:17,112
PHOSPHATE, AND THE CYTOTOXIC

1306
00:51:17,112 --> 00:51:20,048
T-CELL LYMPHOMAS, A LOT OF

1307
00:51:20,048 --> 00:51:23,518
DIFFERENT TYPES, BUT WITHIN MF

1308
00:51:23,518 --> 00:51:25,353
AND SEZARY, IT'S SO

1309
00:51:25,353 --> 00:51:27,022
HETEROGENIUS, SO, I ONLY STUDY

1310
00:51:27,022 --> 00:51:30,692
THIS DEC, AND IT'S CONSOUPING MY

1311
00:51:30,692 --> 00:51:32,060
CAREER AND MY LYMPHOMA

1312
00:51:32,060 --> 00:51:33,328
COLLEAGUES ARE GOING, LIKE, YOU

1313
00:51:33,328 --> 00:51:37,365
ONLY DO THAT, WHY CAN'T YOU DO

1314
00:51:37,365 --> 00:51:39,000
MORE, THE THING IS LIKE YOU

1315
00:51:39,000 --> 00:51:41,336
SAID, EACH PATIENT IS SO

1316
00:51:41,336 --> 00:51:42,738
HETEROGENIUS, IT'S LIKE TREATING

1317
00:51:42,738 --> 00:51:46,074
MULTIPLE DIFFERENT DISEASES AND

1318
00:51:46,074 --> 00:51:46,742
LEARNING ABOUT IT.

1319
00:51:46,742 --> 00:51:48,276
SO IN TERMS OF IS IT ALL 1

1320
00:51:48,276 --> 00:51:49,678
DISEASE, I THINK IT DEPENDS ON

1321
00:51:49,678 --> 00:51:52,914
HOW YOU DEFINE IT, OBVIOUSLY WE

1322
00:51:52,914 --> 00:51:54,549
DEFINE CURRENTLY THE MF BECAUSE

1323
00:51:54,549 --> 00:51:58,220
THEY HAVE A SIMILAR SHARED

1324
00:51:58,220 --> 00:51:59,121
CLINICAL PRESENTATION WITH THE

1325
00:51:59,121 --> 00:52:00,889
PATCH BACK TUMOR AND THEY HAVE A

1326
00:52:00,889 --> 00:52:01,723
MIX OF IT.

1327
00:52:01,723 --> 00:52:06,428
THEY ARE ALL CONNECTED, PATIENTS

1328
00:52:06,428 --> 00:52:08,396
ARE PATCH LIKE TUMORS AND

1329
00:52:08,396 --> 00:52:11,700
SOMETIMES VICE VERSA, AND IN THE

1330
00:52:11,700 --> 00:52:13,568
SPECTRUM OF THEIR PATH, YOU CAN

1331
00:52:13,568 --> 00:52:15,337
CLEAR THE TUMOR AND TUMORS THEN

1332
00:52:15,337 --> 00:52:16,404
THEY'RE WITH PATCHES ONLY, THEN

1333
00:52:16,404 --> 00:52:17,572
YOU HAVE TO USE THE TREATMENTS

1334
00:52:17,572 --> 00:52:20,642
THAT WORK WITH THE PATCHES, SO

1335
00:52:20,642 --> 00:52:22,944
IT'S VERY DYNAMIC, PLASTIC,

1336
00:52:22,944 --> 00:52:23,612
PLACENTASISSITY, SO THEY'RE

1337
00:52:23,612 --> 00:52:25,714
INTERRELATED SO WE DON'T WANT TO

1338
00:52:25,714 --> 00:52:27,115
LIKE SEPARATE IT, I'M USUALLY A

1339
00:52:27,115 --> 00:52:29,084
LUMPER SO I DON'T WANT TO LIKE

1340
00:52:29,084 --> 00:52:31,686
SEPARATE THEM ALL OUT, BUT THE

1341
00:52:31,686 --> 00:52:32,254
LEUKEMIC DISEASE, AGAIN,

1342
00:52:32,254 --> 00:52:33,221
OBVIOUSLY IT MAKES YOU WANT TO

1343
00:52:33,221 --> 00:52:36,992
BE IN THE BLOOD MORE THAN THE

1344
00:52:36,992 --> 00:52:37,959
SKIN, WE HAVE TO UNDERSTAND

1345
00:52:37,959 --> 00:52:41,797
THESE BETTER BUT THEN IF YOU SAW

1346
00:52:41,797 --> 00:52:44,065
MY PATIENT, IN THE SAME PATIENT

1347
00:52:44,065 --> 00:52:45,467
IT'S DYNAMIC SO THERE WERE LUNG

1348
00:52:45,467 --> 00:52:49,971
CANCER  LUNG

1349
00:52:49,971 --> 00:52:51,239
CANCER--LEUKEMIC AND THEN THEY

1350
00:52:51,239 --> 00:52:52,507
LOOKED LIKE SKIN CANCER

1351
00:52:52,507 --> 00:52:52,908
PATIENTS.

1352
00:52:52,908 --> 00:52:54,843
SO I WANT TO CALL IT LIKE A

1353
00:52:54,843 --> 00:52:56,244
SPECTRUM OF DISEASE, BUT MAYBE

1354
00:52:56,244 --> 00:52:57,879
THE MOLECULAR PLATFORMS IN THE

1355
00:52:57,879 --> 00:52:58,146
FUTURE?

1356
00:52:58,146 --> 00:53:01,216
I WOULD LOVE TO GET TO A POINT,

1357
00:53:01,216 --> 00:53:03,251
IT'S LIKE CLL, AND YOU HAVE THIS

1358
00:53:03,251 --> 00:53:04,619
MUTATION YOU TREATED THIS WAY

1359
00:53:04,619 --> 00:53:05,654
AND WE NEED TO GET THERE BUT

1360
00:53:05,654 --> 00:53:07,689
IT'S NOT GOING TO BE THAT EASY

1361
00:53:07,689 --> 00:53:10,826
BECAUSE AGAIN, WE DON'T HAVE

1362
00:53:10,826 --> 00:53:13,595
VERY COMMON RECURRENT GENETIC,

1363
00:53:13,595 --> 00:53:15,230
YOU KNOW ABNORMALITIES IN A LOT

1364
00:53:15,230 --> 00:53:17,032
OF THESE PATIENTS, BUT I WOULD

1365
00:53:17,032 --> 00:53:19,668
LIKE TO GROUP THEM, BUT IT'S

1366
00:53:19,668 --> 00:53:24,840
VERY JUST DIVERSE HETEROGENIUS.

1367
00:53:24,840 --> 00:53:31,146
>> I WAS INTERESTED IN THE
JACK

1368
00:53:31,146 --> 00:53:33,548
STORY AND JACK INHIBITORS ARE

1369
00:53:33,548 --> 00:53:35,050
WIDE SPREAD USE HERE FOR MANY,

1370
00:53:35,050 --> 00:53:36,484
MANY THINGS AS CAN YOU IMAGINE

1371
00:53:36,484 --> 00:53:38,820
AND IF YOU HAD ANY EXPERIENCE

1372
00:53:38,820 --> 00:53:40,589
WITH LYMPHOMAS DEVELOPING ON

1373
00:53:40,589 --> 00:53:41,456
JACK INHIBITOR THERAPY AND YOUR

1374
00:53:41,456 --> 00:53:46,194
THOUGHTS ON HOW THAT FITS.

1375
00:53:46,194 --> 00:53:47,896
>> ANOTHER VERY GOOD POINT
WITH

1376
00:53:47,896 --> 00:53:52,133
THE EXPLOSION AND THE ATOPIC

1377
00:53:52,133 --> 00:53:53,435
DERM PSORIASIS, AND BIOLOGICS

1378
00:53:53,435 --> 00:53:54,502
AND IT'S A DIFFERENT THING WHEN

1379
00:53:54,502 --> 00:53:56,037
YOU HAVE OUR PATIENT THAT

1380
00:53:56,037 --> 00:53:59,441
PATIENT, THAT PATIENT HAD A VERY

1381
00:53:59,441 --> 00:54:00,442
SPECIFIC TUMOR MUTATION, CANCER

1382
00:54:00,442 --> 00:54:02,744
MUTATION, THAT WE THINK IS LIKE

1383
00:54:02,744 --> 00:54:06,014
A DRIVING, DRIVER OF THAT

1384
00:54:06,014 --> 00:54:07,182
CANCER, BUT LET'S SAY YOU DON'T

1385
00:54:07,182 --> 00:54:10,552
KNOW THAT AND THAT'S WHY I DON'T

1386
00:54:10,552 --> 00:54:12,020
LIKE USING THESE JACK INHIBITORS

1387
00:54:12,020 --> 00:54:17,025
OR ANY OF THAT, ESPECIALLY WHEN

1388
00:54:17,025 --> 00:54:18,760
YOU DON'T KNOW WHAT DRIVER OF

1389
00:54:18,760 --> 00:54:23,465
THE CANCER IS, BUT IN THE ATOPIC

1390
00:54:23,465 --> 00:54:24,499
DERMA PSORIASIS, LET'S SAY YOU

1391
00:54:24,499 --> 00:54:26,768
USE IT AND THE PATIENT NEVER

1392
00:54:26,768 --> 00:54:27,402
EVEN HAD DERMA TITIS.

1393
00:54:27,402 --> 00:54:30,005
SO WHAT I THINK IS THAT YOU

1394
00:54:30,005 --> 00:54:31,673
THINK THE PATIENT HAS ETOPPIC

1395
00:54:31,673 --> 00:54:35,744
DERM, BUT THEY LOOK, CTCL LOOKS

1396
00:54:35,744 --> 00:54:37,178
LIKE ATOPIC DERM, SO YOU DIDN'T

1397
00:54:37,178 --> 00:54:39,714
DO A DEEP DIVE INTO THE

1398
00:54:39,714 --> 00:54:41,149
DIAGNOSIS, CLONALITY AND MAYBE

1399
00:54:41,149 --> 00:54:42,984
COULD FIND THE CLONE BUT THEY

1400
00:54:42,984 --> 00:54:47,088
WERE  EVOLVING LYMPHOMA, SO NOW

1401
00:54:47,088 --> 00:54:50,058
YOU'RE LIKE NOT GETTING TO THE

1402
00:54:50,058 --> 00:54:50,926
FUNDAMENTAL DRIVER MUTATION OF

1403
00:54:50,926 --> 00:54:53,528
THE CANCER PATIENT THAT YOU

1404
00:54:53,528 --> 00:54:55,263
THINK, IT'S DERMATITIS BUT IT'S

1405
00:54:55,263 --> 00:54:58,867
LIKE EVOLVING CANCER BUT YOU'RE

1406
00:54:58,867 --> 00:54:59,734
JUST IMMUNE SUPPRESSING THEM IN

1407
00:54:59,734 --> 00:55:01,202
THAT CASE, I THINK YOU'RE

1408
00:55:01,202 --> 00:55:02,137
GETTING INTO SOME TROUBLE.

1409
00:55:02,137 --> 00:55:05,707
SO NOW WITH THE JACK INHIBITORS

1410
00:55:05,707 --> 00:55:07,709
AND ATOPIC DERM, AS HAPPENED IN

1411
00:55:07,709 --> 00:55:09,044
THE [INDISCERNIBLE] TRIALS WHERE

1412
00:55:09,044 --> 00:55:12,013
PEOPLE WERE NOT DIAGNOSTICALLY

1413
00:55:12,013 --> 00:55:13,348
VERY DISCIPLINARY FIN TIFF, I

1414
00:55:13,348 --> 00:55:14,449
THINK YOU WILL GET INTO SOME

1415
00:55:14,449 --> 00:55:17,118
CASES WHERE IT WAS NEVER ATOPIC

1416
00:55:17,118 --> 00:55:18,186
DERMA TITIS TO BEGIN WITH AND

1417
00:55:18,186 --> 00:55:24,092
THEN YOU WILL SEE MORE OF THE

1418
00:55:24,092 --> 00:55:24,359
UPMASKING.

1419
00:55:24,359 --> 00:55:26,494
WHEREAS IN SOME CASES JUST THE

1420
00:55:26,494 --> 00:55:27,228
CHRONIC SKIN DISEASE LIKE

1421
00:55:27,228 --> 00:55:29,364
WOUNDING, YOU KNOW CAUSES

1422
00:55:29,364 --> 00:55:29,831
GENETIC EVENTS.

1423
00:55:29,831 --> 00:55:33,468
SO WITH TIME YOU DID START WITH

1424
00:55:33,468 --> 00:55:34,836
A DERMATITIS, AND THEN WITH TIME

1425
00:55:34,836 --> 00:55:37,405
THEY EVOLVED AND HAD MUTATIONS

1426
00:55:37,405 --> 00:55:39,207
AND THEN, YOU KEEP HITTING THEM

1427
00:55:39,207 --> 00:55:40,976
WITH AN IMMUNE SUPPRESSIVE AGENT

1428
00:55:40,976 --> 00:55:42,844
AND IT WASN'T THE DRIVER OF THAT

1429
00:55:42,844 --> 00:55:44,379
CANCER, THEN YOU'RE GOING TO GET

1430
00:55:44,379 --> 00:55:46,715
INTO PROBLEMS, SO I THINK WE'RE

1431
00:55:46,715 --> 00:55:47,882
GOING TO--TIME WILL TELL BUT I

1432
00:55:47,882 --> 00:55:51,186
DO THINK WE NEED TO HAVE SOME

1433
00:55:51,186 --> 00:55:52,354
CAUTIONARY WORD OUT THERE THAT

1434
00:55:52,354 --> 00:55:56,858
MAKE SURE YOU HAVE A CORRECT

1435
00:55:56,858 --> 00:56:02,097
DIAGNOSIS, AND BE ENTHUSIASTS OF

1436
00:56:02,097 --> 00:56:03,298
THE BIOLAGIC USERS.

1437
00:56:03,298 --> 00:56:03,665
>> THANK YOU.

1438
00:56:03,665 --> 00:56:04,966
>> WE DO HAVE A QUESTION
THAT

1439
00:56:04,966 --> 00:56:07,535
CAME IN VIA THE VIDEOCAST

1440
00:56:07,535 --> 00:56:08,837
WEBSITE, THERE ARE A NUMBER OF

1441
00:56:08,837 --> 00:56:11,106
QUESTIONS BUT THE FIRST WAS

1442
00:56:11,106 --> 00:56:14,409
REGARDING YOUR EXAMPLE OF PEMBRO

1443
00:56:14,409 --> 00:56:15,310
WITH RAIDERIATION, YOUR THOUGHTS

1444
00:56:15,310 --> 00:56:17,045
ON WHETHER OR NOT THERE'S A

1445
00:56:17,045 --> 00:56:20,615
SYNERGY WITH SPECIFIC TARGETED

1446
00:56:20,615 --> 00:56:22,550
THERAPIES AND RADIATION?

1447
00:56:22,550 --> 00:56:26,221
>> YES, AND WE'RE VERY
INTO

1448
00:56:26,221 --> 00:56:27,956
RADIO IMMUNOTHERAPY, THAT

1449
00:56:27,956 --> 00:56:29,624
SYNERGY BECAUSE OBVIOUSLY IT'S

1450
00:56:29,624 --> 00:56:33,561
RADIATION IS A VERY IMPORTANT

1451
00:56:33,561 --> 00:56:35,463
DEBULKING TREATMENT, IT CAN

1452
00:56:35,463 --> 00:56:37,332
UNMASK ANTIGENS, WE LOVE IT AND

1453
00:56:37,332 --> 00:56:39,200
COMBINING WITH IMMUNE THERAPY

1454
00:56:39,200 --> 00:56:39,868
WOULD BE GREAT.

1455
00:56:39,868 --> 00:56:44,272
WE DO THINK THERE'S SYNERGY WITH

1456
00:56:44,272 --> 00:56:45,607
PEMBRO, WITH RADIATIONS WE WOULD

1457
00:56:45,607 --> 00:56:47,942
LIKE TO COMBINE, TOTAL SKIN IS

1458
00:56:47,942 --> 00:56:49,878
GREAT BUT EVEN LOCAL RADIATION,

1459
00:56:49,878 --> 00:56:52,614
DO WE HAVE SCIENTIFIC DATA?

1460
00:56:52,614 --> 00:56:55,350
WE'RE NOT THERE BUT CLINICAL

1461
00:56:55,350 --> 00:56:56,985
SYNERGY WE'RE SEEING.

1462
00:56:56,985 --> 00:56:58,286
SO CLINICAL SYNERGY--EACH IF YOU

1463
00:56:58,286 --> 00:57:00,021
HAVE SCIENTIFIC DATA THEY MAY

1464
00:57:00,021 --> 00:57:02,323
NEVER HAVE CLINICAL SYNERGY,

1465
00:57:02,323 --> 00:57:09,264
VICE VERSA, BUT WE DO SEE THAT,

1466
00:57:09,264 --> 00:57:10,331
AND THE IT WORKING.

1467
00:57:10,331 --> 00:57:13,768
WE HAVE A PATIENT WHO IS WITH

1468
00:57:13,768 --> 00:57:20,141
SEZARY, AND WHO IS ON THE PEMBRO

1469
00:57:20,141 --> 00:57:22,310
TRIAL, BUT IT'S CLEAR, BUT SOME

1470
00:57:22,310 --> 00:57:26,681
STARTED COMING AND SOME BLOOD

1471
00:57:26,681 --> 00:57:29,117
STARTED TO MOLECULARLY RISING SO

1472
00:57:29,117 --> 00:57:31,820
WE DECIDED TOADA THE TOTAL

1473
00:57:31,820 --> 00:57:33,455
ELECTRON SCREENING SO ONCEEE

1474
00:57:33,455 --> 00:57:35,156
SHOULD THAT WE SHE HAD

1475
00:57:35,156 --> 00:57:37,058
REMISSION, WE GAVE VERY LOW

1476
00:57:37,058 --> 00:57:38,893
DOSE, BUT USING VERY LOW DOSE

1477
00:57:38,893 --> 00:57:41,396
FOR THE SKIN, WE HAD IMMUNE O

1478
00:57:41,396 --> 00:57:43,064
GENICMENTATION IN THAT PATIENT

1479
00:57:43,064 --> 00:57:47,569
CLINICALLY AND THEN, SHE HAD

1480
00:57:47,569 --> 00:57:48,870
LIKE SUSTAINED SUSTAINED CR, SO

1481
00:57:48,870 --> 00:57:50,672
IT'S IMPORTANT TO COMBINE THOSE

1482
00:57:50,672 --> 00:57:56,945
AND DO MORE EVALUATIONS.

1483
00:57:56,945 --> 00:57:57,946
>> ONE OF THE OTHER
QUESTIONS

1484
00:57:57,946 --> 00:58:00,081
THE PERSON HAD WAS IF YOU HAD

1485
00:58:00,081 --> 00:58:04,252
ANY THOUGHTS ABOUT CD70 AS A

1486
00:58:04,252 --> 00:58:07,088
THERAPEUTIC TARGET.

1487
00:58:07,088 --> 00:58:08,123
>> ALTHOUGH CD70 HAS BEEN
HIGHLY

1488
00:58:08,123 --> 00:58:10,425
EXPRESS INDEED A LOT OF CANCERS,

1489
00:58:10,425 --> 00:58:12,594
NORMAL CELLS, TOO, BUT IN T-CELL

1490
00:58:12,594 --> 00:58:18,333
LYMPHOMA IT'S HIGHLY EXPRESSED

1491
00:58:18,333 --> 00:58:20,001
AND SO, THERE'S CD70 TARGETED AS

1492
00:58:20,001 --> 00:58:23,438
A NAB O BODY OR CAR-T, I'M SURE,

1493
00:58:23,438 --> 00:58:26,474
MANY OF YOU MAY KNOW ABOUT CRSPR

1494
00:58:26,474 --> 00:58:29,177
THAT HAS DONE SOME GREAT EDITING

1495
00:58:29,177 --> 00:58:32,447
WORK OF THE GENE EDITING OF THE

1496
00:58:32,447 --> 00:58:36,451
CAR-T, TO MAKE IT EFFECTIVE

1497
00:58:36,451 --> 00:58:37,485
AGAINST T-CELL LYMPHOMA,

1498
00:58:37,485 --> 00:58:38,586
REDUCING THE FRACTURE SITE AND

1499
00:58:38,586 --> 00:58:41,156
HAVE MORE LASTING CAR-Ts, SO

1500
00:58:41,156 --> 00:58:43,424
CD70 IS A TARGET BECAUSE OF

1501
00:58:43,424 --> 00:58:44,058
THAT.

1502
00:58:44,058 --> 00:58:46,261
BECAUSE IT'S EXPRESSED, VERY

1503
00:58:46,261 --> 00:58:50,098
MUCH IN T-CELL LYMPHOMA AND CTCL

1504
00:58:50,098 --> 00:58:50,632
AS WELL.

1505
00:58:50,632 --> 00:58:56,137
>> AND MY LAST QUESTION,
I'M

1506
00:58:56,137 --> 00:58:57,405
CURIOUS YOUR OPINION WITH CHECK

1507
00:58:57,405 --> 00:58:59,207
POINT THERAPY AND SIDE EEIVETS,

1508
00:58:59,207 --> 00:59:03,044
IS IT WHAT WE SEE WITH MELANOMA

1509
00:59:03,044 --> 00:59:03,912
AND OTHER MALIGNANCIES?

1510
00:59:03,912 --> 00:59:06,481
>> YES, I DON'T THINK
THERE'S

1511
00:59:06,481 --> 00:59:08,082
ANY SIGNIFICANT DIFFERENCE, BUT,

1512
00:59:08,082 --> 00:59:10,051
YOU KNOW WE DON'T--WE HAVE NOT

1513
00:59:10,051 --> 00:59:16,624
SEEN TOO MUCH AND WE DON'T WORRY

1514
00:59:16,624 --> 00:59:19,861
TOO MUCH ABOUT LONG-TERM

1515
00:59:19,861 --> 00:59:20,895
[INDISCERNIBLE] BECAUSE I WISH

1516
00:59:20,895 --> 00:59:22,230
THINGS WORKED THAT WELL IN ALL

1517
00:59:22,230 --> 00:59:23,898
PARENTS FOR A DURABLE PERIOD OF

1518
00:59:23,898 --> 00:59:27,068
TIME BUT IT DOESN'T, SO, BUT I

1519
00:59:27,068 --> 00:59:28,603
THINK THERE'S NO DIFFERENCE IN

1520
00:59:28,603 --> 00:59:29,904
THE SIDE CENTER FOR EXCELLENCE

1521
00:59:29,904 --> 00:59:32,106
ON AGING PROFILE.

1522
00:59:32,106 --> 00:59:32,707
--SIDE EFFECT PROFILE.

1523
00:59:32,707 --> 00:59:34,709
>> THANK YOU AGAIN FOR A

1524
00:59:34,709 --> 00:59:36,311
WONDERFUL TALK, A COMPLEX TOPIC

1525
00:59:36,311 --> 00:59:37,478
AND IN THE INTEREST OF TIME I

1526
00:59:37,478 --> 00:59:39,147
THINK WE WILL END THERE AND

1527
00:59:39,147 --> 00:59:45,720
THANK YOU SO MUCH FOR YOUR TIME 

1528
00:59:45,720 --> 00:59:48,957
>> THANK YOU DR. COWEN FOR
THE

1529
00:59:48,957 --> 00:59:50,358
INVITATION AND HOPEFULLY IT WAS

1530
00:59:50,358 --> 00:59:51,960
BENEFICIAL FOR THE LARGER

1531
00:59:51,960 --> 00:59:56,564
AUDIENCE. 

1532
00:59:56,564 --> 00:59:57,365
>> THOWCH.

1533
00:59:57,365 --> 01:00:07,642
>> THANK YOU.