Pediatric Leukemia & Acute Lymphocytic Leukemia

Transcript

• 00:00So the abstracts that are selected were
• 00:03chosen by the speakers because they are
• 00:06the most clinically relevant and they are
• 00:09grouped in areas of clinical unmet need.
• 00:12Of course that doesn't mean that other
• 00:15abstracts that have been presented in
• 00:18the meeting or are as good or important,
• 00:21but you have to choose basically for this
• 00:24type of sessions important to remember.
• 00:27Again, many of the ash presentations.
• 00:31Basically are focused on preliminary
• 00:33data and subsequently some of those
• 00:36results might be modified and
• 00:38they are still not peer reviewed,
• 00:40so this is important to keep up in mind as we
• 00:45think about the data that will be presented.
• 00:50That there will be a recording of
• 00:52this session and all the sessions.
• 00:54This will be available and accessible as
• 00:57in during material in addition to the
• 00:59slides and at the end of the entire series,
• 01:02the six sessions you'll be able
• 01:04to claim your CME credit.
• 01:05For those of you who wants to claim it.
• 01:08After you answer a brief evaluation
• 01:10and some feedback about how we can
• 01:13improve the format of of the series.
• 01:17So today it's a pleasure
• 01:19to introduce the speakers.
• 01:21Sorry, there's a typo here is clearly
• 01:23this is not on my Lloyd update.
• 01:26It's the pediatric leukemia updates.
• 01:28So Doctor but also full start by.
• 01:32Talking to us about major
• 01:33updates from the meeting about
• 01:35Accutane for blastic leukemia.
• 01:38Then Doctor Nina Kadan Lotic will
• 01:40update us and I think some of the
• 01:43most important updates from the
• 01:45ASH meeting on pediatric leukemias,
• 01:48including LL, of course,
• 01:50and then at the end, Dr.
• 01:52Nikita Shah will present to us or
• 01:55will moderate the Q&A session for any
• 01:58questions that will arise about the
• 02:01talks that will be presented our the.
• 02:04Abstractly presented,
• 02:05but also about any other additional
• 02:07questions about pediatric hematology,
• 02:09and in general so we look forward
• 02:12to a very exciting discussion,
• 02:15and I would like to start by
• 02:18introducing Doctor Nikolai Bodos.
• 02:20If our associate professor of medicine,
• 02:23here in the hematologist auction,
• 02:25who focuses on Accutane for blastic leukemia.
• 02:36Nicola, you're on mute.
• 02:44He would go so almost there next.
• 02:48Let me see. Looking for
• 02:51my PowerPoint here ago.
• 02:56Right, and do you see a single screen?
• 03:01Yep OK alright. So hold on one second let
• 03:05me just get to the beginning of all this.
• 03:10Not sure why this happened this way.
• 03:15So I would like to start
• 03:17from a brief introduction,
• 03:18so this are my disclosures.
• 03:20And we will be talking about
• 03:23acute lymphoblastic leukemia,
• 03:24which is further abbreviated as a LL.
• 03:28This is still the disease of the young
• 03:30and I represent adult hematology here,
• 03:32so Nina will be talking to what's happening
• 03:35in this field in pediatric hematology.
• 03:37And we certainly learned a lot over the
• 03:39last years from our pediatric colleagues,
• 03:42so this shows you that about 6000 patients
• 03:44are diagnosed with acute lymphoblastic
• 03:46leukemia per year in the United States,
• 03:49and only about 2000 of
• 03:50them are actually adults.
• 03:52Median age of diagnosis, as you can see,
• 03:54is around 9 years old and about
• 03:571500 deaths per year, most of them.
• 04:00Are adults.
• 04:02So these survival remains very
• 04:03different between pediatric LL
• 04:05patients and adult male patients,
• 04:06and you can see 5 year old survival
• 04:09is about 90% and children and
• 04:12still half of that in adults.
• 04:14So we're excited to have approvals
• 04:17for newbs CLL therapies.
• 04:19You can call them immuno therapies.
• 04:22This includes approval of
• 04:24Blinatumomab in 2017 by FDA.
• 04:26It's a bispecific T cell engager
• 04:29attacking CD 19 positive B cells
• 04:32including the lymphoblasts.
• 04:33Also in 2017 there was an approval notice
• 04:37amalgamation which is antibody drag Queen.
• 04:40You get attacking CD 22 on again
• 04:43B cells and finally approval of.
• 04:46It is a jungle occlusal.
• 04:49The car T cell therapy for younger
• 04:51patients with relapsed refractory disease.
• 04:54Again,
• 04:54attacking CD 19 cells on view lymphoblasts.
• 04:57This is for patients who are
• 05:00younger than 26 or younger,
• 05:02so the mechanism of action is bluna.
• 05:05Tumors represent on this slide is bite.
• 05:08Bispecific T cell engager,
• 05:10which attaches cytotoxic T
• 05:11cells to tumor cells.
• 05:13Through a CD 19 and by means of
• 05:16this attachment increases the.
• 05:19A pop ptosis of this tumor cells?
• 05:21So the studies which put this on
• 05:24the map and make it available to
• 05:27us are tower phase three study,
• 05:29which looked at Glenna to mob
• 05:31in relapsed refractory disease
• 05:33against conventional chemotherapy.
• 05:35And as you can see,
• 05:37there was a survival difference
• 05:39of 7.7 versus four months,
• 05:41which was statistically significant.
• 05:43Response rate was 44%,
• 05:44with 76% achieving mean negative,
• 05:46minimal residual disease.
• 05:48So this is all control study
• 05:50also blinatumomab it's an.
• 05:52It's a phase two study single arm
• 05:54looking at BLT amount for Peach paused,
• 05:57available patients and again you can
• 05:59see that the survival here for this
• 06:02patients with relapsed refractory pH.
• 06:03Posted bail is about 7.1 months with
• 06:06response rate of 36% among those patients.
• 06:08So the drug is approved for both
• 06:11relapse refractory pH positive
• 06:12and pH negative B cell L patients.
• 06:15The next drug is in its mother's advice
• 06:18and its antibody drag Queen you get.
• 06:20Which brings Felicia my son to
• 06:23the B cell positive for CD 22.
• 06:25After internalization,
• 06:26the drug is released inside the cell
• 06:29and code goes to the nucleus to cause
• 06:32cause DNA damage in a pop ptosis.
• 06:35Some of the drugs you can see
• 06:37can be flexed
• 06:38and circulating blood causing the
• 06:40main side effect of this medication
• 06:43in occlusive disease and deliver.
• 06:46So this study we as a Cancer Center
• 06:49participated in and contributed patients
• 06:51to innovate phase three study looked
• 06:53at the data some up again and relapse
• 06:56refractory B cell L patients including
• 06:58Peach posed accomplish negative
• 07:00and showed improved survival when
• 07:02compared to standard therapy group.
• 07:03So the median overall survival was 7.7
• 07:06versus 6.7 months and response rate was
• 07:09kind of double of what we see in Blender.
• 07:12Two map studies about 80% again
• 07:14with most of the patients 17%.
• 07:16Accomplishing negative minimal
• 07:18residual disease status.
• 07:20So today I'm going to talk about four
• 07:24studies and basically all of them.
• 07:28Are about adult patients with
• 07:30the introduction of drugs,
• 07:31which I used in relapse refractory setting
• 07:34in the frontline therapy for some of them.
• 07:37So we are trying to capitalize on the
• 07:41accomplishment and approval of this
• 07:43drugs and try to move them up front
• 07:46to get our patients to have better
• 07:49responses and ultimately survival.
• 07:50So the studies are grouped based
• 07:53on our approach to management of
• 07:55these patients and refers to wall.
• 07:58Look at the patient age and
• 08:00then Peach chromosome status,
• 08:02pH positive and pH.
• 08:04Negative patients are treated quite
• 08:06differently as you will see.
• 08:07So the first study is from MD Anderson
• 08:11Cancer Center and I would like to thank
• 08:14all of the presenting authors who gave
• 08:17me their slides to share with you today.
• 08:20So the first study is about pH,
• 08:23negative B cell L adults who were treated
• 08:26with Hyper Civitan sequential blinatumomab.
• 08:29And again, the speech negative patients.
• 08:30So let's have a look at the results of
• 08:33this phase two study from MD Anderson.
• 08:35So the primary endpoint of the study was
• 08:37relapse free survival secondary endpoints.
• 08:39You can look at here including overall
• 08:42response rate and MRD negativity rate.
• 08:44So this you are newly
• 08:46diagnosed patients with pH,
• 08:47negative B cell,
• 08:48LL patients could receive one cycle
• 08:50induction chemotherapy prior to enrollment.
• 08:52Of course they have to get to MD Anderson
• 08:55from elsewhere where they treated.
• 08:58So that's why they kind of broaden
• 09:00the inclusion criteria this way.
• 09:02Interestingly,
• 09:02they included patients age 14 and older,
• 09:05so this is usually going in the
• 09:07territory where Nina treats patients,
• 09:10so they allowed enrollment of younger
• 09:12patients on the study this patients.
• 09:15Have to be eligible for intensive
• 09:17chemotherapy.
• 09:18Equal Performance status of three
• 09:20or less adequate organ function
• 09:22and no significant CNS involvement.
• 09:24So CNS patients patient was
• 09:26seen as leukemia were excluded,
• 09:28so this is the schema of the study.
• 09:32You can see this is 4 cycles
• 09:34of hyper seaward, part A&B,
• 09:37with addition of Rituxan two patients for CD,
• 09:4020 positive or over to map another
• 09:43CD 20 antibody.
• 09:44As well as use of prophylactic it
• 09:47chemotherapy sectarian metrics 8 so
• 09:49after finishing this intensive phase,
• 09:51patients would go to blender two
• 09:53more phase where they would receive
• 09:556 four cycles of blinatumomab,
• 09:57four weeks on continuous infusion,
• 09:59two weeks off and.
• 10:00Go to maintenance phase which
• 10:02is actually 18 as opposed to 36
• 10:05months and the blender two map is
• 10:08incorporated between the cycles of pomp,
• 10:11chemotherapy and additional
• 10:123 cycles of blinatumomab.
• 10:13As you can see here.
• 10:16So these are the patients who were
• 10:18enrolled in the study, 38 patients.
• 10:21And as you can see the age difference.
• 10:24The H variance was between 17 and 59.
• 10:28The patients about 32% of patients had.
• 10:31Adverse karyotype the pH like
• 10:33positive patients were 19% as
• 10:35defined by presence of CRLF 21.
• 10:38Flow cytometry testing,
• 10:39and 27% of patients get TP 53 mutation.
• 10:43So this is one of the secondary points
• 10:46response rates CR after induction was
• 10:49accomplished in 81% of patients and then yes,
• 10:52you know they preceded with Blender
• 10:55two Mob and at the end of 32 patients
• 10:59accomplished a CR and MRD,
• 11:01negativity was 71%.
• 11:02After induction and 97% at anytime
• 11:05during the study,
• 11:06early mortality was at 0.
• 11:09So.
• 11:09I relapse free.
• 11:11Survival was not one of the endpoints
• 11:14of the study, and as you can see,
• 11:17relapse free survival at two years is 71%.
• 11:20At one year,
• 11:2180% overall survival was at two years of 80%,
• 11:24so it's pretty impressive numbers for
• 11:27patients for adults with B cell LL.
• 11:29Of course you know this particular group
• 11:33included younger patients 17 and older.
• 11:35So this is comparing the results
• 11:37of current study in blue with
• 11:40another study done in the same
• 11:43institution earlier hyper.
• 11:44See what with over to Mumbai think
• 11:4760 plus patient 69 patients and
• 11:49you can see that both studies show
• 11:52comperable to overall survival,
• 11:55but the plateau of no mortality
• 11:57after two years for the current
• 12:00study is very encouraging.
• 12:02So the side effects specifically
• 12:04adverse events of interest.
• 12:06Related to Blender two map
• 12:08highlighted in yellow side,
• 12:09The kind Release syndrome Grade 3 four
• 12:13was only seen in one patient and.
• 12:16It in your logical amounts were
• 12:19seen in 13% of patients.
• 12:21One patient,
• 12:22discontinued blended home up due to toxicity.
• 12:25It was great to encephalopathy and dysphasia,
• 12:28so the conclusion of this
• 12:30presentation is here.
• 12:31Hyper Squad with Sequential
• 12:34Blinatumomab is highly effective.
• 12:36Frontline therapy for pH negative deal
• 12:38adults, MRD rate was 97% year old,
• 12:41survival was 80%.
• 12:42There are no relapses beyond two years.
• 12:45There was low rate of grade three
• 12:47adverse events related to blinatumomab
• 12:49and at this time protocol is amended
• 12:52and now includes in autism observation.
• 12:54In addition to Blender tomorrow
• 12:57for frontline management of this
• 12:59group of patients. So the 2nd.
• 13:04Study or two studies.
• 13:05I would like to talk about our about
• 13:07older adults and the definition
• 13:09of all the adults in BLL world is
• 13:12different in different places.
• 13:13The first study again from this
• 13:15study is actually from Germany.
• 13:17German leukemia group and you know
• 13:19their definition of older adult was
• 13:2155 and older and then there will be.
• 13:24I will present results of meaning
• 13:26high perceived within autism
• 13:27up with or without Minotaur map.
• 13:29Here the definition is age 60 and older.
• 13:32So let's start from the German study.
• 13:34So this is. Initial one phase two trial
• 13:37which looked at induction treatment
• 13:39with three cycles of inotuzumab instead
• 13:41of regular chemotherapy induction,
• 13:43followed by standard to consolidate if
• 13:45approach from Journal Leukemia Group,
• 13:47which as you can see, is reasonably intense.
• 13:50Includes a asparaginase administration.
• 13:52It looks like 3 times.
• 13:54Also for CD 20 positive patients
• 13:56there is rituximab and so on.
• 13:58So this consolidation requires admission.
• 14:00And then there is about you know half
• 14:03of 6 MP methotrexate maintenance.
• 14:06Uh, so. The results,
• 14:09which were presented included
• 14:11mostly 31 patients,
• 14:13those who received at least one
• 14:15cycle Organism up induction and
• 14:18could be assessed for remission.
• 14:20So the patient characteristics table
• 14:22shows that patients which were enrolled
• 14:26were between 56 and 80 years old and
• 14:29you can see that all of these patients
• 14:32obviously had CD 22 expression.
• 14:34Different density of
• 14:36expression is represented here.
• 14:38So, uh,
• 14:39the secondary point end point of
• 14:41the study was response rates,
• 14:43and you can see that out 31 patients
• 14:47they looked at 100% had response CRCR I.
• 14:50And now this actually, you know,
• 14:53for patients receive three cycles.
• 14:5684% so some of them have their early
• 14:59relapses and there are no early deaths
• 15:02and then MRD was accomplished in
• 15:0478% of patients with this strategy.
• 15:06So there were some haematological
• 15:08and molecular responses.
• 15:10As you can see total of three
• 15:12and allogeneic stem transplant in
• 15:14remission was provided to three of
• 15:17those patients and one patient went
• 15:19to transplant after relapse so only
• 15:22four patients were transplanted
• 15:23out of this 31. So this is.
• 15:26The primary endpoint is on the right
• 15:28event free survival at one year,
• 15:30so was 87%.
• 15:31So for all the group of patients
• 15:33is actually pretty good and then
• 15:35overall survival at one year was
• 15:37also 87% events were defined,
• 15:39it persisting one marrable us after two
• 15:41cycles went into some of relapse or death.
• 15:44So this is a side effects are in relation
• 15:46to inductions within a two zone map.
• 15:49As you can see after initial
• 15:51induction that are more cytopenias.
• 15:53But you know this kind of decreases
• 15:55overtime obviously and then
• 15:57the side effect of interest.
• 15:58Here adverse event of interest would
• 16:01be LFT abnormalities because we
• 16:03inclusive disease is one of those
• 16:04things we watch for and then some of
• 16:07treated patients and LFTS elevation
• 16:09were not common and no patients
• 16:11had been occlusive disease.
• 16:12Of course only four.
• 16:13Patients out of city one went to
• 16:16allogeneic stem cell transplant.
• 16:18The conclusion of the study in this
• 16:20map seems to be highly effective as
• 16:23monotherapy and using haematological
• 16:24remission in all patients with MRD
• 16:27accomplished in more than 70% of
• 16:29patients had acceptable toxicity.
• 16:30No early deaths observed.
• 16:33Novena occlusive disease.
• 16:34Promising survival 80% overall
• 16:36survival benefit survival at one
• 16:38year and finally another man has a
• 16:40great potential to become standard
• 16:41induction option in all the patients
• 16:43with newly diagnosed
• 16:44BLL. So we're not using this regiment at
• 16:47Yale, and I don't think it is frequently
• 16:50used in the United States, so we're kind
• 16:53of more interested in high perceived,
• 16:55which is of course the Backbone Regiment for
• 16:57MD Anderson Cancer Center and many hyper.
• 17:00See what is something we used
• 17:02in some patients over years?
• 17:03Older patients with?
• 17:04We sell LL as well as T cell LL.
• 17:08So I'm going to share with you the
• 17:11results of this mini high perceived study,
• 17:14which added in a tumor band later
• 17:16one blinatumomab for management
• 17:18of all the patients with Vissel.
• 17:20So here, ages 60 or more before
• 17:23on status up to three.
• 17:25Adequate organ function ejection
• 17:27fraction should be more than 40%.
• 17:29So those reduced so-called meaning hyper
• 17:32see what consists of cyclophosphamide
• 17:34reduced by 50% dexamethasone,
• 17:36again reduced by 50%.
• 17:37There is no under cycling metrics
• 17:40take high dose metrics,
• 17:42a reduced by 75% anhydrous site,
• 17:44urban by 83%.
• 17:45So the inner tubes mob was added one day,
• 17:49three for the first 4 courses and
• 17:52rituximab was used as usual on D2 and
• 17:55eight with four CD 20 positive patients.
• 17:59Patients already also received it.
• 18:01Chemotherapy prophylaxis.
• 18:02So this is the schema of the study.
• 18:05You can see that there are the eight
• 18:08cycles with it chemotherapy administered
• 18:10during the first 4 as well as in ministered.
• 18:14As I specified overtime,
• 18:15the dozing off into some other Wolf
• 18:18first six patients higher dose than
• 18:21those was like lower dose than hide.
• 18:23Those was escalated,
• 18:25and then finally at the end they settled
• 18:28on a dose of 1.3 on cycle one and one.
• 18:32On Cycle 2,
• 18:33four.
• 18:33So the study was further modified
• 18:36after enrollment of 49 patients,
• 18:38and here you can see that
• 18:40four out of eight cycles,
• 18:42we only have 4 cycles of chemotherapy.
• 18:45Now Inotuzumab is given twice per cycle,
• 18:48and the dozing is here and blender to map.
• 18:524 cycles of blinatumomab I added in
• 18:55consolidation phase and maintenance
• 18:56was reduced from 36 months to
• 18:5918 months and now also includes
• 19:01four cycles of blinatumomab.
• 19:03So once again,
• 19:04this is starting from patient 50.
• 19:06An further total number of
• 19:08patients enrolled in this phase.
• 19:10Two trial with 70 patients.
• 19:11So 20 patients receive treatment this way.
• 19:14So this is characteristics of the patients.
• 19:16And as you can see that you know these
• 19:19are all the patients 6281 and there
• 19:22are 41% of them are 70 or older.
• 19:24The complex karyotype as well as other
• 19:27cytogenetic abnormalities which I
• 19:28usually associate with worse outcomes.
• 19:30I seen in at least a third of those patients.
• 19:34As well as quite a few patients
• 19:36had that Peach like disease and
• 19:39TP53 mutated disease,
• 19:40so the overall response rate was 98%.
• 19:43This includes CR,
• 19:45CR P&CRI and there were no early deaths.
• 19:48MRD response on the 21 I was observed in
• 19:5278% and overall in 96% of the patients.
• 19:55So the reason that why numbers
• 19:58are all different, there's been.
• 20:00Five patients were enrolled in
• 20:02CR on this
• 20:03study. This is the patients who received
• 20:05one cycle before they were enrolled
• 20:07because they have to make it to MD
• 20:09Anderson to start their treatment.
• 20:11So these are grade three adverse
• 20:12events and I just highlighted here
• 20:14being occlusive disease, which was
• 20:16seen only in nine percent of patients.
• 20:20So this is the complete remission duration,
• 20:23which at three years was 79%.
• 20:25That's the top blue line.
• 20:27The Red line is overall survival
• 20:29line 56% at three years.
• 20:31Once again these are all the patients
• 20:33and there's a pretty good results
• 20:35for this population of patients.
• 20:37So this slide highlights worse outcomes
• 20:40in patients who are 70 and older.
• 20:42This is the blue line.
• 20:44As you can see,
• 20:46three azerate three year survival rate
• 20:48was 65 for patients who are 60 to 69 and.
• 20:51Only 43 for patients 470 and older.
• 20:55So I think you can see that.
• 20:59Conclusions are based on this results.
• 21:01Overall response rate was 98%
• 21:03margin negativity in 96%.
• 21:04There were no early deaths.
• 21:063 SCR duration was 79.
• 21:08Overall survival of 56%.
• 21:10Best outcomes of course.
• 21:11In patients who are 60 to 69 and
• 21:14style studies now amended to
• 21:16eliminate chemotherapy for patients
• 21:18for 70 and older and older.
• 21:21A longer follow-up is of course
• 21:23needed to determine if a low dose
• 21:25fractionated into some oven blender
• 21:26to warm up will improve outcomes.
• 21:29So finally the last study is
• 21:31about pH positive DLL patients.
• 21:33Again, this is a study from MD Anderson Ann.
• 21:37Its interim results of the Phase 1
• 21:39two study of the Fanatic Phonetic
• 21:42locks and dexamethasone for
• 21:44patients with relapsed or refractory
• 21:46Philadelphia chromosome positive LL.
• 21:48So as you know,
• 21:49the never clocks is the drug
• 21:51which is currently approved for
• 21:53frontline treatment together with
• 21:55hyperventilating agents with FI LL
• 21:57also approved for treatment of CLL
• 21:59and so this is a BCL two inhibitor.
• 22:02So what is the logic of trying
• 22:05this drug in patients with DLL Now
• 22:08the outcomes of relapse refractory
• 22:10disease in Peach posted below poor.
• 22:13So the PACE trial showed that
• 22:15the native can induce responses
• 22:17and 40% of patients but one year
• 22:20progression free survival is only 8%.
• 22:23So pH positive LL is highly dependent
• 22:25on BCL two protein for its survival
• 22:28and that's why potentially there is
• 22:31a therapeutic role for phonetic lax.
• 22:34Preclinical studies also showed
• 22:35that platinum can cooperate with an
• 22:38attic locks and be synergistic in
• 22:40attacking Peach positive LL cells.
• 22:42So there is synergistic inhibition of growth.
• 22:45An induction of Opelousas,
• 22:46and perhaps the reason for it is
• 22:50inhibition of Lynn tires in Chinese by
• 22:53platinum and it increases beam and.
• 22:56Which prevents MCL one upregulation MCL.
• 22:58One is another anti up anti optic
• 23:01protein and usually in escape route
• 23:04when BCL two anti apoptosis is inhibited.
• 23:08So the results which were presented
• 23:10at ASH 2020 were results of the phase
• 23:12one of the study. Only nine patients.
• 23:14But you know,
• 23:15they are quite interesting and that's why
• 23:17I selected this for the discussion today.
• 23:20My so the point of Phase one studies of
• 23:22course to identify maximal tolerated
• 23:24dose of another class in combination
• 23:27with platinum and dexamethasone.
• 23:28There are secondary endpoint including
• 23:30CMR 8 Relapse free survival,
• 23:32overall survival and of course, safety.
• 23:34So.
• 23:35The patients who were included on
• 23:37the study
• 23:38where patients with relapsed
• 23:41refractory Peach positive LL with
• 23:43CML in lymphoid blah space and they
• 23:46have to be treated by at least one
• 23:50desireable TTI prior to the study.
• 23:52Age was 18 and older.
• 23:55Oclock performance status
• 23:56like in previous study.
• 23:58Adequate organ function nor uncontrolled
• 24:00active cardiovascular disease.
• 24:01Becausw Anatomy was known to have
• 24:03cardiovascular toxicity arterial occlusive,
• 24:05occlusive events,
• 24:05and no prior use of genetic lacks.
• 24:08So this is the schema of the study.
• 24:11Initially,
• 24:11patients were open at 9:45 for seven days,
• 24:14then the network locks ramp up together with
• 24:17dexamethasone for four days at 40 milligrams,
• 24:20so the phase one included
• 24:22ramping up to 400 milligrams,
• 24:24or 800 milligrams.
• 24:25So this were two.
• 24:27Those are some phonetic lacks which
• 24:29were accomplished in this study,
• 24:31so not new,
• 24:33but those was further reduced with.
• 24:37Haematological response to 30 milligrams
• 24:39and for patients with accomplished
• 24:41complete molecular response to.
• 24:4215 milligrams.
• 24:43To avoid arterial occlusive events and
• 24:46other side effects so as you can see,
• 24:49patients also received CNS prophylaxis
• 24:52and Rituxan if they were CD 20 positive.
• 24:55So this is the characteristic of this.
• 24:58Nine patients enrolled on this phase.
• 25:00One of the study you can see
• 25:03that the issue is 26 to 73.
• 25:05There were no patience with the
• 25:07with performance status of three,
• 25:09so half of the patients had T315I mutations.
• 25:12And as you can see it was very
• 25:15heavily pretreated group.
• 25:1717% order received platinum probably
• 25:18going to my treatment and 56% of patients
• 25:21and prior transplant in 67% of patients.
• 25:24So nine but very heavily pretreated
• 25:26patients with relapsed refractory disease.
• 25:29So we're not even look like
• 25:31Sundecks didn't cause any deal
• 25:32tease those limited toxicities.
• 25:34Maximal tolerated dose was not reached.
• 25:37Three patients were treated or
• 25:38magnetic locks 400 milligram those
• 25:40level one and six patients receive
• 25:43genetic lacks 800 milligrams and
• 25:45this was selected to be recommended.
• 25:47Phase two dose.
• 25:48There are no early mortality so
• 25:50the side effects are listed here.
• 25:52I think 1 interesting side effect in
• 25:55this storm Bolick event which occurred
• 25:57in one patient and was graded as Grade 3.
• 26:01Patient had DVT MP.
• 26:02There are patients who had
• 26:04great for Trump aside opinion,
• 26:07neutropenia but no febrile neutropenia.
• 26:09Not great four.
• 26:10So reasonably acceptable.
• 26:11Side effect profile for this
• 26:13heavily pretreated group of
• 26:15relapse refractory patients.
• 26:17So the response rate was 56%.
• 26:19Of course,
• 26:20it's five out of nine patients,
• 26:2344% of four now had CR and one had CR.
• 26:27I complete.
• 26:28Molecular response was accomplished.
• 26:31I'm on 4 out of nine patients and
• 26:33complete molecular response after
• 26:35first cycle was in three patients.
• 26:37One patient actually responded by
• 26:39decreasing blossom mirror from
• 26:4194 to 6% had neutrophil recovery
• 26:42in place with recovery,
• 26:44but was not counted as responded because
• 26:46Blacks were still about 5% in the marrow.
• 26:49So this is to highlight that phonetic
• 26:51likes those 800 milligram patients
• 26:53are the only patients who responded.
• 26:56None of the three patients
• 26:57who received an attic LAX
• 26:59at 400. Those responded, but five out of 6.
• 27:03Our patients in those two with 800
• 27:05milligrams of another class had response,
• 27:08so this is of course 9 patients.
• 27:10Potassium plus fanatical X
• 27:12one year old survival, 63%.
• 27:14Only two patients died and those were
• 27:16nonresponders they were not relapse patients.
• 27:19They did not respond to the magnet
• 27:21and Venetic lacks combination.
• 27:23And as you can see this
• 27:25is six months or less.
• 27:273 survival of 100% for five
• 27:29patients is reasonably reassuring.
• 27:31You once again it's a small phase one study.
• 27:35So in conclusion,
• 27:36this is oral regimen of banana
• 27:38phonetic likes and dexamethasone,
• 27:40and this looks like safe and
• 27:42effective in heavily pretreated,
• 27:43relapsed refractory Peach
• 27:45post available patients.
• 27:46Maximal tolerated dose was not reached,
• 27:48and those selected for phase two of
• 27:51this study is 800 MG CR CR rate was
• 27:5456 on CMR rate was 44% responses
• 27:57were observed across subgroups,
• 27:58but may be high in Veneta clocks.
• 28:01800 milligram daily Group estimated one
• 28:03year old survival 63% no relapses today.
• 28:06Correlative studies ongoing
• 28:07to better understand mechanism
• 28:09of response and resistance.
• 28:10So what do we do with yell
• 28:14to introduce this new drugs?
• 28:16Our two frontline management of
• 28:18our patients so we are opening this
• 28:20alliance study phase two trial
• 28:22overnight as a mob induction,
• 28:24followed by Glenna to map consolidation
• 28:26for patients with newly diagnosed
• 28:28or relapse refractory CD.
• 28:2922 points of DLL.
• 28:30I have to say that CD 19 and CD 22
• 28:34positivity is seen in more than
• 28:3690% of patients with SLE,
• 28:38so this cohort one includes patients
• 28:40older than 60 and older and we will
• 28:43be looking at event free survival,
• 28:45one event free survival.
• 28:46For this transplant in eligible
• 28:48patient group with newly diagnosed LL,
• 28:50the cohort two is for younger
• 28:53patients who have relapsed refractory
• 28:54disease and you know,
• 28:56of course this patients potentially can
• 28:58go to transplant if they have response.
• 29:01So this combination makes sense
• 29:02because of the existing vanity.
• 29:04Zoom up within occlusive disease post
• 29:06transplant and even without transplant.
• 29:08And that's why we would like to
• 29:10separate transplant by giving other
• 29:12treatments to this patients in between.
• 29:15Another modern transplant itself.
• 29:16So I would like to wrap it up at
• 29:21this point and next speaker doctor,
• 29:23Nina,
• 29:23Kate and Logic will be talking
• 29:26about pediatric AOL studies.
• 29:39You know, now you have to share your
• 29:41slides. I just unshared. Thank you.
• 29:57So thank you,
• 29:58I'm going to now shift the focus.
• 30:00Two childhood adolescent and young
• 30:03adult ELL and I'm including young
• 30:06adult because often the eligibility
• 30:08for our studies extend well into
• 30:11the 20s and sometimes older.
• 30:16So I'm going to focus most of my time on
• 30:21the 1st three abstracts. The first is our.
• 30:29Presented the results of our recently
• 30:32closed T cell lymphoblastic leukemia.
• 30:35Lymphoma study AALL 1231 in which Pertuzumab
• 30:38was studied and which cranial radiation
• 30:41was illuminated for 90% of patients.
• 30:44Next, I'm going to discuss results of
• 30:48using Blue Netuma map versus intensive
• 30:51chemo in children in high risk.
• 30:54First, relapse of B cell LL.
• 30:57Anne, and then I'm going to
• 31:01discuss some results regarding
• 31:03the prior use of Luna to mmap.
• 31:05As associated with karty outcomes.
• 31:11And then I'm going to shift and talk
• 31:14a bit about toxicity related to
• 31:17asparagine ease and maybe some of the
• 31:20factors associated with that toxicity.
• 31:28The first study is by the study chair,
• 31:31Doctor Teachey and I would like
• 31:34to also thank all the authors,
• 31:37investigators who slides I will present.
• 31:41And this is a ALL 1231.
• 31:44The reason that there is a
• 31:47T allow study even though.
• 31:51Three year event free survival
• 31:53approaches 90% is that T cell
• 31:56patients can't really be salvage.
• 31:58They have really. Abysmal outcomes.
• 32:02If they relapse, so the goal is to try
• 32:07to treat them up front as much as possible.
• 32:12So part is Amab is a proteasome inhibitor.
• 32:15It inhibits Dave teaching would call it
• 32:19the garbage can of the cell it inhibits.
• 32:23And is supposed to be pretty old.
• 32:26Zones are supposed to take
• 32:28care of waste from the cell.
• 32:30Inhibitors inhibit a number
• 32:31of the regulatory proteins,
• 32:33including NF KB,
• 32:34which is very important in T
• 32:36cell LL pathogenesis.
• 32:37It's been shown in relapse studies
• 32:40to be well tolerated and effective.
• 32:43So therefore it was the basis of this
• 32:46study and the Burtis amab is an upfront
• 32:50randomization randomization that starts
• 32:52an induction and those randomized
• 32:54get a total of eight doses of autism.
• 32:58The induction backbone changed for
• 33:00TLL compared to past studies in a
• 33:03nonrandomized way based on British
• 33:06data in which all patients get
• 33:08dexamethasone and two doses of peg.
• 33:11Asparagine, Ace, and then randomization.
• 33:13Is based on end of consolidation MRD.
• 33:18So one is classified as standard res
• 33:21intermediate risk or very high risk.
• 33:23Based on that and the backbone very
• 33:26slightly in terms of the intensive
• 33:29therapy based on risk status.
• 33:31The only group that gets radiation
• 33:34are the very high risk patients.
• 33:38For those who are seen as positive
• 33:41at diagnosis,
• 33:4190% of patients do not get
• 33:44radiation and this was decided.
• 33:46And that was one of the decisions
• 33:48for using dexamethasone induction
• 33:50because of the tire CNS penetration.
• 33:52There was a great goal in our
• 33:55group because of the high cure
• 33:58rates in the long term.
• 33:59Late effects to try to
• 34:01eliminate this this radiation.
• 34:06The T lymphoblastic lymphoma patients
• 34:08were also eligible for this study
• 34:11and their end of consolidation.
• 34:13MRD was based on Image Ng and I
• 34:15do want to emphasize patients 1
• 34:18to 30 years were eligible and we
• 34:21do have patients throughout that
• 34:24range so the majority are under 18.
• 34:30This time is expected to accrue 1400
• 34:33patients over 4.4 years, most powered
• 34:36for a 5% difference in four year EFS.
• 34:41However, it only enrolled 847 patients
• 34:44because went at that point to the
• 34:47results of the precursor study was
• 34:50available in that precursor study.
• 34:53AALL 0434 randomized to know Larabee
• 34:57nor not and was. Found to be.
• 35:03Very much an advantage to having
• 35:06allara been with event free survival.
• 35:10Advantage of about 5% and also
• 35:14at lower CNS recurrence rate.
• 35:17So that's the study was
• 35:20amended and closed early and.
• 35:24This is what was presented is the
• 35:27patients that were enrolled at 800
• 35:31approximately 800 patients and for TI.
• 35:34Don't know why this keeps moving for TLL,
• 35:39the. There was no difference.
• 35:43Arm A was the standard arm in ARM,
• 35:46B was upper to some arm.
• 35:48There was no difference in three
• 35:51year EFS or in three year.
• 35:53Overall survival by arm.
• 35:57But when one looked at it by risk group,
• 36:00those who were standard risk or who
• 36:03had the lowest MRD at the end of
• 36:06consolidation had a clear advantage
• 36:09of 92% versus 85% in three year FS.
• 36:12And there was a similar advantage
• 36:14in their intermediate risk.
• 36:16There was no advantage for purchase map,
• 36:18but in fact those who got burnt to the
• 36:22map did worse for very high risk TLL.
• 36:25Those who had high.
• 36:28End of consolidation burden or who were?
• 36:32Early relapse patients and this
• 36:35was statistically significant
• 36:36for unclear reasons,
• 36:38though it was speculated by the authors
• 36:42that this could relate to early toxicity.
• 36:46So in terms of the
• 36:49lymphoblastic lymphoma outcomes,
• 36:51there was an advantage.
• 36:53A statistically clear advantage
• 36:55of Virtusa ma'am,
• 36:57both for event free survival
• 37:00and overall survival.
• 37:02Up about 7 to 8%.
• 37:06We wanted to compare outcomes on 12th.
• 37:09Oh, that's what I did.
• 37:11OK, so the differences in
• 37:15induction therapy were remarkable
• 37:18in that there was a higher.
• 37:21So actually, going back with this
• 37:24and with this study truncated and
• 37:27with the recent AALLO 434 results,
• 37:30there were some opportunities to
• 37:33compare some strategies because
• 37:36the Miller Bing was not included
• 37:39in this current study because
• 37:42those results were not known and.
• 37:45Therefore, the. The.
• 37:51First thing that was examined was
• 37:54in those who got a little over 3,
• 37:57four, which would be known
• 37:59allara being an induction,
• 38:01but could get in conduct
• 38:03consolidation and then now I'm
• 38:05sorry this is end of induction, MRD.
• 38:08Those who got no LL Bean
• 38:11versus all comers for 1231.
• 38:13There was actually much higher MRD
• 38:16negativity in those in the later study.
• 38:19The 1231 that looked at Partism.
• 38:22Which is interesting because MRD
• 38:24says we typically think of as
• 38:26predictive of long-term outcomes,
• 38:28but not.
• 38:28It's not the only predictor in
• 38:31that kind of emphasizes that.
• 38:33The other thing that was really
• 38:35remarkable was that there was a
• 38:38lot more high grade toxicity in
• 38:40the PARTISM study compared to
• 38:42the previous Miller being study,
• 38:44and this is not clear why it's
• 38:46speculated to be due to the dexamethasone
• 38:49and the extra peg asparagine ease.
• 38:52So while the?
• 38:53Total number of events or
• 38:55toxic events were higher in
• 38:58the precursor study that 0434.
• 39:00There was a much higher rate of
• 39:03higher grade ones and they were
• 39:06due to infections predominantly
• 39:08and particularly fungal infections.
• 39:10The next thing that was examined was
• 39:13the cranial radiation, 'cause again,
• 39:16we had this opportunity to look in 043, four.
• 39:2090% of patients had cranial radiation.
• 39:23While in the current 1231,
• 39:27only 10% did and can see that the.
• 39:36The. CNS relapse rate was
• 39:42higher in the 1231 study.
• 39:46But not overall relapse,
• 39:48and that's what we call Pete sometimes.
• 39:52The Pillsbury Doughboy effect where you
• 39:55shift relapses to bone marrow relapses,
• 39:58but there was no diff.
• 40:00And overall relapses,
• 40:02so this was felt as justification that
• 40:06cranial radiation could be illuminated.
• 40:09So next I'd like to go to an abstract
• 40:12that looks at Linda to mmap versus
• 40:16intensive chemo for first relapse,
• 40:18standard of care in first relapse
• 40:20therapy is to give three blocks
• 40:23of intensive chemotherapy.
• 40:24This is from a European study and
• 40:27they call those blocks HC 1 HC 2
• 40:30and HD three in this study after
• 40:33the first 2 blocks patients were
• 40:36randomized to blend into mmap or two.
• 40:39Third block and then they went to
• 40:42stem cell transplant if they could.
• 40:44And this study also ended early.
• 40:47It was supposed to enroll 202
• 40:49patients and only 100 patients or
• 40:51so were enrolled because there was
• 40:54a clear result that there was an
• 40:57advantage of blended to mmap both in.
• 41:01Add.
• 41:02Event free survival and in time
• 41:07from diagnosis to relapse.
• 41:11There is also an advantage.
• 41:13A significant advantage in overall
• 41:15survival in the blue netuma Bab arm.
• 41:20There was superior MRD remission that
• 41:23was assessed by PCR in the billing
• 41:26to mmap arm overall and it was more
• 41:30remarkable or in those that had a
• 41:33higher tumor burden load initially,
• 41:35so it was most remarkable in those
• 41:40who had more MRD at baseline.
• 41:43There was very notably much
• 41:45decreased toxicity,
• 41:47so while overall toxicity was similar,
• 41:50there was a much lower rate of
• 41:54serious toxicity of 24% versus 43%,
• 41:58and those are greater than Grade 3,
• 42:02so this changes.
• 42:04The construct,
• 42:06because previously the standard,
• 42:08was to get three blocks of chemotherapy.
• 42:14Before transplant in first relapse
• 42:16and this also mirrors a similar
• 42:18see OG study that also found some
• 42:20results that were reported last year.
• 42:27What there is always concerned about
• 42:29neurological toxicity with cytokine
• 42:31release syndrome with netuma.
• 42:33But while there were
• 42:34more neurological events,
• 42:36there were no Grade 3 or higher
• 42:39events in CR S and there weren't.
• 42:42There was really not an increase in severe
• 42:45events or moderate or severe events,
• 42:48so the third study that also relates
• 42:51to blend into my map has to do
• 42:54with whether Blend into my map.
• 42:57Treatment prior to car affects car outcomes.
• 43:02And this is a multi site study.
• 43:05I'm so just there will be
• 43:07a separate car session,
• 43:09but this slide is here if people
• 43:12want to look at this later.
• 43:14But basically a patients T cells
• 43:17are harvested and then they
• 43:20are expanded and then they are.
• 43:23They. Are transfected to T cells
• 43:28via viral vector 2.
• 43:32Have T cell receptor gamma and
• 43:36then often something else.
• 43:38In this case it was for one BB,
• 43:41but it can be different things and
• 43:45it's reinfused and then it can.
• 43:48Go after the particular marker
• 43:51on the on the tumor.
• 43:54So sitting 19 modulation represents a
• 43:57mechanism of resistance to CD 19 targeting.
• 44:00It's both blue 2:00 AM AB and CD19
• 44:03car T cells are associated lineages.
• 44:07Switch CD 19.
• 44:08Lawson CD.
• 44:0919 antigen downregulation becoming dim,
• 44:11and there's just limited impact on
• 44:14the how they impact each other.
• 44:16This was a multicenter study.
• 44:19There were three different car
• 44:21T cell constructs,
• 44:22and it was a seven site study.
• 44:25Their median post infusion followed was
• 44:282.3 years and this occurred over seven years.
• 44:31Um,
• 44:3275 of the 420 patients had had
• 44:36previous blenner,
• 44:37of which 57.3% achieved CR and
• 44:40the median time from last minute
• 44:44to the current Fusion in these
• 44:47patients was 129 days.
• 44:49So there was no difference in those
• 44:52who had had Blender and prior blenna
• 44:55and those who did not in terms of MRD status,
• 45:00whether they had an empty or M3 marrow
• 45:03CNS status, extramedullary disease,
• 45:05or circulating glass.
• 45:06There was a higher rate in those who had
• 45:10prior brunette with the KM T2A R mutation,
• 45:14maybe indicating that there were more younger
• 45:17patients 'cause that occurs more in infants.
• 45:20And and the overall response to the
• 45:24car was great in these 120 patients,
• 45:2891% achieved CR,
• 45:3088% were MRD negative and the
• 45:33relapse rate was 39.8%,
• 45:35however.
• 45:36Blender patients are the ones
• 45:38who had previously know were more
• 45:41likely to have residual disease.
• 45:44Post CD 19 car,
• 45:45so it was 18% if one had prior blina
• 45:49and only 7% if there was previous blender.
• 45:53This also corresponded to worse relapse
• 45:56free survival both at six months.
• 45:58Anna, 12 months and the median relapse.
• 46:01Free survival was twenty months.
• 46:04If one had had previous planner and 45
• 46:07months. If there had been no blender.
• 46:12So we're not is associated.
• 46:14Also was also associated with a higher
• 46:16incidence of CD 19 modulation pre car.
• 46:19So the incidents of CD 19,
• 46:21negative, dim or partial
• 46:23expression prior to the car was.
• 46:25Was higher in prior blender patients,
• 46:2813% versus 6% and in patients in which
• 46:32there was a pre and post Lena CD 19
• 46:36expression 11% had evolution to CD.
• 46:3819 dim expression.
• 46:42Going to change gears now and talk a
• 46:45little bit about toxicities because
• 46:48and listen to young adults were
• 46:51found to have inferior outcomes
• 46:53compared to children and do better
• 46:56when they are treated with PD type.
• 47:00Regiments we can talk about this a little
• 47:04bit more, but there's some trade offs.
• 47:07And so as especially in the early 20s,
• 47:11there is an advantage with pediatric
• 47:14regiments rather than this C vad,
• 47:16this has to be reassessed in
• 47:19the era of cellular therapy.
• 47:23So the goal of this study was to look
• 47:26at bone toxicities and it was found
• 47:28that this is a retrospective study
• 47:31of Dana Farber consortia patients
• 47:34who were up to 50 years and initially
• 47:38they were true with the coli based
• 47:41ones and had 30 weeks of asparagine
• 47:44ace depletion and then later,
• 47:46this changed to PEG.
• 47:48And steroid Dennis Progenies associates
• 47:51Austin across is glucose corduroy,
• 47:54corticoids,
• 47:54disrupt osteoblasts and cause ischaemia.
• 47:56It's not really clear how asparagine
• 47:59ease results in Aston across is,
• 48:02but it is highly associated,
• 48:04maybe due to hypercoagulability in
• 48:07altered lipid metabolism and previous
• 48:09ranges and kids was incidents of
• 48:12osteonecrosis of 69% much higher in
• 48:15adolescence as high in the high teens or 20s.
• 48:19And a good proportion needs surgery and
• 48:22and joint replacement as as 20 year olds.
• 48:26So the goal is to understand
• 48:28this incidence and risk factors.
• 48:30This has this study had 367
• 48:34patients from 25 institutions.
• 48:36And it was found that 17% of them
• 48:40developed osteonecrosis and a
• 48:42median time to event was 1.6 years
• 48:46and 12% developed a fracture with
• 48:49median time to event of 1.4 years.
• 48:53When one looked at risk factors,
• 48:56those under 30 years had a 21% risk,
• 48:59so this is really a condition of
• 49:02adolescents and young adults.
• 49:04With only 8% in those over 30 years
• 49:07and there was a much higher risk
• 49:09in those who had peg based therapy.
• 49:12Rather than E.
• 49:13Coli based therapy,
• 49:15almost a fivefold increased risk.
• 49:18So the potential mechanisms are
• 49:21not known in the later eras,
• 49:24along with Pegasus Virginis
• 49:26more dexamethasone.
• 49:27Dexamethasone is uniformly used and
• 49:29it was proposed that asparagine
• 49:31ease could cause hypoalbuminemia,
• 49:33which decreases dex clearance,
• 49:36and dexamethasone is a steroid more
• 49:39than Prednisone that is a much
• 49:42higher risk of osteonecrosis.
• 49:45And Asperges clearance is higher
• 49:46free collide that Nino Peg Lated
• 49:48is meant to be there along time,
• 49:50and maybe that's it.
• 49:52The investigators plan to look at
• 49:53asparagine ace levels more closely, and this.
• 49:56I'll just summarize this.
• 49:57This abstract would seem to be made for this.
• 50:00In which this group looked at asperges
• 50:04levels and toxicity and found that
• 50:07high levels of this urge nice was
• 50:10not associated with an increased
• 50:12risk of any of the known toxicities,
• 50:15including pancreatitis, thromboembolism,
• 50:17or osteonecrosis.
• 50:19So the the answer it may be not as
• 50:22simple as that and may have to be
• 50:25looked at a little more closely.
• 50:28We have several studies open here
• 50:31at Yale that build
• 50:33on this. We have a study of.
• 50:37Tessa Jean Luc's Loosle Carty 19.
• 50:39Made by Novartis in first line,
• 50:42high risk patients who are MRD positive
• 50:45and end up consolidation that goes up
• 50:48to 25 years of age were investigating
• 50:51blinatumomab in standard risk patients,
• 50:55again with a similar goal of trying
• 50:58to limit chemotherapy eventually
• 51:01and then we're staying ina choose
• 51:03the map in high risk PML patients.
• 51:07To 25 years and we have a study of
• 51:10Pseudomonas derived asparagine ease for
• 51:12those who had hypersensitive reaction to E.
• 51:15Coli drive, despair genese.
• 51:17That's any age.
• 51:18And finally, we have a study where bout
• 51:22to open a blender to mmap with Nivo.
• 51:26And first relapse for patients
• 51:28up to 31 years.
• 51:30So with that,
• 51:31I think you and I hand the floor
• 51:33over to moderate are Doctor Shaw.
• 51:37Thank you very much Doctor Nikolai and talk
• 51:41to Nina for summarizing on the newer data,
• 51:45which were presented at ASH last year.
• 51:50Regarding both pediatric, any Delta LL.
• 51:52So now session is open for questions
• 51:55and when we are waiting for so I think
• 51:59there are some questions there in the chat.
• 52:02Yeah I saw that.
• 52:05Some of them are just comments, but you know.
• 52:09So one of them is addressed to me.
• 52:11Yeah, would you use Hyper C Vad
• 52:14plus blinatumomab approach in your
• 52:16practice today to avoid transplant?
• 52:18So I do have to mention that in that study
• 52:21which I think enrolled about 39 patients,
• 52:2412 patients went to transplant and you know
• 52:2710 of them actually went before relapse.
• 52:30So even folks in MD Anderson
• 52:32who are using this approach,
• 52:34they still using transplant as a modality
• 52:36for this patient after they accomplished
• 52:38CR with without minimal residual disease.
• 52:41So I think the transplant is reserved for
• 52:44high risk patients as defined by their
• 52:46karyotype of maletis pH like status.
• 52:49Anti P53 expression.
• 52:50I have TP 53 mutations so I don't think it.
• 52:53I think it is too soon to say that
• 52:55this particular approach will eliminate
• 52:57the transplant but certainly gives
• 52:59hope to patients who cannot have
• 53:02transplant for whatever reason.
• 53:03An at least maybe a choice for some
• 53:05of those patients who have disease
• 53:08with less risky features.
• 53:10So I and I would say that that is a
• 53:14point of convergence in our literature.
• 53:18So a patient in their 20s,
• 53:21if they came in through a pediatric
• 53:24treatment center, would not accept
• 53:27for certain molecular findings.
• 53:30Would not automatically get transplanted
• 53:32first remission because we have it.
• 53:34We don't use the high perceived backbone,
• 53:37we use the BFM backbone.
• 53:41And use a lot more asparagine
• 53:43ease and methotrexate.
• 53:45But the and and antimetabolites,
• 53:47but the we have we have survival event free
• 53:51survival in the in the 80s in that group,
• 53:54but what I think.
• 53:56But I think the challenges and what
• 53:59we're learning more and This is why I
• 54:02wanted to highlight the toxicity issue.
• 54:05I think what we want to learn
• 54:08more is that it does seem like.
• 54:11Even in patients in their 20s who
• 54:14we call the older patients rather,
• 54:16they have higher rates of infection.
• 54:18They have higher rates of AVN.
• 54:20They have had higher rates
• 54:22of pancreatitis and,
• 54:23and it's not clear how to
• 54:25balance those two things,
• 54:27but they would be treated very
• 54:29differently and they would have
• 54:31good disease free outcomes.
• 54:34So we just want comment.
• 54:36We do use pediatric protocols.
• 54:37Pediatric like protocols become
• 54:39backbone protocols and we're
• 54:40participating in Lion study which
• 54:42uses inotuzumab randomization.
• 54:44So phase three study after initial induction,
• 54:46randomizing patients to two cycles in
• 54:48a tourism up or regular consolidation.
• 54:51This is between H20 and 39,
• 54:53so you know how I perceive what is
• 54:56usually something you would consider
• 54:58for patients who are older than that.
• 55:01And we tried to use again DFM.
• 55:04Backbone augmented BFM backbone
• 55:05protocols for younger patients,
• 55:07so there is a question in the chat.
• 55:10I think both Amarillo Heath and
• 55:12the doctors 8 and that was it was
• 55:14our introduction which reduced us
• 55:16and Doctor Gowda who is one of our
• 55:19adult transplanters asking about.
• 55:22Blender two map consolidation instead
• 55:24of usage of tag asparaginase which
• 55:26is certainly much more difficult
• 55:28for all the patients to tolerate
• 55:30and one of the reasons why you
• 55:32know a lot of people who all the
• 55:34cannot go on pediatric protocols.
• 55:36Can this eliminate usable in a tomb?
• 55:38Up eliminate need for US Virgin eyes?
• 55:41And how do we explain so good outcomes
• 55:43with high perceived cannot be cause
• 55:45younger patients were enrolled well so
• 55:47they tried to enroll patients 14 and older.
• 55:50I think the youngest patients was 17.
• 55:53On that study and the oldest patient was 59,
• 55:56so certainly some of the outcomes can
• 55:59be explained by patient selection,
• 56:01but decent number of these
• 56:03patients have the you know,
• 56:05karyotype abnormalities,
• 56:06Peach like disease and very
• 56:08high number had TP 53 mutations,
• 56:11so it's challenging to say and again
• 56:13you know comparing head to head tag
• 56:16asparaginase containing BFM type
• 56:18protocols with MD Anderson Hyper.
• 56:20See what will not be possible but you know.
• 56:24This is ongoing argument.
• 56:25Which one is better for adult patients?
• 56:29And I think there is one more
• 56:32discussion question to both of
• 56:34you with all this novel Agents
• 56:36of Lena Nine. It is a man.
• 56:38Can you see the use of car T still
• 56:41in the relapse refractory patients?
• 56:43Yeah, you know. So
• 56:45I think there's certainly
• 56:46enroll for car T cells,
• 56:48and we recently had a discussion about
• 56:50young adult who I'm taking care of.
• 56:53And she's actually going for car T cells
• 56:56after she didn't respond to Blender to map.
• 57:00And you know, for some of these patients,
• 57:03it can be a curative treatment.
• 57:05Depending on the construct.
• 57:07So I still hope that some of those patients
• 57:11who fail or who are failed by transplant
• 57:14can be rescued and some well known cases.
• 57:18Nationally where this happened and
• 57:19people survive for many years afterwards.
• 57:21So certainly car T cells is a nice
• 57:23addition to the armamentarium we have
• 57:26for management of these patients.
• 57:28Unfortunately,
• 57:28right now is only for patients
• 57:30or twenty 1625 in.
• 57:33Is only approved for this group
• 57:34of patients and I didn't touch
• 57:36on those studies because I hope
• 57:38some of them will be addressed
• 57:40by the session for two weeks so,
• 57:41but we're hoping that this
• 57:43treatment will become safer and
• 57:44may be used for patients who are
• 57:46all that is definitely something
• 57:47we would like to see for our old
• 57:50LL patients. Yeah,
• 57:51but I'm an maybe at that time we
• 57:54need to just keep in mind that data.
• 57:56Mirali presented with Nina, included in
• 57:59her today is that the prior Lena exposure.
• 58:03May have effect on the Carty outcome,
• 58:06so I think there should be some selection
• 58:08of the patients where we need to right away.
• 58:11Start cleaner if you are really
• 58:13thinking of them offering Cardi,
• 58:15we need to double check whether we need
• 58:17to give those glena front option or not.
• 58:20So I think there should be some selection
• 58:22of the patients who one of the mechanisms
• 58:25of resistance is of course loss
• 58:27of CD 19 expression right so and
• 58:30then you know you lose the target
• 58:32for car T cells so should link.
• 58:34Fortunately it doesn't happen too frequently.
• 58:37So, but nevertheless, the point in world is
• 58:39well taken. Yes no, I agree,
• 58:41and I think one of the things that the
• 58:44investigation that study discussed in this
• 58:46session afterwards with the questions.
• 58:48Is that they would like to understand
• 58:51what was their response to the
• 58:54blender and weather because it
• 58:57may be that even with the karty.
• 59:00I'm sorry even with the CD 19 expression,
• 59:04there's something different about
• 59:06those individuals that needs to
• 59:09be recognized and then the other.
• 59:12Thing is that I think just pairing it
• 59:14with that other study that I presented
• 59:16where the outcomes are better if one
• 59:19receives blina prior to transplant.
• 59:21So one can think about I definitely
• 59:24agree about having car.
• 59:25T in the arm and it arium.
• 59:28But whether one should think about
• 59:30transplant versus party as the next step,
• 59:32and then I think those are those
• 59:34are the complicated equations and
• 59:36we almost have too many choices now.
• 59:39Well, you know,
• 59:40it's nice to have more choices
• 59:42and I wish we have more
• 59:44choices for T cell L.
• 59:45As you know, adults with this disease
• 59:48do not do as well as children.
• 59:50Certainly Laura being.
• 59:51Is that reasonable option,
• 59:53but there are no studies in adults on T cell.
• 59:56Disease of course.
• 59:57Most of the patients have diesel L 85% only.
• 01:00:0015% have T cell disease,
• 01:00:02but this is certainly unmet
• 01:00:04need as not a lot of studies
• 01:00:06addressing this patients right
• 01:00:08now, especially adults, and one of
• 01:00:11the questions which Lloyd is just
• 01:00:13asking with regard to this discussion
• 01:00:15of car T versus other newer regions.
• 01:00:18Can these new region across the CNS?
• 01:00:20Yeah, you know.
• 01:00:23It's challenging questions,
• 01:00:25so you know we know.
• 01:00:28That you know we're not counting
• 01:00:29on Blender to my boy Natuzzi map to
• 01:00:32address CNS disease in these patients
• 01:00:34were excluded from those studies,
• 01:00:36so we don't really have those
• 01:00:38questions answered by the studies
• 01:00:39which led to the approval of these
• 01:00:41drugs in regards to car T cells.
• 01:00:44Again, you know this patients with
• 01:00:45CNS disease are usually excluded,
• 01:00:47so we don't know.
• 01:00:48But we presume that this
• 01:00:50has to be addressed
• 01:00:51separately from systemic therapies
• 01:00:52and there is there are some
• 01:00:54data from CHOP actually for car,
• 01:00:56T for CNS positivity and
• 01:00:58maybe Doctor shopping go into.
• 01:00:59To that a little more,
• 01:01:01but there's it's small numbers,
• 01:01:03but it seems to be covering CNS disease,
• 01:01:06not necessarily testicular disease.
• 01:01:07But yes, that
• 01:01:09is the same as penetration with the Carty,
• 01:01:11and we have seen the success
• 01:01:14rate particularly, and again,
• 01:01:15it's need to be now as parties
• 01:01:17commercially available.
• 01:01:18We need to review those data also down
• 01:01:21the rain so you know, for us, it's a
• 01:01:25move to, you know,
• 01:01:26to zoom out Blender to map,
• 01:01:28you know, without the systemic
• 01:01:30administration of site error.
• 01:01:32Why does it say Terminatrix 8?
• 01:01:33So you know this is certainly
• 01:01:35a very pertinent issue,
• 01:01:36which puts a lot of pressure
• 01:01:38on giving out chemotherapy in
• 01:01:39adequate numbers to those patients.
• 01:01:40As we don't know really,
• 01:01:42you know about the effects of the tool.
• 01:01:47My last question to Doctor Nikolai and
• 01:01:50I'm I'm pediatric transplant are so,
• 01:01:53but looking at this good
• 01:01:55day to our financials,
• 01:01:57demandment cleaner to ma'am.
• 01:01:58Would you consider this in this?
• 01:02:01You're more than 60 year old older adult,
• 01:02:04so how you see in changing your
• 01:02:07practice or your treatment
• 01:02:09algorithm for those group of LL
• 01:02:12patient highly scalable patients
• 01:02:14so you know I think 4.
• 01:02:16Older patients, the question about
• 01:02:19transplant is more difficult because
• 01:02:22you know the outcomes are worse.
• 01:02:25And the administration of this new drugs
• 01:02:27give hope that some of these patients
• 01:02:29may be cured without transplant.
• 01:02:31Having said that, I don't think we know
• 01:02:34yet how many of them will be cured,
• 01:02:36so that's why I cannot clearly
• 01:02:38answer that question.
• 01:02:39And I apologize.
• 01:02:40I have to leave because I'm
• 01:02:42running that your board,
• 01:02:44which starts at 1:00 o'clock.
• 01:02:45When on that note, thank you so much.
• 01:02:48Tower speakers at Doctor Baddour said doctor
• 01:02:50catalytic and overloaded and moderate
• 01:02:52are Doctor Nikita Shad excellent talks.
• 01:02:54And if you have any additional questions.
• 01:02:57Feel free to follow up directly with
• 01:02:59the speakers and we look forward to our
• 01:03:02next session next Friday about benign
• 01:03:04hematology and have a great weekend.
• 01:03:07Everyone take care.
• 01:03:10Bye bye.