Pediatric Leukemia & Acute Lymphocytic Leukemia

February 08, 2021

Information

February 5, 2021

Presentations by Drs. Nina Kadan-Lottick, Nikolai Podoltsev, and Niketa Shah

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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00:38they are still not peer reviewed,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.