Multiple Myeloma

Transcript

• 00:00Actual. Post Ash meeting where a few
• 00:03minutes late but will try to finish
• 00:06on time because I know all of you
• 00:09have other things to go too so it's
• 00:11a pleasure to start this series.
• 00:13I think there has been a lot of new
• 00:15and great development in ash meeting
• 00:18and because of their virtual format,
• 00:20sometimes it's very difficult to
• 00:21catch up with all of those articles.
• 00:24So we are going to have six weekly sessions.
• 00:27The first one today will be about
• 00:29multiple myeloma and we will
• 00:31cover the other important.
• 00:32Disease elements in the next few sessions.
• 00:36So this meeting will be recorded.
• 00:40And we will have the recording
• 00:43available for subsequent viewing.
• 00:45Please remember that this is
• 00:47also see me credited so you can
• 00:50see it get CME credit for this
• 00:52hour and for subsequent meetings.
• 00:55So today our talk will be
• 00:58about multiple myeloma.
• 00:59It's a pleasure to have highly
• 01:02distinguished and expert.
• 01:03Basically speakers today with
• 01:05me from Yale University.
• 01:07So we'll start with the Doctor
• 01:10with Doctor Natalia Nippori.
• 01:11See who's an assistant professor of
• 01:13medicine and she's going to talk to
• 01:16us about updates in the frontline
• 01:18management of multiple myeloma.
• 01:20This will be followed by Doctor Terry Parker,
• 01:23our assistant Professor of Medicine at Yale,
• 01:25who's gonna cover the refractory
• 01:27and relapsed multiple myeloma then.
• 01:29Doctors know far.
• 01:30Power Hour,
• 01:31assistant professor of Medicine
• 01:32who specializes in car T cell
• 01:34therapy and transplantation,
• 01:36especially on the My llama front.
• 01:38She will.
• 01:38Cover those for us and this will go
• 01:41for around 40 minutes after that.
• 01:43At the end we're gonna have 15
• 01:45minutes for questions and answers,
• 01:46so if I can ask you to write
• 01:48down your questions,
• 01:50you can write him throughout the
• 01:51session and send them to us.
• 01:53And just to make sure we can go
• 01:55through all the slides will keep
• 01:57their questions and until the end
• 01:59we're going to have a panelist who
• 02:01is Doctor Sabrina Browning who's
• 02:03our instructor with a focus on
• 02:04amyloidosis and also multiple myeloma.
• 02:06All four speakers will be available at
• 02:08the end to take questions from you.
• 02:10And we look forward to a great
• 02:12presentation so Natalia please stop for us.
• 02:14Thank you.
• 02:19Thank you very much, Doctor Zaidan. Good
• 02:22afternoon and thank you all for joining.
• 02:25As mentioned, these are the panelists
• 02:28joining the discussion today and
• 02:30I will begin by up highlighting
• 02:32initial therapy and biology.
• 02:34Pathophysiology of myeloma.
• 02:36These are my disclosures.
• 02:37I would like to begin by highlighting
• 02:40the work by Doctor Kardashian
• 02:42from NCI who presented the work
• 02:45on the treatment of high risk,
• 02:48smoldering multiple myeloma.
• 02:49With carfilzomib, Lenalidomide,
• 02:51and dexamethasone, this was a phase
• 02:53two clinical in Carrollton study.
• 02:55The primary objective was the study was
• 02:58to determine the minimal residual disease.
• 03:01Negative complete response rates.
• 03:03Another key secondary objectives,
• 03:05including progression free survival,
• 03:07overall survival,
• 03:07duration of MRD.
• 03:09Negative state. This is the overall
• 03:12study design. This study was
• 03:14quite inclusive in that this study
• 03:17included all patients with high risk
• 03:20definition by any of these criteria,
• 03:22including Mayo Clinic,
• 03:24but Seamus Spanish high risk criteria
• 03:27they've defined by flow cytometry based
• 03:30on a barren plasma cell expression
• 03:32as well as Raj Kumar along Grennan
• 03:36Mateus criteria which include plasma
• 03:38cell percentage level of protein.
• 03:40Humana paresis as well as cytogenetic
• 03:43and imaging abnormalities so
• 03:45patients on this study received the
• 03:48induction therapy with carfilzomib,
• 03:50REVLIMID dexamethasone combination.
• 03:51For eight cycles of therapy followed
• 03:54by Lenalidomide maintenance with their
• 03:56usual 20 day cycles for up to two years,
• 03:59followed by observation at
• 04:01every three month interval,
• 04:02with annual staging imaging.
• 04:05Patients in this protocol.
• 04:07Preceded with stem cell harvest.
• 04:09After four cycles of therapy,
• 04:11bone marrow was monitored for MRD
• 04:14assessment with flow cytometry and
• 04:17PET CT scan imaging was incorporated
• 04:20for response assessment at the end
• 04:22of induction and then annually.
• 04:24Overall, 54 patients enrolled and treated.
• 04:27And what's what's interesting is
• 04:29that 37% of patients displayed high
• 04:32risk cytogenetic features and all
• 04:34of the patients met criteria for
• 04:36high risk smoldering based on these
• 04:39definitions and what's remarkable with
• 04:41this study is that sustained MRD,
• 04:43negative complete remission rates were
• 04:46on the order of 70% in this cohort and
• 04:49at two years and five years of survival,
• 04:53sustained MRD negative complete
• 04:54responses remained at 1779 and
• 04:5753% of patients respectively.
• 04:59And overall response rates with
• 05:01this regimen were 100% with 72%
• 05:04achieving complete response and
• 05:0694% of very good partial response.
• 05:08Overall survival and progression
• 05:10free survival are not reached,
• 05:12but at 80 or milestone,
• 05:1491% of patients remain progression free.
• 05:17The treatment emergent adverse events were,
• 05:19as would be expected for this
• 05:22triplet combination.
• 05:23Specifically,
• 05:23side effects of special interest in the
• 05:26form of cardiac toxicity were seen in.
• 05:29Only two 2 patients with heart
• 05:32failure and 4% of this population.
• 05:34So overall this data show that
• 05:36carfilzomib REVLIMID dexamethasone
• 05:38regimen is highly potent.
• 05:40An leads to very deep responses in high risk,
• 05:43smoldering multiple myeloma.
• 05:45Providing further background for this
• 05:47evolving treatment landscape for early
• 05:49intervention and treatment of high risk,
• 05:51smoldering patients who have high risk of
• 05:54progression of greater than 75% / 2 years.
• 05:57Next I would like to highlight
• 06:00the updates on the griefing trial,
• 06:03Griffin trial, early safety,
• 06:05and efficacy data were published
• 06:07in 2020 in Blood Journal,
• 06:10and as you know,
• 06:11this combination of this trial compare
• 06:14daratumumab over RVD compared to the
• 06:17old RVD triplet standard of care.
• 06:20This update focuses on the data
• 06:23on overall responses and MRD,
• 06:25negative responses at the end of
• 06:2712 months of maintenance therapy.
• 06:30So as you know,
• 06:31the trial enrolled patients with
• 06:33newly diagnosed transplant eligible
• 06:34multiple myeloma with good performance
• 06:37status and preserved kidney function.
• 06:39Patients were randomized in one to one
• 06:42fashion to either old standard of care,
• 06:44RVD or they daratumumab CD.
• 06:4638 monoclonal antibody in combination
• 06:48with standard RVD triplet.
• 06:50After four cycles of induction
• 06:51therapy patients went on to
• 06:53receive autologous stem cell transplant.
• 06:56This was followed by two more cycles of
• 06:59consolidation therapy with the same regiment.
• 07:01Followed by REVLIMID maintenance as a
• 07:03single agent as per standard of care.
• 07:06Versus daratumumab REVLIMID combination
• 07:08as maintenance strategy and as
• 07:10you can see with ongoing therapy,
• 07:12responses depend at the end of 12 months
• 07:15of maintenance with Dara, RVD regimen.
• 07:1763% of patients achieved stringent
• 07:19complete responses,
• 07:20and this was significantly better
• 07:21as compared with RVD triplet and in
• 07:24general response rates and depth of
• 07:26responses were greater with Dara,
• 07:28RVD regimen at all treatment time points,
• 07:31and the same is true for the sustained
• 07:34MRD negativity lusting for greater
• 07:36than six months and greater than.
• 07:3812 months with RVD regimen compared
• 07:41to the triplet.
• 07:44The 24 months progression free survival
• 07:47and overall survival data are reported
• 07:50and at this time point and follow up.
• 07:53These are not significantly
• 07:55different statistically,
• 07:55between the two arms, however,
• 07:58predicted PFS appears promising.
• 07:59As you can see, the overall survival
• 08:02curves are overlapping, however,
• 08:04more more time and follow up is required
• 08:07for further read out of the data.
• 08:10With regard to treatment,
• 08:12emerging adverse events,
• 08:13the hematologic toxicity.
• 08:15Of grade three and four
• 08:17degree were higher in Dara,
• 08:19RVD treatment arm as compared
• 08:21to the RVD triplet.
• 08:22Other non hematologic toxicities or also
• 08:25slightly higher compared to the RVD triplet,
• 08:28especially the upper.
• 08:29Story infections were higher with
• 08:31quadruplet versus triplet combination,
• 08:32however, when it comes to grade 3.
• 08:35Four pulmonary side effects
• 08:37such as severe pneumonia,
• 08:38they were not statistically
• 08:40significantly different,
• 08:41so this regimen based on
• 08:43this face to randomize study,
• 08:45offers a very potent
• 08:47frontline induction regimen.
• 08:48Which has been adopted in clinical
• 08:50practice as their reasonable
• 08:52frontline regiment for newly
• 08:53diagnosed patients who are transplant
• 08:55eligible with multiple myeloma.
• 08:57Next I would like to highlight the
• 09:00updates of the Forte trial presented
• 09:03by Doctor Francesca Gay from Italy.
• 09:06As you know,
• 09:0840 trial randomized 474 patients with
• 09:10newly diagnosed multiple myeloma.
• 09:13These were transplant eligible an
• 09:15younger than 65 years of age and they
• 09:19were randomized to one of the three arms,
• 09:23either carfilzomib,
• 09:24cyclophosphamide,
• 09:24dexamethasone or carfilzomib REVLIMID.
• 09:26Dexamethasone followed by transplant.
• 09:28Or carfilzomib REVLIMID dexamethasone
• 09:30for 12 cycles without autologous stem
• 09:32cell transplant and at the randomization.
• 09:35Part 2 patients with randomized to
• 09:37either single agent REVLIMID as per
• 09:40standard of care or combination of
• 09:42carfilzomib produce some inhibitor with
• 09:45REVLIMID as part of maintenance therapy.
• 09:48And at this 45 months of median
• 09:50follow up they sustained MRD negative
• 09:53complete responses for KRD 12 CRV
• 09:57with transplant was 68% and KRD
• 10:00412 cycles without transplant or
• 10:0254% and the same is true for the
• 10:06progression free survival data
• 10:08which favors the KRD plus autologous
• 10:11stem cell transplant at 78% and
• 10:14the next best is KRD 12 cycles.
• 10:18Where is carfilzomib,
• 10:20cyclophosphamide dexamethasone is inferior.
• 10:23And this data present overall very
• 10:25good partial response rates for the
• 10:28time point of randomization Part 2.
• 10:30As you can see the very good partial
• 10:33risk responses on the order of 9694%
• 10:36and what was observed is that MRD
• 10:38conversion rate from MRD positive to
• 10:40negative was significantly higher
• 10:42among patients who received carfilzomib
• 10:45REVLIMID combination for maintenance.
• 10:47The overall survival curves here are
• 10:49really striking for both KRD with
• 10:52transplant as well as KRD 12 regimen
• 10:54and slightly inferior for carfilzomib
• 10:57cytoxan Barbara Cytoxan regimen.
• 10:59So overall,
• 11:00this data show that carfilzomib REVLIMID
• 11:03dexamethasone induction is a very
• 11:05potent regiment for frontline therapy
• 11:07for patients with newly diagnosed
• 11:09multiple myeloma who are transplant eligible.
• 11:12Specifically,
• 11:12KRD improved with transplant,
• 11:14improved progression free survival
• 11:16as compared to the other carbs.
• 11:19And the responses were deeper and depend
• 11:22with continuous KRD maintenance regimen.
• 11:25Next I would like to highlight
• 11:27the report on the
• 11:29elderly non transplant eligible patients
• 11:32with newly diagnosed multiple myeloma.
• 11:35The phase three term Alene trial out of
• 11:39Europe presented by Doctor Thierry Facon
• 11:42who presented the data on this study
• 11:45where 705 patients were randomized to
• 11:48either exacum Abe REVLIMID, dexamethasone,
• 11:51triplet combination versus placebo.
• 11:53REVLIMID. Dexamethasone doublet
• 11:54combination in this transplant ineligible.
• 11:57Elderly population.
• 11:58And the study demonstrated median
• 12:01progression free survival of
• 12:03significantly improved to 35 months
• 12:05compared to 21 months in the triplet
• 12:08versus the tablet RRD combination.
• 12:10And this translated into deeper.
• 12:13Higher rates of deeper responses
• 12:15in the form of higher rate of very
• 12:18good partial response as well
• 12:20as higher rate of complete.
• 12:22An stringent complete remissions
• 12:24SOA based on this data exactly.
• 12:26My problem in Texas Methadone appears
• 12:28to be a reasonable frontline regiment
• 12:30for elderly newly diagnosed subjects
• 12:32who are ineligible for transplant,
• 12:34and it provides a convenient way of
• 12:37all oral combination which may be
• 12:39particularly relevant in the covid era.
• 12:42And finally,
• 12:43I would like to highlight some of
• 12:45the preclinical data which were
• 12:47presented during scientific session,
• 12:49first out of Mayo Clinic Doctor
• 12:52Bakes Eagles experience,
• 12:53who presented the role of dichro gut
• 12:55microbiome in shaping myeloma evolution.
• 12:58In this study,
• 12:59they used VK mix transgenic mice
• 13:01which spontaneously developed
• 13:02democracies and myeloma.
• 13:04The first observation was out of Italy,
• 13:07where they observed that the
• 13:09rate of progression to myeloma
• 13:10was significantly delayed.
• 13:12In the pathogen, free vivarium,
• 13:14and so Mayo Clinic,
• 13:16Arizona joined forces with Jackson
• 13:17Labs and Debrided this Miz and
• 13:20subsequently transplanted them with
• 13:22primary myeloma samples and they
• 13:24treated mice with antibiotics or not.
• 13:26And they observed significant
• 13:28percentage increase in survival
• 13:30of mice treated with antibiotics
• 13:33as compared with the control.
• 13:35Later they identified that Prevotella,
• 13:37one of the microorganisms in the gut
• 13:41microbiome significantly impacted
• 13:42the burden of multiple myeloma.
• 13:45So this data hypothesize that the
• 13:47certain micro bacteria in the gut
• 13:50microbiome such as prevotella Trib,
• 13:53actor bacteria, Bacteroides,
• 13:54and Clostridia, can provide uncontrolled.
• 13:56Stimulation of the TH.
• 13:5817 responses and regulatory T cell
• 14:01responses and this signal from got
• 14:03may translate into increased child 17.
• 14:06Another immune changes which further
• 14:08promote growth of myeloma cells and
• 14:10progression of disease and this
• 14:12concept provides important Ave for
• 14:14the therapeutic interventions for
• 14:16prevention of disease and finally
• 14:18elegant work presented by Doctor Irene
• 14:20Ghobrial of Dana Farber who performed
• 14:23single cell RNA sequencing on the
• 14:25spectrum of specimens from healthy
• 14:27volunteers to M Gus to smoldering myeloma.
• 14:30Two full blown clinical multiple myeloma
• 14:33and highlighted the composition and
• 14:36evolution of immune microenvironment
• 14:37changes during which with time and
• 14:40progression of disease there is
• 14:42significant increase in the numbers
• 14:44of regulatory T cells as well as
• 14:47increased percentage of NK cells
• 14:50that predominantly express CX,
• 14:52CR4 and CX3 CR,
• 14:53as well as increased subsets of CD16
• 14:55monocytes and this data provides
• 14:58significant background through
• 14:59which one could design immune
• 15:02therapeutic interventions to possibly
• 15:04eradicate irregular.
• 15:05Regulatory T cells and other
• 15:07immune interventions in order to
• 15:09prevent the disease progression.
• 15:10So with that I will stop and would
• 15:13ask Doctor Terry Parker to highlight
• 15:15the updates on relapse refractory
• 15:17multiple myeloma Andale amyloidosis.
• 15:19Thank you. Thank
• 15:23you to Talia.
• 15:52Unless you get the top.
• 15:59I will be reviewing updates
• 16:04from ASH and relapse refractory
• 16:10multiple myeloma anael Android.
• 16:15I have no disclosures.
• 16:16There are multiple abstracts this year
• 16:19in relapsed refractory multiple myeloma.
• 16:21They range from new combinations
• 16:23of FDA approved agents to immuno
• 16:25therapies with antibody drug,
• 16:27conjugate San, bispecific,
• 16:28T cell engager's.
• 16:30I will start by reviewing two
• 16:32abstracts utilizing currently
• 16:33FDA approved agents in selinexor.
• 16:35An easy Texas map.
• 16:37Stamp was a phase one B2 clinical
• 16:39trial that evaluated varying doses
• 16:42and dose schedules of selinexor,
• 16:45pomalidomide and dexamethasone.
• 16:46Primary objective of the trial which
• 16:49identify the recommended phase two dose
• 16:52and evaluate the overall response rate.
• 16:5465 patients were accrued 20
• 16:56at the recommended phase.
• 16:58Two dose.
• 16:59The meeting number of prior therapies
• 17:02was three and 75% of patients
• 17:04were refractory to Lenalidomide.
• 17:06The table here illustrates the very.
• 17:08Doses of weekly selinexor with the
• 17:11recommended phase two highlighted in red,
• 17:13which ends up being 60 milligrams of
• 17:16selinexor weekly comma, 4 milligrams.
• 17:1821 out of 28 days and X 40 milligrams weekly.
• 17:23The overall response rate was 54.3% in
• 17:25palm naive patients with progression
• 17:27free survival of 12.3 months.
• 17:30There overall response rate decreased
• 17:32to 35.7% and those that were
• 17:34Palmer factory in patients dosed
• 17:36at the recommended phase two dose.
• 17:39The overall response rate was 60%
• 17:41treatment related adverse events
• 17:42were similar to what has been
• 17:44seen with selinexor in Palm.
• 17:46These included nausea,
• 17:47mild depression and fatigue.
• 17:48I chose to highlight this trial as
• 17:51it presents an all oral regimen
• 17:53which is appealing to our patients,
• 17:55especially in the relapse refractory setting.
• 17:57I also wanted to point out the different
• 18:00selinexor dosing compared to the storm trial,
• 18:02which was 80 twice a week and
• 18:04the Boston clinical trial,
• 18:06which was 100 milligrams weekly.
• 18:08There was an improved overall response rate.
• 18:10Free survival compared to historical
• 18:13data with palm index which is
• 18:1531% informance respectively.
• 18:16In patients refractory to
• 18:19Lenalidomide and worked as a matter.
• 18:21Doctor Martin presented at the interim
• 18:23analysis from the Akuma trial patients
• 18:26were eligible for this trial if they
• 18:28had one to three prior lines of therapy.
• 18:30No prior history of carpal zenmap,
• 18:32and we're not refractory to anti CD 38.
• 18:36302 patients were randomized to
• 18:37receive isatuximab carfilzomib dex
• 18:39versus carfilzomib dex with the
• 18:41primary endpoint of progression free
• 18:43survival and secondary endpoints
• 18:44of overall response.
• 18:46VGP RCR emoji negativity rates from
• 18:48those not familiar East Texas map is
• 18:51an IgG one monoclonal antibody against CD.
• 18:5338 minimal residual disease was assessed
• 18:55for this trial in the bone marrow aspirates.
• 18:59If patients who achieved at least Avicii
• 19:01PR by next generation sequencing at
• 19:0310 to the minus mix sensitivity level.
• 19:06Yeah, central lab.
• 19:08The best overall response was 86.6%,
• 19:11with 72.6% of patients achieving
• 19:13AVGPR and 39.7 as CR.
• 19:16In these attacks,
• 19:17map ARM MRD negativity rates
• 19:19were 41.4% compared to 22.9%.
• 19:22The CR rate of 39.7% was felt to
• 19:25be under estimated given Eastern
• 19:27text mode interference.
• 19:29Therefore, for 27 patients with an ear,
• 19:32see are defined as a positive
• 19:36immunofixation for IgG cap on I.
• 19:39Or potential CR were evaluated.
• 19:40The Anaspec 15 of the 27 were
• 19:43found to be M protein negative.
• 19:45Increasing the CR rate to 45.8%.
• 19:49So talking points from this
• 19:50trial without the combination of
• 19:52East Texas map carfilzomib index
• 19:54resulted in improvement in overall
• 19:56response rate CR V GPR in Aberdeen.
• 19:59Negativity rates had an
• 20:00impressive CR rate of 45 point 8%.
• 20:03Again in patients with one to three
• 20:05prior lines of therapy and MRD,
• 20:08negative negative CR rate of 24%.
• 20:10MRD negativity in both arms was
• 20:12associated with a longer progression,
• 20:14free survival and the potential
• 20:16to achieve MRD negativity,
• 20:17which should be independent of
• 20:19adverse prognostic characteristics.
• 20:20Catches ISS stage three disease.
• 20:22We don't involvement or a gain of 1 Q 21.
• 20:26And moving on to the Immunotherapy's
• 20:29Doctor Kumar presented first in
• 20:31human phase one trial of MEDI 2228,
• 20:33which is an antibody drug conjugate
• 20:36that targets the extracellular
• 20:38domain of human be CMA.
• 20:39The primary endpoints were
• 20:41safety and tolerability.
• 20:42The trial enrolled 82 patients
• 20:4441 in the expansion.
• 20:46Copart two patients had great for
• 20:48thrombocytopenia at the 0.2 mix perchik dose.
• 20:51Therefore, the maximum tolerated dose
• 20:53was 0.1 for mixer cake given Q three weeks.
• 20:56Treatment related adverse events
• 20:58included photophobia.
• 20:59Thrombocytopenia rash dry on pleural
• 21:01effusion at the maximum tolerated dose,
• 21:03the overall response rate was 66% with
• 21:06the duration of response at 5.9 months.
• 21:09Unlike the currently FDA approved
• 21:11ADC of Blanton map,
• 21:12no Keratopathy was observed.
• 21:14However,
• 21:14photophobia credit 60% of patients at
• 21:17the 0.1 four make for kiddos with a
• 21:20median time to onset of two months,
• 21:23which is roughly 2 cycles.
• 21:25This did improve in 37% of
• 21:27patients and resolved in for.
• 21:29Is holding up the medication
• 21:31this agent is moving forward,
• 21:33looking at varying adjusting schedules.
• 21:36They must pass it.
• 21:37Ash this year was for the
• 21:39bispecific T cell engager's.
• 21:41This chart is adapted from 1% in by
• 21:44Doctor Chary during his educational
• 21:46session on you know, therapies.
• 21:47Here.
• 21:48I have listed all the bytes
• 21:50that RBC may targeted that were
• 21:52presented at this year's ASH.
• 21:54Therefore,
• 21:54oral abstracts and one poster
• 21:56do just time constraints.
• 21:57I will be just talking about to Clifton AB,
• 22:01which had the largest patient accrual.
• 22:04So as mentioned to custom AB is
• 22:06ABC May CD three byte 84 patients
• 22:09received an Ivy dose with 44
• 22:11receiving subcutaneous dosing.
• 22:13The median number of prior treatments
• 22:16for these patients were six and
• 22:1881% were triple class refractory.
• 22:20By that I mean they were refractory
• 22:22to an image of proteasome inhibitor,
• 22:25an anti CD 38 monoclonal antibody.
• 22:27Step up Justin was utilized prior
• 22:29to the first full dose to decrease
• 22:32the risk aside entirely syndrome.
• 22:34Notice TRS in subsequent slides,
• 22:36adverse events and no see Russ did
• 22:39occur in 55% of patients with the
• 22:41Ivy dose and in 50% receiving the
• 22:44subcutaneous dose with the median time
• 22:46to onset of one to two days respectively.
• 22:49However, no Grade 3 events were noted.
• 22:52Neurotoxicity hurting 5%
• 22:53with two Grade 3 events.
• 22:55Injection site reactions in 32 and there
• 22:57was one death attributed to pneumonia.
• 23:00The recommended phase two dose based on
• 23:02setting safety advocacy and pharmacokinetics.
• 23:04Is 1500 micrograms per kilogram at this test,
• 23:07the overall response rate was 73%,
• 23:10as outlined here,
• 23:11with the median time to responsive one month.
• 23:15So again, take home points.
• 23:16The recommended phase two dose moving
• 23:19forward will be 1500 micrograms
• 23:20per kilogram weekly, subcu.
• 23:22This was a heavily pretreated
• 23:24patient population,
• 23:25as 39% work at refractory,
• 23:27and in this patient population that
• 23:29overall response rate was 73%,
• 23:31which is very encouraging with 23% CR
• 23:33and 55% VG PR at the recommended phase,
• 23:36two dose eat at the 11 evaluable patients
• 23:39were energy negative and there's a
• 23:42potential for durable responses as
• 23:4415 out of 16 patients were alive.
• 23:46No progression at the median
• 23:48follow up at 3.9 months.
• 23:50The other two by specifics that
• 23:52I would like to highlight include
• 23:55a bispecific targeting STR.
• 23:57H5 which stands for St receptor
• 23:59homolog 5 which is a type one membrane
• 24:02protein expressed on plasma cells with
• 24:05near 100% prevalence for myeloma.
• 24:07So Savasta map is this bispecific
• 24:10antibody that targets approximately
• 24:11the domain of FCR H5 in C3.
• 24:14Given Ivy Q,
• 24:15three weeks again with one step up,
• 24:18dose 53 patients were accrued
• 24:20with 51 being a valuable.
• 24:22And 21% of now had prior PC may
• 24:25directed their adjusting schematic
• 24:26is illustrated here and the maximum
• 24:29tolerated dose was not reached.
• 24:31Therefore,
• 24:31dose escalation is on going in
• 24:34this trial safety to note 76%
• 24:36of patients did have CR,
• 24:38S 28% had another event which
• 24:40occurred in the setting of CR S
• 24:43and 23% infusion related reaction
• 24:45in individuals who received at
• 24:473.6 milligrams step up.
• 24:48This at least a 20 milligram full dose.
• 24:51The overall response rate was.
• 24:5353% there was a 63% overall response
• 24:56rate in patients who had received
• 24:59prior PCMI directed therapies.
• 25:02So this represents a new
• 25:03target for multiple myeloma,
• 25:05with the maximum tolerated
• 25:06dose not being reached.
• 25:08Importantly,
• 25:08Seeress did occur and 76% of patients,
• 25:11but there was only one grade three event,
• 25:14which was an elevated transaminase
• 25:16that resolved encouragingly responses
• 25:18were observed in patients who
• 25:19had prior be CMA as we will need
• 25:21therapies for patients who progress
• 25:23after car T and Adcs responses
• 25:25were seen irrespective of target
• 25:28expression levels in patients
• 25:29that have been assessed to date.
• 25:31The last by specific is till cotton
• 25:34AB which binds GPRC 5D which stands
• 25:37for G protein coupled receptor family.
• 25:39See Group 5 member in D which is an
• 25:42orphan receptor whose transcript is
• 25:44expressed in primary myeloma cells.
• 25:46This again was a phase one dose
• 25:49escalation study to identify
• 25:50the recommended phase.
• 25:52Two dose then rolled 157 patients.
• 25:54102 received an Ivy dose
• 25:56and 55% cutaneous dose.
• 25:57The dose in schematic is outlined
• 26:00here with the highlighted in green.
• 26:02Being the recommended phase,
• 26:04two dose of 405 micrograms per
• 26:06kilogram and looking at key safety
• 26:08side of Henry Lee syndrome as seen
• 26:10in 68% of patients but no grade
• 26:13three at the recommended phase,
• 26:14two dose T styles duration 38 an
• 26:17injection site reaction in 21.
• 26:19The overall response rate was
• 26:2069% of the recommended phase.
• 26:22Two dose, and 200 Tupac
• 26:24refractory patients did respond.
• 26:25The medium kind response was
• 26:27one month similar to what's been
• 26:30shown with other BI specifics.
• 26:32Take her messages for this trial.
• 26:34Is that again,
• 26:35this represents another two new target
• 26:37in my lumbar for advice specific,
• 26:39it is a subcutaneous dose which
• 26:41may allow for Q two week dose sing,
• 26:43which would be more patient,
• 26:45convenient as the other bytes I've
• 26:47discussed are all weekly dosing.
• 26:49Again, responses were observed
• 26:50in heavily pretreated patients,
• 26:51including those where pepper
• 26:53factory and there's a possibility
• 26:54of durable responses as there was
• 26:56no progression at the medium,
• 26:58follow up at 3.7 months and they know.
• 27:02Have a duration of response
• 27:04that's over two years.
• 27:06The time remaining I'll just quickly
• 27:08touch upon three trials for a lamb alloy,
• 27:11two in the frontline setting
• 27:12and one in relapsed refractory.
• 27:14The Andromeda's trial was a phase
• 27:16three randomized trial for newly
• 27:19diagnosed Ale Android patients.
• 27:20Trainer idiot patients were
• 27:22randomized to receive cyber deed.
• 27:24Cytoxan process of dexamethasone
• 27:26plus or minus daratumumab which
• 27:28is a CD 38 monoclonal antibody.
• 27:31The primary endpoint of this trial was met,
• 27:34which was haematological CR at
• 27:3656.9 versus 18%.
• 27:38I want to evaluate the impact of
• 27:40achieving a deep reduction in serum
• 27:42free light chains on a composite
• 27:44endpoint of major organ deterioration
• 27:46progression free survival in order
• 27:48to evaluate at the production the
• 27:50evaluated a involved free light
• 27:52chain of less than 20 milligrams
• 27:54per liter and the difference between
• 27:56the involved versus uninvolved free
• 27:58light chain of less than 10 and what
• 28:01they showed it is patients with in
• 28:03the daratumumab arm achieved all of these.
• 28:0671.3% of patients had an involved.
• 28:08Reaching less than 20 and 65.6% had
• 28:11the difference being less than 10.
• 28:13This resulted in improved major organ
• 28:15deterioration progression free survival,
• 28:17which is illustrated in the graph here.
• 28:20So conclusion for this trial.
• 28:22The addition of daratumumab decide
• 28:24where D resulted in improvement in
• 28:27haematological response utilizing
• 28:28a variety of measurements.
• 28:30This resulted in improved rates of
• 28:32cardiac in renal organ response.
• 28:34In addition,
• 28:35haematological progression was
• 28:36improved 23 versus 47% and rates
• 28:39of cardiac arrhythmia failure will
• 28:41also improve with the addition
• 28:43of daratumumab at 3% versus 13%.
• 28:45This represents potential and you
• 28:47standard of care for these patients
• 28:50without friends. Treatment for Alienware.
• 28:52The second trial apps for Android is Cal 101,
• 28:56which is a nail Android 5 World reactive IgG.
• 28:59One monoclonal antibody.
• 29:00This was first mentioned at ASH in 2017.
• 29:02This is a phase two study.
• 29:04Determine the recommended phase
• 29:06three dose when given in combination
• 29:08with cyber DM Part A or with cyber D
• 29:10plus daratumumab in Part B patients
• 29:12were started at a dose
• 29:13of 500 mics per meter squared and
• 29:15this was escalated to the maximum
• 29:17tolerated dose with 1000 mics per
• 29:19meter squared weekly for four weeks
• 29:21and then every other week there
• 29:23were no infusion related reactions.
• 29:24Treatment related adverse events were all
• 29:27less than grade two and included rash,
• 29:29nausea, vomiting, and diarrhea.
• 29:31I've seen here also in patients
• 29:33with renal involvement had an organ
• 29:35response defined as a percent
• 29:37decrease from baseline in 24 hour
• 29:39approaching area of greater than 30%,
• 29:41and there was one cardiac response.
• 29:43I probably MP.
• 29:44So this compound is moving forward
• 29:46at the recommended Phase 3 to 7000
• 29:49mixed per meter squared weekly,
• 29:51and then times for than every other week.
• 29:54There are currently two phase
• 29:55three trials open,
• 29:56one for male stage 38 patients and
• 29:59the other for stage 3B patients,
• 30:01so I'm sure we will be hearing
• 30:03more about this compound to come.
• 30:05The last trial in relapsed refractory
• 30:07Elana Lloyd was with ice attacks
• 30:09map and this results from the
• 30:11Southwest Oncology Group 1702 trial.
• 30:13All patients who have received
• 30:14at least one prior line of.
• 30:16Therapy.
• 30:17And hadn't had one organ system involvement.
• 30:21Received text messages to 20
• 30:22minutes per meter squared.
• 30:24The primary endpoint was
• 30:25haematological overall response rate,
• 30:27which was 77% with a one year estimated.
• 30:30Overall survival of 97% when
• 30:32your estimated progression.
• 30:33Free survival of 85%.
• 30:34The safety and response data was
• 30:36similar to that previously reported
• 30:38with Darren to in our monotherapy
• 30:40in relapsed refractory Elana LA
• 30:42Justice and provides another
• 30:44treatment option for these patients.
• 30:46With that I will finish and pass it along
• 30:49to doctor Know Far Bar to finish up.
• 31:03and when the focus for the most
• 31:06part on car T cell therapies for
• 31:10relapsed refractory myeloma patients
• 31:12and then close with a few comments
• 31:17on autologous stem cell transplant
• 31:19for the newly diagnosed patients.
• 31:23So I want to remind everyone that
• 31:25patients who are we have been
• 31:28refractory to image producer members.
• 31:30An anti CD 30 antibodies have extremely
• 31:33poor prognosis with immigration,
• 31:35median progression,
• 31:35free survival of two to six months
• 31:38and most of them not living past
• 31:41one year and some terminology to
• 31:43remind you as those are refractory
• 31:46to the three classes of drugs or
• 31:49called triple or factory and those
• 31:51are refractory to two images.
• 31:53Two peas and anti clone the anti CD 38
• 31:57antibodies are called penta refractory.
• 31:59I'll be using those terminologies
• 32:02in my next slide.
• 32:04So the first study I'm going to
• 32:07be highlighting here is using
• 32:09the car T cell called Ida cell.
• 32:12In short,
• 32:13formerly known as BB 2121 an
• 32:15If you see here the construct,
• 32:18it has a binding domain against
• 32:20the CMA on the tumor cell and the
• 32:23intracellular domain includes the
• 32:25costimulatory molecule form 1B B.
• 32:27This was a phase one study and study design.
• 32:31Patients underwent local pheresis
• 32:32and then the cell product was
• 32:35taken to manufacturing.
• 32:36And then delivered back to the patient's car.
• 32:39T cell infusion before the patient
• 32:42gets the infusion, they get lifted,
• 32:44depleting therapy with food,
• 32:46European and cytoxan.
• 32:47And this is pretty routine
• 32:49schema for most Corti studies.
• 32:52In this study there were 62 patients.
• 32:55Majority of the patients received the
• 32:571:50 and the 450 million cells per cagey.
• 33:01This was a heavily pretreated population
• 33:03with median line of prior therapy of 670%.
• 33:07Being triple refactoring 27% had high
• 33:10risk cytogenetics and 37% or high
• 33:14risk by having extramedullary disease.
• 33:18So looking at the safety and efficacy,
• 33:20all patients have cytopenias and this
• 33:22is from the link for depleting therapy
• 33:25which is routinely used for Carty.
• 33:27I'm more focusing going to be
• 33:29focusing on this CRS decided kind
• 33:32release in German that I cans,
• 33:34which is the neurotoxicity we
• 33:35see with car T cell therapies,
• 33:38so 75% of the patients had CRS with
• 33:41about 6% having Grade 3 and above.
• 33:43In terms of the neurotoxicity,
• 33:45which can manifest as an several Catholic
• 33:48picture, but can be as severe as.
• 33:50Brain edema seizures 34%.
• 33:53I can't with very rare incidents of
• 33:59having Grade 3 or above less than 2%.
• 34:03Infections are very common in
• 34:05this patient population.
• 34:07Is we all know and 75% had infections
• 34:10with 23% being Grade 3 or above.
• 34:14Now look at the efficacy,
• 34:16it's quite impressive with an
• 34:18overall response rate of 76%.
• 34:21In this relapse population with the
• 34:23CR rate of 33% at the median Phillip.
• 34:27And that the response rate was
• 34:29dose dependent.
• 34:30So with higher doses they saw a
• 34:33higher overall response rate and
• 34:35the median follow up of 18 months.
• 34:37The great meeting duration of
• 34:40response was about 10 months and
• 34:42this was not affected by age,
• 34:44extramedullary disease stage
• 34:45and 50% of responders retained
• 34:47the response at over two years.
• 34:50This graph here shows you that the
• 34:54deeper responses actually lead to
• 34:56longer duration of response with those
• 34:58with CR exemplified by the blue line.
• 35:01Here having a median duration of
• 35:04response of almost 15 months.
• 35:06The median progression free survival was
• 35:0988 months with a very impressive meeting
• 35:13overall survival of 30 four months.
• 35:16Perhaps these patients were able
• 35:19to then get further treatments to
• 35:21lead to this impressive overall
• 35:23survival in this patient population.
• 35:25The next Accardi study is the
• 35:27car to Tud one study,
• 35:29and this uses a different car T product
• 35:32called still to sell it 2 bonds to be CMA,
• 35:34but it has two binding domains.
• 35:36As you can see here,
• 35:38and it also uses a four 1B B like
• 35:41the Ida cell.
• 35:42This study there was close to
• 35:45100 patients enrolled with a
• 35:48median follow up of 12.4 months,
• 35:51also heavily pretreated population
• 35:53with the meeting lines of prior
• 35:56therapy of 687% were triple refractory
• 35:58with 42% being penta refractory.
• 36:0123% high recited genetics and
• 36:0313% and extramedullary disease.
• 36:07Now let's look at the toxicity of cell
• 36:09to cell. So very high rates of CRS.
• 36:11Nearly all patients got this,
• 36:13but for the most part they were
• 36:15grade one and grade two with
• 36:16only 5% having Grade 3 or above.
• 36:18As you can see,
• 36:19there is 70% use of totsuzen Maps,
• 36:21but they were even using the dose
• 36:24who's map for some of the great
• 36:26ones which we do sometimes do.
• 36:27I can't see Neurotoxicity was seen at
• 36:3016% with two percent Grade 3 or above,
• 36:33which is similar to the prior study as well.
• 36:36They do comment on this other nurse
• 36:39Texas City that is more delayed and also
• 36:42sometimes not reversible like that.
• 36:44I can occur in about 12% of the
• 36:47patients in this involved movement
• 36:49or neurocognitive changes.
• 36:50There are investigating this further
• 36:52in in their subsequent studies as well.
• 36:54There is 20% of Grade 3 and
• 36:57above infections an.
• 36:58Of their 14 deaths,
• 36:596 or related to sell to sell
• 37:01what stands out in this study.
• 37:03It also is that there was a later onset
• 37:06of CR S with a median of seven days
• 37:08compared to two and other studies.
• 37:10They hypothesize this is because of
• 37:13the timing of the T cell expansion.
• 37:15Now the efficacy is very impressive,
• 37:18with an overall response rate
• 37:20almost 196.9% with the stringent
• 37:22CR of 67% on high rates of MRD,
• 37:25negativity responses are ongoing
• 37:27in 72% of patients.
• 37:29They have not reached their
• 37:31median progression free survival,
• 37:33and they estimated the 12 month
• 37:35progression free survival at 76%.
• 37:38As you can see here by the next graph
• 37:41that the progression free survival
• 37:43was improved for those patients who
• 37:46were in deeper response like that.
• 37:49Sponse as opposed to the very
• 37:52good partial response.
• 37:54So.
• 37:55I've showed you two Carty studies
• 37:57that have very impressive results.
• 38:00However,
• 38:00there is still room for
• 38:02improvement on car T
• 38:03cell products.
• 38:04Of course, not everyone responds.
• 38:06Not everyone responses deeply,
• 38:08and we still have significant
• 38:10toxicity that we need to mitigate.
• 38:12So not all T cells are created equal as
• 38:15you move toward the more early T cell,
• 38:19the T cells in earlier development,
• 38:21for example, like the steps on memory T cell,
• 38:24these memory like.
• 38:26Cells have certain qualities
• 38:27that make them attractive.
• 38:29There long lived.
• 38:30They have ability to self renewal
• 38:33and in others Carty studies these
• 38:35memory like T cells correlated with
• 38:38peak expansion and sustain response.
• 38:40Additionally,
• 38:41there's potential for less
• 38:43toxicity because there's gradual
• 38:45differentiation into the effectors,
• 38:46thus more gradual tumor killing
• 38:49and perhaps less static on release.
• 38:52So this concept was used in
• 38:55the next study that PBC MA 101
• 38:58prime Phase 1 two study.
• 38:59They use this technology called piggyback,
• 39:02which preferentially makes
• 39:03stem cell memory T cells.
• 39:05It's made with transposons,
• 39:06which are plasmids instead of lentivirus,
• 39:08which is what the prior
• 39:10Carty product we're using,
• 39:12and this one has a large carrying
• 39:15capacity so we can deliver
• 39:17a lot of genetic material.
• 39:20This too was directed against BCM of course.
• 39:23So this is the study design.
• 39:25I don't want to go into detail,
• 39:27but I want to highlight a few things.
• 39:30Not only were they looking at
• 39:32different doses who dose escalation,
• 39:33but they had the various cohorts
• 39:35as you can see here.
• 39:37Now I want to point out that there are
• 39:39using Lenalidomide in different time points,
• 39:41not only for anti tumor activity but also
• 39:44for improvement of T cell functionality.
• 39:46So what I do on the focus on is the
• 39:48response in Texas City on the 1st graph.
• 39:51Do you see different overall response rate?
• 39:54In different doses and they range from
• 39:57anywhere 40s to 70% overall response rates.
• 39:59They did not feel like there was a
• 40:03dose dependent relationship here.
• 40:04Thought that we're seeing a good
• 40:07responses even with low doses
• 40:09and marked late you see that they
• 40:12were really low rates of CRS.
• 40:14It's 17%.
• 40:15So this exemplifies how a manufacturing
• 40:18technique can manipulate the T cell
• 40:21product to optimize the toxicity
• 40:23and efficacy and potentially bring
• 40:26this cellular therapy to the
• 40:28outpatient setting at some point.
• 40:32There are potential issues with car T cells,
• 40:35right?
• 40:35So it takes time to manufacture the cells.
• 40:38Some patients don't have that time.
• 40:40You know we see this patient
• 40:42needs treatment right away.
• 40:44We can't schedule the Pheresis
• 40:46in manufacturing and so forth.
• 40:47Additionally,
• 40:48the quality of autologous T cells
• 40:50might be decreased in this relapse,
• 40:52refractory patient population and
• 40:54re treatment can be difficult,
• 40:56sometimes hard to collect enough
• 40:58cells and be able to expand them.
• 41:01So this brings us to the off the
• 41:04shelf Alo 7:15 Carty targeting
• 41:06the CMA in this Phase one study.
• 41:10This is the construct here.
• 41:13What the the two key attributes is
• 41:15a knockout of CD 52 which allows
• 41:17for selective room for depletion.
• 41:19All lymphocytes have CD 52 by
• 41:21the way and it
• 41:23also has a knock out of the
• 41:25TCR gene to eliminate GV HD.
• 41:28It used a slightly different
• 41:29regiment for Lymphodepletion,
• 41:31so it's flu side plus the anti
• 41:33CD 52 versus Cyan anti CD 52 but
• 41:36the one I'm highlighting here.
• 41:38The flu sign anti CD 52 is the one
• 41:41they're presenting now but there is
• 41:43potential for maybe a less toxic went
• 41:46for the cleaning therapy here so also
• 41:49heavily pretreated population and
• 41:51almost all the more pent pent Xposed
• 41:54about half of them had high recited
• 41:56genetics and 23% and extramedullary disease.
• 41:58There were 31 patients available for safety.
• 42:01And they had 47% serious with no grade.
• 42:04Three. No, I can't.
• 42:06And no GV HD.
• 42:08So a very promising toxicity profile.
• 42:10Again, this is a very good drug that I
• 42:13think we're going to see more studies
• 42:16with an more follow up will tell
• 42:19us more information, of course. Um?
• 42:22The efficacy of alacarte in 10 patients,
• 42:26so they had various doses.
• 42:29There are temptations in the dose Level
• 42:323 and it follow up of 3.2 months.
• 42:36The overall response rate was 60%
• 42:38with a very good partial response
• 42:42or higher or 40%.
• 42:44Now on the shift gears,
• 42:46a little bit to the good old autologous
• 42:50stem cell transplant for myeloma.
• 42:53This is an update of the FM 2009 study
• 42:56that was originally presented in 2017,
• 43:00so now it's a follow up of almost 90
• 43:03months just to remind people to phase
• 43:06three study newly diagnosed patients.
• 43:09Arm A is looking at testing RVD
• 43:12induction followed by maintenance
• 43:14Lenalidomide for one year,
• 43:16and RB is RVD induction followed
• 43:19by transplant,
• 43:20followed by RBD consolidation
• 43:22and then maintenance.
• 43:23In the limit for a year so their updated
• 43:27median progression free survival was
• 43:3047.3 months in arbutus to transmit arm
• 43:34versus 35 months in the non transplant arm.
• 43:38They had very nice overall response.
• 43:41I'm sorry very nice eight year.
• 43:44Median overall survival
• 43:45about 6060% in both groups,
• 43:46so they were not difference.
• 43:48There is no difference there and I
• 43:50just want to highlight that about 1/3
• 43:53of the patients in the transplant
• 43:55arm did not relapse after 8 years of
• 43:58follow up and these are patients that
• 44:00are not being treated continuously.
• 44:02They're only getting one year of maintenance.
• 44:05This is not the practice we do here
• 44:07in America and I think there's going
• 44:09to be more information with the US
• 44:12portion of this study looking at continuous.
• 44:15REVLIMID and whether that is
• 44:17going to affect this progression.
• 44:20Free survival benefit.
• 44:21Now,
• 44:21in terms of MRD transplant did improve
• 44:25the energy negativity rate from 20 to
• 44:27about 30% and in this graph you see
• 44:31the progression free survival based
• 44:33on MRD negative state and the transplant.
• 44:36So in red you see those
• 44:38patients who are MRD negative.
• 44:40While I'm blue there emordi positive.
• 44:44And you can see that the transplant,
• 44:47exemplified by the solid line
• 44:50improved progression free survival
• 44:52even in the MRD negative patients.
• 44:55Next study I'm going to highlight
• 44:57was already presented by
• 44:58Natalia, but I want to focus on one aspect.
• 45:01Here is the Forte study.
• 45:03Not going to go into the design.
• 45:05This was already discussed,
• 45:06but one take home messages this
• 45:09so while you see in the first
• 45:11graph here the response rate,
• 45:12the response rates,
• 45:13and an MRD negative status was similar
• 45:16in KRD versus kerdi plus transplant.
• 45:18The one year sustain energy
• 45:19negativity was higher for the kerdi,
• 45:21plus transplants as you can
• 45:23see here in the second graph.
• 45:26And this translated into improved
• 45:28progression free survival for all subgroups,
• 45:30including the high risk patients.
• 45:32So I think to conclude on on this
• 45:35section is that transplant is
• 45:37still a great treatment for upfront
• 45:40patients who can tolerate it.
• 45:42And with this I will close my
• 45:45talking will move towards our Q&A.
• 45:50Great thank you know far and
• 45:53thanks everybody for beautiful presentations.
• 45:55I do not see any active questions.
• 45:58Doctor up they had an earlier question
• 46:01which I answered the smoldering
• 46:03trial date that I presented.
• 46:05Patients who are newly diagnosed as
• 46:08opposed to those in long term follow up.
• 46:11I'd like to hear opinion from
• 46:14Sabrina what's been your strategy
• 46:16in terms of managing high risk,
• 46:19smoldering patients in your?
• 46:20Practice, thank you to tell you,
• 46:23I think that's an important question,
• 46:25and obviously one where
• 46:26multiple combinations are
• 46:27being studied. You know, I think with
• 46:30the data available on Lenalidomide
• 46:31or Lenalidomide, dexamethasone.
• 46:32I think I've still had some
• 46:35pause in terms of the lack of
• 46:37overall survival data available
• 46:38in terms of benefit, you know,
• 46:41I think it's important to acknowledge
• 46:43that our discussion of treatment in
• 46:45patients who are asymptomatic is is
• 46:47very much different than patients
• 46:49who have active or clinical myeloma.
• 46:51And so I think the importance of
• 46:54overall survival benefit is really
• 46:56important to include in that discussion.
• 46:58So I would say my practice has
• 47:01been to discuss the data available,
• 47:03including the trials that are
• 47:05looking at different combinations
• 47:07outside of Lenalidomide,
• 47:08but I would say in general I
• 47:11continue to observe most patients.
• 47:13Thank you, ultimately we do need to
• 47:16understand more about the biology of
• 47:18disease of each individual case to
• 47:20address the prevention of progression.
• 47:23Another question comes through the
• 47:25chat question for I would posit
• 47:27it to Doctor Parker.
• 47:28How would you view the sequencing and
• 47:31where should we position car T cells
• 47:34versus the bispecific antibodies?
• 47:36Given that the response rates
• 47:37are quite significant for both?
• 47:41Yeah, I think that's a very good question.
• 47:44Very difficult one to answer and also be
• 47:47interested to hear no cars take as well.
• 47:50You know currently we don't have any trials.
• 47:53Obviously comparing head to head
• 47:54car T versus the specifics and
• 47:57looking at the BI specifics that are
• 47:59against BC mayor targeting the CMA.
• 48:01They do have somewhat similar response rates
• 48:04an it's but I really think how we position
• 48:08him is going to come down to one safety.
• 48:11What is the cytokine release?
• 48:12What is the neurotoxicity in
• 48:14these agents and then two is?
• 48:16Can we move party to the
• 48:18outpatient setting with these?
• 48:20Engineer does know for discussed
• 48:21bites are a little bit maybe a little
• 48:24bit more user friendly I guess.
• 48:26Is there off the shelf versus the
• 48:28Carty has to be manufactured so also
• 48:31keeping in mind it may come down
• 48:33to one patient needs therapy now
• 48:35device specifics that are targeting
• 48:37other things besides BC MA did have
• 48:40activity in those patients who had.
• 48:42Why are car T so it is feasible
• 48:44that you could do party followed by
• 48:46a fight with a different targets.
• 48:48But again I think we need a lot
• 48:51more data know for what
• 48:53is your take.
• 48:53Yeah I think you're right.
• 48:55I think we're still early.
• 48:57Unfortunately it's hard to compare
• 48:58head to head these studies because
• 49:00some of these are off the shelf.
• 49:02Some of these need time so it's study to do.
• 49:05I think one thing to keep in mind is
• 49:08that bites you have frequent dosing,
• 49:10whereas Carty is at one time.
• 49:12Infusion so that's been
• 49:14attractive for patients.
• 49:15Also, it's important to remember
• 49:16that you know for bites you you
• 49:19need a good indulgence T cells.
• 49:21So it went in terms of sequencing.
• 49:23Someone were to sequence.
• 49:24You want to give some time if someone
• 49:27gets it Carty and they're getting one for
• 49:30depleting therapy in their progressing,
• 49:32giving them a bite is not
• 49:34going to be very useful.
• 49:36So waiting a few months for improvement
• 49:38in their in their counsel lymphocyte
• 49:40count would be important to remember.
• 49:42Although I know these patients
• 49:44are very sick and some treatment.
• 49:46Thank you Terry and no far another
• 49:49question from Doctor Gowda.
• 49:51In the with the advent of BCM a
• 49:54targeted drug conjugates antibodies.
• 49:56How do how do we select again BC MA targeted?
• 50:01Whether we propose using an antibiotic
• 50:03conjugates or at the CMA cart.
• 50:06I think to some of this
• 50:08you already alluded to,
• 50:10but any further comments?
• 50:16I again I think it's hard.
• 50:19I think whenever we choose a
• 50:21treatment for our patients,
• 50:23it's looking at the patient looking the
• 50:25disease and looking at the convenience
• 50:28and toxicities of the drug and an adjusting
• 50:30it to them individual preferences.
• 50:33Another question from Doctor Gorshin
• 50:35with the updated Griffin data,
• 50:37does this impact our decision upfront
• 50:39therapy for high risk disease.
• 50:41KRD reverses Dara RVD.
• 50:43I think KRD still remains a very powerful
• 50:46induction therapy with very good.
• 50:48Fresh listen with sustain standards
• 50:50with continued therapy off.
• 50:52Note when you look at the composition
• 50:55of patients in the trials,
• 50:57the port a trial had about 30% of
• 51:00high risk patients that they all
• 51:02equally benefited with Dara RVD.
• 51:04This is a face to randomization
• 51:07and there were 15% of patients who
• 51:10harbored high risk cytogenetic profile
• 51:12and in their forest plots of data
• 51:14which I didn't present in the slides.
• 51:17It appeared that as though higher
• 51:19risks are genetic profile patients.
• 51:22May not have experienced the same
• 51:24magnitude of benefit in terms
• 51:27of deeper responses,
• 51:29so I would say there seem to
• 51:32be equally potent regiments.
• 51:34My own.
• 51:35Practice preference has been KRD for
• 51:37high risk patients generally and this
• 51:40I hear from some other institutions as well,
• 51:43but again practice patterns very in
• 51:45more data on the long term follow up
• 51:48is needed from the Griffin trial to
• 51:51you know where we don't have yet the
• 51:54progression free survival benefit.
• 51:55Eras for the for the four day trial,
• 51:59we have significantly longer follow up,
• 52:01so I think both regiments could be
• 52:04used interchangeably depending on the
• 52:07practice pattern off the institution.
• 52:09One question from Doctor Gowda.
• 52:13At relapse, for instance,
• 52:15if a patient was previously exposed
• 52:18to anti BCM, a targeted therapy,
• 52:20what is the BCM? A expression?
• 52:23Has this been looked at in the literature?
• 52:26I would ask either one of the speakers,
• 52:29but perhaps more so so far.
• 52:32So I know they are looking at it.
• 52:35I I don't recall if they published it,
• 52:37but there's a lot of and they're
• 52:39also looking at Solomon Soluble.
• 52:41Be CMA in the blood, but I can't recall.
• 52:46What's published? Yeah,
• 52:48I don't believe there is
• 52:50any published data on this.
• 52:52To my knowledge.
• 52:53I know each individual company is
• 52:55conducting their Olalla Sideclick
• 52:56preclinical and correlative
• 52:58studies to examine this,
• 52:59but not entirely clear yet.
• 53:03So with that, I think we're
• 53:05a four minutes after the hour.
• 53:07Thank you for the excellent
• 53:09presentations. All of you.
• 53:11I really appreciate everybody joining.
• 53:13I hope this was an informative
• 53:15session and hope to see you all
• 53:17for the subsequent sessions of
• 53:19the ash highlights. Thank you.
• 53:22Have a great day everybody.
• 53:24Thank you for organizing doctors item.