Yale ASH 2021 Highlights: Lymphoma

March 21, 2022

Information

March 18, 2022

Hosted by: Dr. Scott Huntington

Presentations by: Drs. Tarsheen Sethi and Shalin Kothari

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00:00So the yield Cancer Center I
00:02wanted to welcome those attending
00:03as well as my participants here
00:05for the ash update on lymphoma.
00:08So my name is Scott Harrington
00:10lymphoma clinician as well as a
00:12health services researcher and
00:13I'm joined with Doctor Kothari.
00:15He'll be focusing on aggressive B
00:18cell malignancies and mantle cell
00:20lymphoma as well as doctor Taxin Sethi
00:22who will present some updates on
00:24Hodgkin lymphoma and T cell lymphomas.
00:27Dr Frost will be joining us
00:28towards the end to help lead the.
00:30Question and answer discussion.
00:36So I know many have been focused
00:38on COVID and would love to
00:40look forward into the future.
00:42But in terms of indolent lymphomas and CLL,
00:45my slides are actually mostly
00:47focused on on how to kind of
00:50navigate our patients through the
00:52COVID era with indolent lymphomas.
00:55He's in my disclosures.
00:59And when we think about
01:01approaching sealant on how,
01:02given the uncertainty that we are
01:04facing with the COVID pandemic,
01:05there's a few takeaways of historical
01:07data that really come to forefront of
01:10my mind when approaching a patient,
01:12and that's that.
01:13The improvement in progression free
01:15survival infrequently has translated
01:16to overall survival benefits for
01:18patients receiving first line treatment
01:20for in lymphomas very different from
01:22my colleagues will be talking about
01:24DLBCL and Ansel cell and Hodgkin,
01:26but in this situation where CL and lymphoma.
01:30This kind of association has been
01:33seen frequently and there were some
01:35updates showing out here at Ash.
01:37This was doctor Wack who presented
01:38the update on the Alliance study and
01:41this was a randomized randomized
01:43study comparing bendamustine rituximab
01:45to a brute model therapy or brute
01:49rituximab and this was an important
01:51study that really led to the use of
01:52front line of root nymph and many of
01:54our patients and that was based off
01:56of a really progression free survival
01:58benefit both in the model therapy.
02:00Farm as well as the route number toxin
02:02that Barm both had a hazard ratio of
02:051.36 in the updated median follow-up
02:07of 55 months that PFS benefit was
02:10was made to be quite impressive.
02:13Doctor William did a very nice job
02:15in terms of presenting updated PFS
02:18stratified by risk factors and CLL,
02:20but she also had this slide here,
02:22which was overall survival and so
02:23at a median follow-up of 55 months.
02:25Overall survival between the three
02:27arms was that really identical
02:29and it's important to note.
02:30Got to follow up for this analysis
02:33was locked at April 2020.
02:35Kind of right before the pandemic and
02:37so having both this data as well as
02:40the corresponding ACOG study that was
02:42FDR versus abroad number Tux map will be,
02:45I think,
02:45important in terms of overall survival
02:47and how we address our patients.
02:49When we think about indolent,
02:50non Hodgkin lymphoma is often in
02:53the use of maintenance is a hot
02:56topic and this is just a little bit
02:59dated data now of follicular pharma
03:02maintenance or following our chemo.
03:03This is a randomized study PRIMA study
03:06and this is the data at 10 years and
03:08what we see is that adding maintenance
03:10rituximab for two years certainly
03:12improves progression free survival type.
03:15The next treatment time to
03:17delay of cytotoxic chemotherapy.
03:20In pretty stark differences,
03:2110.5 years in median PFS compared to
03:254.1 for those without maintenance.
03:26But again,
03:27the overall survival in this patient
03:29population at 9 years was identical.
03:32So why do we think about that?
03:33As we move forward,
03:35is that our patients within
03:37lymphomas usually live for for years,
03:39often well over a decade,
03:41and if there's a new potential
03:43downside or new pandemic that might
03:46impact their long term survival,
03:48a focus of,
03:49I think of our management needs to be
03:51addressed in that in that situation,
03:53and so most of the data on concerns
03:56of differential impact on COVID in
03:58our patients has been mostly data
04:01from CLO. This was very nice work from the
04:03French innovative leukemia organization.
04:05From Doctor Bacchus in and what they
04:08looked at was just over 500 patients
04:11treated in 17 French groups in with
04:14CLL and they presented the antibody
04:17response to two vaccines of M RNA COVID
04:21vaccinations and what we see is about
04:2370% of patients that were treatment
04:26naive mounted antibody response compared
04:28to 60% that were treated prior but off
04:31therapy at the time of their vaccination.
04:33And that compared pretty favorable
04:35compared to the on treatments.
04:37Only 22% of patients that received
04:40on treatment vaccination mounted
04:42antibody response after two doses.
04:45When you look at what those therapies were,
04:48the vast majority of patients
04:50were on BTK continues BTK,
04:52and in those patients,
04:53just 22% of patients mounted antibody
04:55response after two vaccinations.
04:57If you're on Phenetics,
04:58monotherapy is about 50%,
05:00and if you run vanetta clicks along with
05:02either anti CD 20 or BTK inhibitor,
05:04there was really very minimal or
05:07no response in terms of human
05:10response to to vaccinations.
05:12Now you might think that we've
05:14moved beyond two vaccinations.
05:16We've done three.
05:16We've done 4 here in the United
05:18States from our patients.
05:19This data did look at patients that
05:21had no response to two vaccinations
05:23that then went on to get a third,
05:25just about 1/4 of patients will will
05:27respond to 1/3 dose, and again,
05:29most of those responses were seen
05:30in the treatment, naive CLL,
05:32or those that were off treatment.
05:34If you were on therapy,
05:36you had only about a 25% chance
05:38of mounting antibody response to
05:40three doses of vaccine.
05:44So that data really goes nicely with
05:46what's been reported at smaller
05:48institution studies here in United States
05:50have been published in the last year.
05:52What we really didn't have is a lot
05:53of data in other independent farmers,
05:55and so this was very nice data from Doctor
05:58Beaton from Australia that presented data
06:01looking at waldenstrom's patients as well
06:04as Flickr lymphoma patients in Australia.
06:06So smaller study only about 34 patients
06:10with follicular 37 with waldenstrom's about
06:121/3 of patients had been treatment naive.
06:16Many of those in follicular
06:18had had immunotherapy,
06:20including some that had just completed
06:22treatment a few months previously.
06:25BTK was quite common in the Waldenstrom's
06:28group and fairly representative
06:29population for our patients with
06:32follicular and waldenstrom's.
06:34Not only did they have antibody titers,
06:36but they also did some neutralization assays.
06:38I'm not going to present that data,
06:40but really there was strong correlation.
06:41So for antibody titers and neutralization
06:44correlated quite well and they also had some
06:47T cell acids that I'll present at the end.
06:50This is just the antibody titers for patients
06:53that had in a chemotherapy compared to
06:56treatment naive compared to healthy controls.
06:59And really the treatment naive.
07:00Whether you had waldenstrom's
07:02or for lymphoma,
07:03their antibody titers were very
07:04similar to the healthy controls.
07:06But if you were getting
07:07immunochemotherapy within six months
07:09of completing immunochemotherapy,
07:10there was really significantly reduced
07:12antibody titers and they had very few
07:14patients getting a bit of tourism.
07:16But it did look like that response
07:18or reduction in antibody titers
07:20persisted quite far.
07:21They had one patient that was 21.
07:23Months out from finishing up in
07:24a tourism map that still did not
07:26mountain antibody response.
07:29This is there kind of a snapshot
07:31of their functional T cell assays,
07:33and So what they had was
07:35peripheral blood mononuclear cells,
07:37pre vaccination and then post
07:39vaccination and revaccination there.
07:41Really there was no stimulation
07:43of the T cells when these T cells
07:46were subjugated to COVID peptides.
07:48But in all patients which was encouraging,
07:52they did see signs of activation in
07:54the post vaccination and so this
07:56data suggested that these patients
07:58with Wellness drums and flick.
08:00At least have some T cell education
08:02with the vaccination.
08:06So just to kind of summarize,
08:08both the the ASH presentations but
08:10also kind of the the growing data into
08:13lymphomas in CLL and COVID is that
08:16patients with indolent lymphomas,
08:18particularly CLL at baseline,
08:20have lower human response to COVID
08:22vaccinations compared to healthy controls.
08:24Despite I think limited and
08:26relatively mixed T cell data,
08:28there really is very little downside
08:29of giving our patients vaccinations,
08:31and so all vaccine.
08:32All unvaccinated patients that come
08:34through your office with these diseases.
08:36Need to be cancelled every time you
08:38see them to really educate them to
08:40try to get them vaccinated and then
08:42even in those that are vaccinated,
08:44the vaccine itself,
08:44I mean actually not be producing
08:46a huge amount of protection,
08:48and so I'm having discussions
08:50about precautions and having
08:52discussions about use of prophylaxis,
08:54including heavy shelter here at Yale.
08:56We have this heavy shield COVID
08:58prophylaxis panel order set that is
09:00quite helpful in will kind of walk you
09:02through getting every shell to our patients.
09:05I also think it's important
09:06to recognize that.
09:07Treatments used for our diseases.
09:09Skeletal infamous likely have
09:10differential impact on human
09:12response to color vaccinations.
09:14Not surprisingly,
09:15anti CD 20 can really lead to low antibody
09:19titers after vaccination for 6:12,
09:21perhaps even longer.
09:22It is important to to kind of think
09:25about and then also maybe more
09:27surprising was the use of BTK so
09:28people in Bteq seem to have lower
09:30responsive to go vaccinations as well,
09:33and so because to this all of our
09:35patients with CLL and lymphomas
09:36really need to be educated about.
09:38Early identification of COVID
09:39illness as well as perhaps using
09:41outpatient treatment strategies.
09:43Monoclonal antibodies,
09:44antivirals, I think,
09:45actually,
09:46that is a key take away for managing
09:49patients with CLL and lymphomas these days.
09:54So there's going to be a couple studies.
09:55Hopefully reading out this later
09:56this year that will help give us a
09:58little more information about our
09:59patients that are immunosuppressed.
10:01The melody study is a massive
10:02valuation of lateral flow immunoassays
10:04and detecting antibodies to SARS,
10:06Co V2 and this is a large
10:08community based study in the UK.
10:10So about 35,000 patients were
10:12enrolled and they're going to
10:13be looking at antibody response
10:15to three and four doses of M RNA
10:17vaccine and then really importantly,
10:19they're going to look at whether the
10:21lack of antibody response correlate's
10:22with the risk of COVID-19 infection.
10:24As well, severity of disease.
10:26There's also an important study
10:28for our patients with CLL BTK'S,
10:30which public Tribeca study.
10:31This is out of Australia,
10:32where they're basically going to stop
10:35patients on their BTK temporarily
10:37vaccinate them with different
10:38strategies in terms of holding the BTK,
10:41ideally to identify ways of allowing our
10:44BTK patients to Mona a nice antibody
10:47response following vaccination against Kovan.
10:50So, given this uncertainty,
10:51given the fact that our patients
10:53typically do very well with a
10:55current modern therapeutics,
10:57I've generally recommended fixed duration
10:59without maintenance for most of my patients,
11:01and so when we think about fixed duration,
11:03lack of maintenance,
11:04was there any studies that ash that
11:06might influence our therapies going
11:08forward and there certainly were,
11:10and I'll focus on those in the
11:12next few slides.
11:13So this was an important study
11:15presented by Doctor Eickhorst,
11:16which was a CLL 13 study.
11:19This was a large randomized European
11:21study where patients without deletion,
11:23segmenting P without TP 53
11:28mutations were randomized either
11:30to standard IMMUNOCHEMOTHERAPY FC
11:32RVR or Vertex magnetic locks.
11:35Or the triplet venetoclax
11:36of Britain have been,
11:37and I've been a choose him out.
11:39Standard dosing so patients
11:40got six months of anti CD 20s.
11:43They got 12 cycles of venetoclax
11:44and then for Brewton if if people
11:46were still under deposit.
11:47If people could get up to 36 cycles.
11:52So the primary outcome was a.
11:54It was a 2 coprimary outcomes MRD,
11:57undetectable rate of 15 months,
11:58as well as PFS. Not surprisingly,
12:01with this kind of early follow-up that
12:03PFS has interim that's assessment hasn't
12:04been reached and so that's still to come,
12:07but they didn't have the 15 month MRD
12:09data that they presented at Ash and what
12:12we see here is that the peripheral blood
12:15flow cytometry based undetectable Mardi
12:17was 86% in the jivan arm and 92.2%.
12:22Can be tripled arm both the
12:24community therapy as well as RTX.
12:26Magnetic locks had lower around 50%
12:29and overall this there was two positive
12:31alarms compared to the immunochemotherapy.
12:34Both the G Ven and Gebruik infinite clocks.
12:38There was a kind of companion MRD
12:41assessment presentation which I think
12:43was was was quite interesting where
12:45they looked at MRD by the CLL molecular
12:49phenotype and what we can see here is
12:52that the molecular subtypes of seal
12:54that typically do much better with a
12:56brute compared to immunochemotherapy
12:58do better on the trip with the arm.
13:00So patients that are 11 Q patients
13:02that are unmutated have at least kind
13:04of a 1010 absolute percent increase
13:07of them are deemed detectable.
13:09With the triplet compared to the double
13:11ARM patients that have the lower risk
13:14disease in terms of being IG HV mutated
13:16seem to have relatively similar energy rates.
13:19Whether you get the doublet or the triplet.
13:23This energy does come at some
13:25toxicity in terms of the triple
13:26arm compared to the double it,
13:27and so things like febrile neutropenic
13:29infections were higher in the
13:31triplet compared to the doublets.
13:32And then when you add a brute
13:34nib you also saw a low rate,
13:35although it was there at
13:372% in terms of eight Feb.
13:40So in terms of the summary, and take
13:42away was that in terms of MRD status,
13:45the advantage choosing venetoclax
13:48were superior to chemotherapy and
13:51there was two arms that met their
13:53Co primary endpoint Rituxan Venetic
13:55LEX was not superior in terms of
13:57MRD of detectable rate compared to
14:00the primary FCR chemotherapy arm.
14:01They were very happy to see that most
14:03patients tolerated treatment well.
14:05There was very low rates of
14:08discontinuation and although there was.
14:10Some increased,
14:10perhaps toxicity for the triplet in terms
14:13of infection in terms of pepperoncini,
14:15and generally people tolerate
14:16this this regimen as well.
14:20So if we think about kind of the
14:22majority of patients are older,
14:23perhaps have comedies,
14:25maybe the triplet is is is not
14:28appropriate for that patient population.
14:31Is there another fixed duration
14:32regimen that we might be able
14:33to use in the near future?
14:34And there is?
14:35This is the GLOBE study and this
14:37was a randomized trial of patients
14:40that were older or those that
14:42were younger with committees,
14:44about 210 patients or so were
14:47randomized to either have been a 2.
14:49I take that back.
14:50They are brute NIM,
14:51so a brute in bleeding for
14:53three months and then a brute
14:54in Veneta clicks for toy cycles
14:55and then everyone stopped.
14:57It was not MRD directed therapy
15:00and then the old control arm.
15:01Here is a bit mad with crab.
15:05This is the PFS data.
15:07This data has been presented earlier
15:09EHA and what the focus of this
15:11abstract was was really on them
15:13or D rates in this in this arms,
15:15so we can see sphere.
15:16Certainly clear superiority in that PFS
15:19benefit of the approvement phenetics
15:22arm compared to Carnival in two,
15:24with a median follow-up of of 34 months,
15:26although overall survival
15:27was actually down tickle,
15:29and it'll be important to see the
15:31long term follow up from this.
15:32This study as well.
15:35That instead of being flow,
15:36they used NGS a little bit more sensitive
15:39and a little bit more reproducible.
15:41And what we see here is that
15:43the rates of them are detectable
15:44with this doublet oral double.
15:46It was about 50% in the peripheral
15:49blood as well as develop Mira,
15:51and that was statistically significantly
15:53improved over claim Bissell.
15:55And it's also notable that the
15:58concordance of bone marrow to
16:00preferred blood MRD was much
16:02higher in the doublet arm compared
16:04to the immunochemotherapy.
16:06A pharmacy.
16:09For patients that I think are thinking
16:11about PFS and how long they're going to
16:13be in remission after stopping treatment,
16:15I think this was a really important
16:17key addition of the study,
16:18which was everyone stopped a therapy in at
16:22certainly about 30-30 months of follow up.
16:25Here you can see that patients that
16:27were still in more detectable at the
16:29time of stopping therapy maintained
16:31a response without progression,
16:33and so this was, I think,
16:34important finding moving forward.
16:38And together with GLOW study as well
16:40as other phase two studies captivate.
16:43For instance, it's possible that
16:45we'll see additional labels of doublet
16:47or or doublet later this year,
16:49and I would stay tuned to see
16:51whether that could be incorporated
16:52into standard practice.
16:55So when we think about flicking
16:56them from and fixed duration,
16:58we're really more thinking about the
17:00anti CD 20 in terms of maintenance
17:03Rituxan mount and this was an important
17:05update from Doctor Call from Washington
17:07St Louis of the Resort study.
17:09So this was a randomized study
17:10done here in the United States.
17:12Patients had low burden of silicone
17:14phomma they all received four
17:15weekly doses and Rituxan mab
17:17and then they were randomized.
17:18If patients had a stable disease or
17:22better in patients either got rituximab.
17:25Monotherapy every three months,
17:26indefinitely until progression or
17:28they were on active surveillance
17:30with re treatment with rituximab and
17:33this was a one to one randomization.
17:37This data was originally published in
17:39JCM 2014 and the conclusions are here
17:42where basically Rituxan every treatment
17:43was as effective as maintenance.
17:45Rituximab for treatment failure.
17:47However, the main instruction
17:49map did delay time to needing
17:51cytotoxic chemo and ultimately,
17:53as you might expect,
17:54there was more rituximab used in
17:56the maintenance compared to the
17:57retreatment arm a year later.
17:59They followed up on quality of
18:00life and there was really no
18:01difference between the maintenance,
18:02rituximab norm compared to the
18:04retreatment and based off of
18:06this kind of earlier follow up.
18:08Doctor Colin,
18:08his colleagues recommended that re
18:10treatment rather than maintenance or tuck.
18:12Seemab was the preferred strategy.
18:15So now at around 10 years of follow up,
18:17do we have any different signals
18:18here and so this was freedom from
18:20first sent a toxic chemo and with
18:22long term follow up we still see a
18:25separation of the curves between
18:26Rituxan and maintenance continuously
18:28compared to the RE treatment strategy.
18:31You also see improved duration of
18:33response and so 66% of patients
18:35treated the maintenance or tux mab
18:37do not have progression compared to
18:40just 30% of patients treated with four
18:42doses of Rituxan have actually so much lower.
18:45Obviously need of Rituxan effort in
18:47in in administration Rituxan effort,
18:49the retreatment arm.
18:52And then,
18:53importantly,
18:53despite improvements in and
18:55time to cytotoxic chemo,
18:57the the main kind of take
18:58away was that oral survival,
19:00transformation risk secondary malignancy
19:02seemed very similar between the arms.
19:05And so the long term follow-up conclusions
19:07really didn't change from doctor calls.
19:08Mind you know it is true that
19:10time to send a toxic therapy was
19:13improved with maintenance or toxic,
19:15but the glass was kind of half
19:17half full in the sense that 63% of
19:19patients treated with retreatment
19:21remain chemo free at seven years.
19:23The duration response was certainly
19:25better with maintenance or Tux Mab,
19:27but he'd argued that 30% of
19:28patients received just 4 doses of
19:30rituximab in never needed treatment.
19:31Again for 10 plus years.
19:33And because overall survival
19:35benefit was identical.
19:36The treatment the Rituxan every
19:38treatment strategy rather
19:40than maintenance remained the
19:41recommendation of these investigators.
19:45So where do we stand in the spring of 2022?
19:48We have wonderful therapies for
19:50for patients with CLL and Lynn.
19:53On Hodgman, Thelma and we have
19:55to recognize that our therapy is,
19:57although they're wonderful,
19:58are not currative.
19:59Patients typically derive, you know,
20:02decade plus long benefits.
20:03And historically they've been poor.
20:05Correlation of first on
20:07PFS with overall survival,
20:08meaning that we can we can salvage our
20:10patients if they relapse and because of that,
20:12must much of my focus has been mainly.
20:15Maintaining good quality of life
20:16and and safety in there of COVID
20:19and what that really means is that
20:21actress surveillance and remains
20:22the standard of care for those
20:24that don't have clear indications
20:25for lymphoma directed treatment.
20:27It means educating patients really ad
20:29nauseum about vaccinations and early
20:32COVID testing as well as therapeutics.
20:34And then it means if if we do need treatment,
20:36which certainly some do shifting more
20:38towards the fixed duration therapies.
20:40Ultimately, as we move forward,
20:42I think MRD is an important outcome.
20:45But I also think that things
20:47like I mean reconstitution,
20:48quality of life and non formal related
20:50mortality but really important key
20:52metrics as we look at the future
20:54readouts of clinical trials and
20:56so with that I will move over to
20:58Doctor Kothari who will lead us in
21:00our presentation of diffuse large
21:02B cell phone mantels on phone.
21:16Thank you Scott.
21:18So I'm going to present on.
21:21DLBCL and Mantle cell lymphoma.
21:23Ash 2021. Highlights and for DLBCL.
21:26I would like to focus on
21:29two frontline studies,
21:30one being a Polaris which has been
21:32hotly debated and discussed in various
21:35forums after it was presented as
21:37a late breaking abstract and then
21:39use of high dose methotrexate to
21:42reduce CNS relapse which was a big
21:47retrospective analysis that we'll
21:49discuss in mantle cell lymphoma.
21:51I'll discuss.
21:51From the front line, long term data on MCL.
21:54One younger trial,
21:56which is which uses hydro site urban
21:59containing regimens compared to R
22:02Chop and then in maintenance setting.
22:04Use of R-squared which is limited
22:07with rituximab versus rituximab.
22:08After first line in elderly patients
22:11and then in relapsed refractory
22:13setting glue which is a bite.
22:16Bispecific T cell engager
22:17after we take a I failure.
22:22Here are my disclosures.
22:25So this was probably one of the most
22:30exciting trials that were, you know,
22:33discussed and presented at ASH 2021,
22:35which potentially changes
22:37our frontline care in DLBCL.
22:40And hence I would like to discuss this
22:43so there's a bullet is alive with Odin,
22:45is an antibody drug conjugate which
22:48targets CD79-B and eventually leads to
22:52microtubule disruption and epic ptosis.
22:55And you know it was.
22:57It has been extensively studied and
23:00now approved in combination with.
23:02In the relapsed refractory setting.
23:06So the researchers here studied
23:10patients who were previously untreated,
23:12had done previously untreated
23:14DLBCL age 18 to 8 years.
23:16IPI score of two to 5 = 0 to 2.
23:22With stratification factors
23:23as mentioned here.
23:25Randomize one to one between
23:27Polar archip versus R chop.
23:29So when Christine was swapped
23:31with a political map, dowtin.
23:34And it's important to note that it is
23:36a randomized double blinded study,
23:37so the investigators or patients had no,
23:40I did not know what therapy
23:43they were receiving.
23:45And this was followed by
23:46two cycles of rituximab.
23:47This was mainly to satisfy European
23:51regulatory requirements as eight cycles
23:54of therapy is a standard in Europe.
23:58The primary endpoint was
23:59progression free survival,
24:00which was investigator assessed.
24:02Secondary endpoints are listed here.
24:07And these were the demographic and
24:09clinical characteristics at baseline,
24:10so you know it's very well balanced.
24:13The important things to note here
24:16are there are 10% of patients
24:18with early stage disease and 90%
24:21with stage three or four disease,
24:24and IPI score of two was in
24:28approximately 38% of patients
24:30versus 62% were three to five,
24:33and it was well balanced between ABC and.
24:37Subtype, interestingly,
24:38there were double expressor lymphomas
24:41quite heavily represented,
24:4338% versus 41%,
24:46and double hit lymphoma or triple in
24:50lymphomas were 8% and 6% respectively.
24:55So these are the curves,
24:57the number one being investigated as
25:00assessed progression free survival,
25:02which was the primary endpoint of this trial,
25:05and the hazard ratio was of 0.73 not
25:09crossing one with P value of 0.02,
25:12showing statistical significance of
25:15polar chip in comparison to our chalk.
25:20If you if you see here the overall
25:23survival then you clearly there is no
25:25overall survival benefit at at at the
25:28short term follow-up so far with a P
25:31value of 0.75 and hazard ratio of 0.94.
25:37Interestingly, this is is assessment
25:39of patients who received subsequent
25:42treatments after this frontline therapy.
25:44And clearly if you count
25:46any modality of treatment,
25:48then our top armed patients
25:50got substantially more.
25:5230% of patients got received.
25:55Subsequent treatments versus
25:57only 22.5% in polar artship.
26:02This is the subgroup analysis and I
26:04would like to draw your attention,
26:06although we would you know caution in making
26:09any too strong of conclusions here, but.
26:14Monkey disease if it was absent
26:16at polar Chip, showed more
26:18statistically significant advantage.
26:20ABC seller Origin, you know,
26:24pull our chip bit better in that
26:28and IPI score of three to five
26:31versus 2 polar chips seem to
26:33do better in those subgroups.
26:39Common adverse events.
26:40This is, I think, a very important slide,
26:42because this really tells us that the
26:45double blinded portion of the study
26:47worked well because it's identical
26:49between polar chip and our chop,
26:51including peripheral neuropathy incidents.
26:53There was slight higher rate of
26:57higher grade febrile neutropenia
26:58in polar archip versus R chop,
27:01but the rest of the side
27:02effects are pretty compatible.
27:06So the way I see this trial is
27:08very nicely depicted in this figure
27:10from a cancer cell paper published
27:13recently by Doctor Chu is essentially
27:16a patients who are at have higher
27:20IPI score in the current setting.
27:22They would get our chop and when they
27:23fail they would be in this pool to
27:25get autologous stem cell transplant
27:27or they would have failed and they
27:29would have gotten a salvage regimens.
27:31In the future we would re stratify
27:34them based on their IPI score.
27:36I remember that 225 was the
27:38inclusion criteria,
27:38subgroup was for the three to five,
27:40showing more advantage,
27:42but all you know the inclusion
27:46criteria was two to five.
27:48And then you would basically give
27:50our choppin lower IPI score.
27:52Patients and polar ship in the higher ones,
27:55and then you would have less patience.
27:57Who would relapse and the ones
27:59who would relapse.
28:00You have now options of autologous
28:02stem cell transplant if they
28:03have relapsed after 12 months,
28:05or they have achieved complete remission
28:08from salvage regimen or car T cell therapy,
28:12and if they fail then to move
28:13on to salvage regimen.
28:15So this way we hope that we
28:17have less patience.
28:18In this pool to treat.
28:24So my final thoughts on the politics
28:26trial is that PFS benefit from a well
28:29designed randomized control trial
28:31in this population is meaningful.
28:33Regulatory approval is pending.
28:36Currently, long term data will guide
28:38further use subgroup analysis is only
28:41hypothesis generating no known biological
28:43rationale for higher responses in ABC.
28:46DLBCL is known so far.
28:48What will be the role of polit ISM and we
28:50wrote in and relaxed refractory DLBCL.
28:52Uh, because we all use polar,
28:55quite commonly in relapsed
28:57refractory setting as salvage,
28:59and that is going to become a problem
29:02once polatuzumab wrote in moves frontline.
29:05The good news is that we have
29:07other approved therapies like Tafel
29:09in and Lanka struck some AB,
29:11so hopefully we'll have more approvals
29:13in the future and we can expand our
29:17relapsed refractory repertoire.
29:18While the differences are statistically
29:21and clinically meaningful,
29:22this is not a game changer.
29:24Other class of drugs like bites and
29:26car T cells should and are being
29:28studied in frontline,
29:29especially in high risk disease.
29:32Financial toxicity is real and
29:34should be discussed with patients
29:36on a case by case basis.
29:402nd is hydro methotrexate is not associated
29:43with reduction in CNS relapse in patients
29:46with aggressive B cell lymphoma and
29:48international retrospective study of
29:512300 patients presented by Doctor Lewis.
29:56So we know that CNS IPI score is helpful
29:58in knowing what kind of patients are
30:01going to have a CNS relapse at are
30:03at a higher risk of CNS relapse.
30:06But overall patients with those high risk
30:10features they fare poorly and much needs
30:14to be done to prevent these relapses,
30:18so there is no consensus on what CNS
30:21directed prophylactic therapy should be
30:24given and how it should be incorporated.
30:26Into the systemic therapy backbone.
30:30Many centers, including Yale,
30:32we we have used hydro methotrexate,
30:34which we hope mitigate CNS risk
30:37based on some retrospective studies.
30:39In the past there is no prospective
30:41data to guide our treatment.
30:43So this eligibility criteria was
30:45patients with CNS IP S score of
30:48426 high grade B cell lymphomas,
30:50where we automatically give
30:52CNS prophylaxis therapy,
30:54primary breast or testicular DLBCL with the
30:58rest of the inclusion criteria shown here.
31:01Including exclusion being CNS
31:04involvement by lymphoma at diagnosis.
31:092300 patients were enrolled and.
31:13Almost 2000 to 1800 patients did
31:15not get high dose methotrexate
31:16versus 400 patients got high dose
31:19methotrexate and out of those patients
31:21who got high dose methotrexate,
31:23CNS relapse was observed in
31:2631 patients which is 8%.
31:31Just to draw your attention to
31:34the fact that really it was,
31:37you know, but it percentage wise,
31:40well balanced study including the E,
31:44COG and B symptoms.
31:47And external sites,
31:48which was of course heavily heavily
31:51represented in high dose methotrexate group.
31:54Here I would like to draw your attention
31:56to the high risk extranodal sites.
31:58So clearly we have more representation
32:00of those patients in the high dose
32:03methotrexate group as we would have
32:06expected and in as you go higher
32:08up in the number of external sites
32:10you have high representation in
32:12the high dose methotrexate group
32:14as we would have expected.
32:17These these are the results,
32:18so in all patients,
32:20cumulative incidence of CNS relapse
32:22was not statistically significant
32:24between these two groups.
32:27It shows 9.2% in Hydros method exit
32:29group and eight point 1% in in patients
32:33who did not get high dose methotrexate.
32:36The similar results hold true
32:38for patients who achieved CR,
32:40so this is a subgroup analysis.
32:46And this is the site of CNS relapse,
32:48which I thought was very interesting.
32:50So patients who did get high dose
32:53methotrexate they saw less of
32:55parent kaimal relapse versus they
32:57saw higher leptomeningeal relapse.
32:58So that brings into question
33:00whether a dual strategy of high
33:02dose methotrexate with intrathecal
33:03methotrexate would be appropriate.
33:05Although there is no data to support that.
33:11And then the group describes
33:13multiple subgroup analysis based
33:15on number of external sites.
33:17Specific external site involvement,
33:19CNS IPI score and the dosage of high dose
33:24methotrexate and so on and so forth.
33:26But none of these subgroup analysis showed
33:28any statistical or clinically meaningful
33:30difference between the two groups.
33:39So in conclusion, in the largest
33:41study to date, investigating
33:42efficacy of high dose methotrexate.
33:46In reducing CNS relapse in high risk
33:48patients, high dose methotrexate was not
33:50associated with reduction in CNS relapse.
33:52In overall, for patients within
33:54CR or in any high risk subgroup.
34:00Up next I would like to move to
34:04mantle cell lymphoma and discuss
34:06addition of hydro site therapy into
34:09immunochemotherapy before autologous
34:10stem cell transplantation in patients
34:12aged 65 years or younger with MCL
34:15known as the MCL one younger study.
34:19497 patients were randomized between control,
34:22which is our chop and experimental group
34:24being our chop alternating with our dehab,
34:27which can contain Sitara green.
34:31The results in which were initially 1st
34:33results published in 2016 are shown here,
34:36which I'm going to skip over.
34:39The updated results from 2021 are shown here,
34:44so you see that there is significant
34:46difference between the site urban
34:48containing regimen versus our chop.
34:50With trying to treatment failure
34:538.4 years in our dehab arm
34:55versus four years in our chop.
34:59Similar results hold true for in PFS,
35:03looking at from randomization from end of
35:07induction and from a stem cell transplant
35:10and you know this is very striking.
35:13To note that eight years was the
35:16median PFS in our chat party help arm,
35:19which is quite significant.
35:24Overall survival when you look at all
35:27comers and intention to treat population,
35:30there was no statistically
35:32significant difference.
35:33But if you stratify them by nippy
35:35then there was statistical least
35:37significant difference with hazard
35:39ratio of .74 not crossing the midline.
35:45And these are the highest highest subgroup
35:48stratification curves for all survival.
35:51So here you have high
35:52risk in defined by high,
35:53intermediate or high MIDI score.
35:55High High P53, MHC or BLASTOID variant,
36:00and versus low risk where you
36:03have no statistically significant
36:05difference between the two parks.
36:08So conclusions are that hydro site have
36:10been containing induction and autologous
36:12stem cell transplant achieves 60%.
36:1660% survival at 10 years
36:18with acceptable toxicity.
36:20Benefits of hydro cytarabine in
36:22high and low low risk patients.
36:24Was observed was significantly
36:26improved when adjusted to 67.
36:29Open questions still remain.
36:31Salvage treatment in art shop
36:33patients and avoidance of TBI
36:36may reduce rates of secondary
36:38malignancies in in both arms.
36:44Next, I'll quickly discuss rituximab,
36:47a little mild maintenance,
36:49superior to rituximab maintenance after
36:51Firstline Immunochemotherapy in MCL,
36:54which was the R-squared,
36:56elderly Merle clinical trial. Uhm?
37:02And, uh, another abstract
37:04from the same trial.
37:07Looking at MRD and its prognostic
37:10value in the same trial.
37:12So this trial randomized 620 patients
37:16between control arm where 312 patients
37:20got our chopped versus cytarabine
37:22containing regimen which incorporated art
37:25shop alternating with hydro cytarabine.
37:28And then there was second randomization
37:31for patients who achieved a CR.
37:34Between R&amp;R squared maintenance.
37:39So I'm not going to go over
37:41these patient characteristics.
37:42They are well balanced in both
37:45the arms and same thing holds true
37:48for the maintenance arm as well.
37:51These were the safety profile differences,
37:54quite significant blood and lymphatic
37:56system disorders were observed
37:59in R-squared versus hour and not
38:02unexpectedly higher grades of neutropenia,
38:05anemia and infections were
38:07observed in the R-squared arm.
38:10Well, these are the PFS and OS curves.
38:13There was no OS difference between the two.
38:15While there was a higher PFS
38:18benefit in the R-squared arm.
38:21What I found most interesting was the
38:24MRD analysis on in on this set of
38:28patients where we found paradoxically
38:30improved PFS in the R-squared arm in MRD
38:35negative patients versus MRD positive.
38:38The difference is quite striking
38:4161% versus 84%.
38:44So the conclusions are,
38:46I think,
38:48mainly that there is an MRD
38:50below the detection threshold of
38:53the currently used technique.
38:55Clearly,
38:55since there was improvement in
38:58the experimental arm which added
39:00in negative patients,
39:02so we have to take murded studies
39:05and you know analyze them carefully
39:09before making any big conclusions.
39:12Lastly,
39:12I would like to show a couple
39:14of slides on to fit the map.
39:15A step up dosing in relapse,
39:18refractory mantle cell lymphoma
39:20who had paid failed priority care
39:22therapy presented by Doctor Phillips.
39:25Blue Phantom AB is a 20CD3 bispecific
39:29antibody engager with two is
39:3121 configuration as shown here.
39:35This was done in combination
39:38with obinutuzumab.
39:39Either invest fixed dozing or step up dozing.
39:42What I want to draw your attention
39:44to is most patients.
39:4669% of patients had relapsed after
39:50therapy and many of these patients
39:53were refractory to prior therapy.
39:5690% of them including refractory
39:58to first line therapy.
40:00In half of the patients.
40:03Serious adverse events were
40:06observed in in this small study,
40:09including 62% of patients,
40:12most of them being related to Blue Fit map.
40:15But important to note that no
40:18adverse events leading to treatment
40:20discontinuation were reported.
40:22And these are the adverse events.
40:26Cytokine release syndrome
40:27being the most common one.
40:30This is why I thought of
40:32presenting this trial here.
40:33Very high CR rates and over our
40:38rates 67% in all patients and CR
40:42versus 81% overall response rate,
40:46especially in patients who
40:48have received prior therapy.
40:51So we believe that bytes bytes
40:55specific bispecific T cell engagers are
40:57going to play an important role in.
41:00Refractory mantle cell lymphoma
41:02in the future.
41:03Thank you and I'll pass on
41:05to Doctor Kirschen Sethi,
41:07who will present in Hodgkin
41:09lymphoma and diesel lymphomas.
41:14Hi everyone, while I'm
41:15trying to share my slides.
41:17Thank you so much for joining us.
41:35Alright, so I'm going to.
41:37I have no relevant disclosures.
41:38I'm going to start with Hodgkin lymphoma.
41:41My intention is to do a
41:43very broad overview of.
41:46Where the field is moving and
41:48both of these topics are.
41:50That is Hodgkin and T cell lymphomas.
41:54So first we'll start with some
41:56frontline trials in Hodgkin
41:58lymphoma and then moving on to
42:00some relapsed refractory trials.
42:02I think it's just important to note that
42:04all of these are basically checkpoint
42:06therapy based studies that I had I have.
42:10Included here,
42:11as you can see here,
42:14you know checkpoint in a better
42:16therapy is being brought into the
42:18frontline in Hodgkin lymphoma.
42:19In the in the hope of improving long
42:23term outcome while reducing toxicity and
42:26then at the same time you we also have.
42:30You know, relapse refractory.
42:33Specially the population that
42:35relapses post autologous stem
42:37cell transplant and there is a,
42:40uh, a need for.
42:42Therapy in patients who fail
42:44both been tax map and checkpoint
42:46inhibition in that line,
42:48and so that's where some of
42:49most of these studies are.
42:53That's the the the therapy they need
42:56that these studies are addressing.
42:58So first the frontline of the
43:00study that I'd like to mention
43:02is the by Doctor Alan at Emory,
43:06and this was looking at
43:08single agent pembrolizumab.
43:09I've followed by avd.
43:11For classical Hodgkin lymphoma,
43:13so this is Brett.
43:15This particular presentation was an
43:18update from a prior ASH presentation
43:21where they had presented the primary
43:24endpoint that is the complete metabolic
43:26response rate by pet city initially.
43:28So the brief background of this
43:30study was that as we know, 9 feet,
43:3424.1 amplification is common in
43:37patients with Hodgkin lymphoma.
43:39And so this study by design was.
43:43You had the lead in pembrolizumab
43:45primarily to be able to get some.
43:48Correlated data for febrile alone
43:51in these patients and to be able to.
43:54Again, see what is it that is
43:58correlating with both response
44:01and prognosis in these patients?
44:03So this particular abstract was
44:06presenting the secondary endpoints
44:08of updated PFS and overall survival
44:11at around the 33 month follow up,
44:14and then also further correlative studies.
44:18So this as I mentioned it was
44:21sequential Pembroke followed by Avd.
44:24The after the initial PET scan 3 cycles
44:28of pembrolizumab was were given and
44:30then the second PET scan was obtained.
44:33At this point of time,
44:35the primary endpoint of complete
44:36of metabolic is complete.
44:38Metabolic response was assessed
44:40and then in addition they did.
44:44Correlative studies that included both
44:47immunohistochemistry as well as fish 9.
44:50P, 24.1 alterations.
44:51Then patients went on to receive a video.
44:57So as you can see here, the median age.
45:01For this patient, cohort was 29,
45:04but they did include patients
45:06up to 77 years of age and
45:08about 15% for elderly patients.
45:12They enrolled a total of 30 patients and.
45:1760% were advanced stage
45:19Hodgkin and 40% were early.
45:23Unfavorable Hodgkin.
45:25So on the top right of the
45:28slide you can see that.
45:31The there basically assessment of
45:34the complete metabolic response
45:36after three cycles of pembrolizumab.
45:38They defined a parameter called near
45:42complete medical complete metabolic response,
45:44which was defined as more than 90%
45:47in metabolically active tumor volume,
45:51and they found that nearly that CR,
45:54along with near CR was seen in
45:57about 63% of patients that embryo
46:00alone in the frontline.
46:04And the remaining patients
46:05had a partial response.
46:07In addition, they also looked at.
46:12At this time, they reported updated
46:15PFS and overall survival data,
46:17which showed 100% progression free
46:20survival as well as overall survival
46:23at a median follow-up of 33 months.
46:26In addition, there.
46:28This study was very well designed
46:30in terms of Correlators after the
46:32lead in Pember Lizum app and they
46:36noted that alterations of 1924.1,
46:39which they defined as either die.
46:41So my polysemy copy number gain or
46:44amplification was present in one sum,
46:47one form or the other in all of the patients.
46:51It's 100% of the patients
46:53that they had tissue on,
46:55which is 28 out of the 30 patients.
46:57And.
46:59In looking at a more the
47:03immunohistochemistry they calculated
47:04and age score which was combining
47:07the intensity and intensity of PDL 1.
47:11Staining along with the percentage
47:13of cells that were positive.
47:16And they compared both of these to
47:20the response to response between
47:22responders and non responders.
47:24And they did not find any correlation
47:26between PDF and pathway markers and response.
47:30So in conclusion, this.
47:35Was a pretty well tolerated
47:38regiment where no additional
47:40signal of safety was seen and.
47:44Their base they looked at long term
47:49into 33 month overall survival at PFS,
47:52which was both 100%,
47:54so it was fairly effective regimen,
47:57and along with that they did not find any
48:01correlation between the PD one pathway
48:02markers and the depth of response.
48:04So they basically they were.
48:06They implied that you could see
48:09favorable responses and even in patients
48:11who had low PD L1 positive ITI.
48:14So this combination and are now going
48:17to be studied in phase three trial and
48:21again one of the active combinations in
48:26frontline using checkpoint inhibition.
48:28I'm only going to briefly going to go
48:31through the concurrent Pembroke and DVD data.
48:34Again.
48:34This was frontline here.
48:36There was no lead in and this
48:38this was basically.
48:40I bought the drugs were given concurrently
48:43and one difference between the prior
48:45study and this was that this was
48:47primarily a safety signal study that
48:49was the primary endpoint and then the
48:51secondary endpoint was the CR rate.
48:55So in this particular.
48:58Study they assess response
49:00after two cycles of Pembroke,
49:03given concurrently with Avd and
49:06then depending upon the stage.
49:09Because this study included
49:11patients through all stages.
49:14If you look at the patient characteristics,
49:16it included patients that were
49:18stay as as early as stage one
49:21to stage through stage four,
49:23so the total number of cycles
49:25really depend on what the stage was.
49:28But since their primary endpoint
49:30was safety after two cycles,
49:32they and the main secondary endpoint
49:35was response after two cycles that.
49:40So that was assessed basically regardless
49:41of the total number of titles.
49:48So since the primary endpoint was safety,
49:51they showed that the main.
49:55Non habit illogical.
49:57Side effects that were grade
50:00grade three or four they were.
50:03Very minimal and in terms of
50:05immune related side effects,
50:07they had grade 3-4 transmitters,
50:11specifically the the one patient
50:13with grilled 4 transmitters.
50:15They had a concurrent use
50:17of over the counter CBD oil.
50:19It appears like so they it was.
50:22They were not sure whether it
50:25was truly drug related versus
50:26related to this CBD oil use,
50:29but and then there were a few patients.
50:32Three patients with grade 3.
50:34Transformers and all of
50:36those cases were reversible,
50:37so overall,
50:38this regimen was thought to
50:41be well tolerated.
50:45In, when the two when immune
50:48checkpoint inhibitor and
50:49chemotherapy was given concurrently.
50:52Their pet two CR rate,
50:53which was the secondary endpoint,
50:54was 66% in all patients.
50:58The overall response rate was 100%.
51:03They reported a median follow at a
51:06median follow-up of 16.2 months.
51:08They reported a PFS in overall survival of.
51:14So. Basically,
51:17the median was not reached and.
51:20The one year old also I was
51:23100% one year, PFS was 96%.
51:27I think one important thing that is
51:29important that is keep to both of
51:31these studies in the frontline is that
51:34immune checkpoint in a better use.
51:37Stand result in.
51:39So PET scans cannot are probably
51:42not as it's not as straightforward.
51:45How do you interpret PET scans in the
51:49setting of immune checkpoint inhibitors?
51:51And so it would make sense to look
51:55at novel things like there is.
51:58There are the lyric criteria for pet
52:00city in patients with immune checkpoint
52:03in a better doctor Alan study looked at.
52:08The total metabolic tumor volume
52:10in this particular study looked
52:12at circulating tumor DNA and the
52:15reported cases where the circulating
52:18tumor DNA was both more sensitive
52:20and specific measure of residual
52:22disease rather than pet city.
52:26So. In conclusion, this was
52:29a safe and effective regimen,
52:32again given in concurrently in the frontline,
52:35and again one of the ways that we we see
52:40checkpoint inhibition being incorporated
52:42into the frontline and Hodgkin.
52:45OK, so I'm going to quickly go through
52:48three relapse or practice studies
52:50that are looking at checkpoint
52:52inhibition combinations in relapsed
52:55refractory Hodgkin lymphoma.
52:57The 1st of this is using drugs.
52:59The Jack 2 inhibitor and this is
53:01based on the rationale that nine
53:04P 24.1 amplification results in
53:07amplification not only of the PDL 1
53:11PDL 2 pathway but also of Jack 2. And.
53:15So that was part of the rationale,
53:17and so they used a combination
53:22of nivolumab with ruxolitinib and
53:25they did a 3 doors, tested 3 doors,
53:28levels of regulator there.
53:32Again, this was the patient population.
53:34Here was checkpoint inhibitor
53:36refractory so that the patient had
53:38already progressed on a checkpoint in
53:40a bit or single agent therapy before.
53:44So the median age of all
53:46patients with 38 years and.
53:5032% of the patients had had a prior
53:54autologous stem cell transplant.
53:58So here they saw they reported.
54:02Overall response rate of
54:0548% and the CR rate of 24%.
54:11The total duration of response
54:14you can see here that there were
54:17several patients that were still.
54:20Had continued response especially.
54:26So especially those who had complete
54:29response with this combination.
54:45Sorry so. As you can see here,
54:48the they reported the PFS and
54:51OS said two years it was,
54:53which was were 46% and 87% respectively.
54:57In this multiple refractory population.
55:03Most side effects were grade one and two,
55:06and primarily consisted of him,
55:08hematological side effects
55:09as well as GI side effects.
55:13And the immune related side
55:15effects that were seen were
55:16mostly hepatitis and pneumonitis,
55:18and all these were reversible.
55:21So in the correlative studies,
55:23they looked at MD after insulating them.
55:26And. They found that there
55:28was decreased expression of.
55:32With the use of this combination.
55:36So overall this was again found to be a safe.
55:41Combination in multiplicity refractory
55:44population including basically all patients
55:46were checkpoint in a better refractory.
55:49So I'm going to pause here because
55:51in the interest of time. And.
56:05Hi, we're coming up to
56:06the hour and I know people
56:08want to use their one o'clock to
56:09perhaps get outside and do some of
56:11those nice weather. So there's two.
56:13I think questions that I have.
56:16Induction appreciate the same
56:18one I had which was to Torshin
56:21in terms of frontline Hodgkin.
56:23You know PFS ruling overall
56:26survival for that.
56:27That one analysis out of Emory shows
56:30really great with Checkpoint ABA VD,
56:32but we also have good data on BVD.
56:34How do how do you think we move forward?
56:37Do we have a study for that?
56:39Where are we in terms of
56:40addressing that question?
56:42So I believe that there is a.
56:46There is a frontline study that is
56:49looking at the comparison between those
56:51two that can help answer that question,
56:53but at this point it seems like so as far
56:56as this particular study was concerned,
56:58Pembroke followed by it
57:00did include bulky patients.
57:02What they found was that most of
57:04the patients were bulky disease.
57:06After three cycles of Femoro alone they
57:09had a near complete metabolic response,
57:11not necessarily complete metabolic response.
57:13That was kind of one of the differentiating
57:16features in that particular study.
57:17But at the same time,
57:18when it comes to immunotherapy,
57:19it's very hard to interpret a lot
57:22of the patients, like for example.
57:24Even in the second study,
57:25the pet 2 positivity did not
57:28correlate with early relapse.
57:30So the it's not the same as what
57:32we see with non immuno therapeutic
57:34agents like you can sometimes
57:36have long term responders even if
57:39they have initial positivity.
57:41So
57:41and then I guess the question is
57:43is sequential versus concurrent.
57:45Do you think we need a trial randomized
57:47trial to really address the the
57:49appropriate timing of checkpoint with avd?
57:53In the second study,
57:54I think the first study was more.
57:56The design was more to understand.
57:59It was a few years it was started a
58:01few years ago where we didn't know a
58:04lot about the correlated correlations
58:06for this particular for Pember alone
58:08and the efficacy of Pembroke loan,
58:10and that was the reason to do the lead
58:12in rather than the safety measure,
58:14since the second study is already
58:16telling us that there is,
58:17it's safe to do the combination.
58:18I feel like similar to what we do with BV,
58:21like AVD versus BB followed by avd.
58:25I feel like both of those can be
58:28reasonable options, it seems like.
58:31That's helpful, thank you and
58:32then the one thought I had before
58:34we open it up to the audience.
58:35If there's questions, please,
58:37please send them in was to Doctor
58:39Kathari in terms of the long
58:41term data from Nordic and and
58:43the study that you presented is
58:44anthracycline followed by hydac.
58:46Do you do that or do you use
58:48bendamustine with your induction?
58:50You know how do?
58:51How do you put that all together?
58:53Yeah, so there are multiple backbones
58:56that that have been studied,
58:58but I must admit that the most studied
59:02regimen, and now with this data,
59:04especially with you know high risk
59:06patients having a survival benefit would
59:09be our chop alternating with our dehab.
59:11But you know there is a Nordic regimen
59:14where you alternate art shop with
59:16hydro cytarabine and then you have a
59:19you know sort of more of a US regimen
59:21of Arminda alternating with our site.
59:23And again, these are all high doses.
59:26These macaroons have been studied
59:30and compared with each other but
59:31without the site are being part.
59:33So, for example,
59:34our chop was compared with our vendor.
59:36So we are extrapolating that you
59:38know our Brenda is better than
59:41our top end would be better even
59:43when combined with a high dose.
59:46Of course there are some early stage,
59:48you know,
59:48small patient series of prospective
59:51trials of doing of using our Bender
59:54alternative with our high dose side.
59:57So what all to to answer your question,
60:00there are multiple possibilities
01:00:01in frontline mantle cell lymphoma
01:00:03and we really haven't established
01:00:051 standard of care like we have in
01:00:08diffuse large B cell lymphoma and
01:00:10that's something it remains still a bit
01:00:12elusive as to what will we'll all use,
01:00:15but you know,
01:00:16I think it's it's a good problem to
01:00:18have where you know you can really
01:00:20customize therapy based on the patient,
01:00:22comorbidities and age and stratification.
01:00:27Thank
01:00:27you why we're over the hour and I want to
01:00:29thank all the attendees for joining today.
01:00:31Feel free to email each of us if
01:00:33you have questions about specific
01:00:36presentations we you know went over
01:00:38today and how we interpret that
01:00:39and how we approach our patients.
01:00:41We'd be happy to to engage over that,
01:00:43but enjoy your Friday and thanks for joining.