Lymphoid Malignancies

January 26, 2021

Information

January 22, 2021

Presentations by Shalin Kothari, MD, Francesca Montanari, MD, and Tarsheen Sethi, MD, MSCI

ID6125

To CiteDCA Citation Guide

00:00So today's will be the second part
00:03of our series about updates from
00:06the American Society of Hematology,
00:09with the highlights today focusing
00:12on lymphoid malignancy's.
00:15As you probably know,
00:17we have six sessions within this series.
00:19We had the myeloma session last
00:21week and this is actually has been
00:23recorded and available on the website.
00:26For those who could not attend last week,
00:29so feel free to check their website and
00:31we will also be including the slides
00:34for your own reference next week on
00:36January 29th will be the update on my
00:39load malignancy's February 5th will
00:41be pediatric leukemia and acute for
00:43plastic leukemia and pediatric oncology.
00:45February 12 will be the classical or
00:48benign hematology and February 19 will
00:50be cell therapy and transplantation.
00:52All of those are on Fridays and
00:55at 12:00 PM noon.
00:59All of those sessions will be recorded
01:01and the slides will be available along
01:04with the recordings after the sessions.
01:07There will be CME credit for those who submit
01:10for it at the end of the entire series,
01:13and they'll be a form for feedback
01:15where we would love to get your
01:17input about what you like and what
01:20you don't like about the series and
01:22how we can improve it going forward.
01:24This is the first time we're doing
01:27the hematology post ash highlights,
01:28and I hope to keep this going for
01:31the next few years with a combination
01:33of virtual and in person.
01:35Components, so for today's session
01:38it's a pleasure to have three of
01:41our faculty presenting and we will
01:44be starting with Doctor Schelling,
01:46Kothari or Assistant Professor of
01:49Medicine who will go over aggressive
01:52lymphoid malignancy's B cell type.
01:55Doctor Francis Commentary will
01:57cover for us the indolent B cell
02:00malignancies and Doctor Turchin City.
02:03Also Assistant Professor of
02:05Medicine will be covering.
02:08The T cell malignancies,
02:10both indolent and aggressive.
02:13At the end we will have a Q&A.
02:16The talks will be around 40 to 45
02:18minutes in total and the last 15
02:20minutes will have a question and
02:22answer session and this will be
02:23moderated by our Assistant Professor
02:24of Medicine Doctor Scott Huntington,
02:26who will be joining at the panel
02:28at the panel at the end.
02:30So without further ado,
02:32I'd like to introduce Doctor Schelling
02:33Kothari, who will start us off.
02:35Thank you.
02:38Thank you Amar.
02:44So today I'm going to talk about
02:47updates from Astronium 20 focusing
02:50on aggressive B cell informers.
02:52I'll cover for studies.
02:54One very heavily participated and we
02:57were one of the top accruing sites of
02:59oral triple combination of BTK number M,
03:02Tor inhibitor animite,
03:04and relapse refractory Richter's
03:06transformation and Dean over DL BCL and then
03:09I'll talk about more sooner to Zoom app,
03:12which is a T cell engaging bispecific
03:14antibody in aggressive lymphomas.
03:16I will not cover the other 3T cell
03:19engaging bispecific antibodies,
03:21but they were also presented at.
03:23Ash.
03:253rd would be the Lima MRD project
03:27in mantle cell lymphoma.
03:29An Lastly roll off CNS prophylaxis
03:31in high risk DLP CL.
03:35So this is the first study is the once
03:38daily ordered triple combination of
03:40the three agents that I talked about in
03:43Richter's transformation and in over
03:45diffuse large B cell lymphoma. This was
03:48presented at ASH 2020 by Doctor Mato.
03:53Other preclinical studies.
03:56This was a national combination based
03:59on synthetic synthetic lethality.
04:01As you can see on the left,
04:04the tumor volume of in mice drastic
04:07drastically reduced in the triple
04:10combination arm in comparison to
04:12the vehicle or a single agent.
04:15On the right you just see the B
04:18cell receptor pathway and other
04:21pathways that further help.
04:23In Onco Genesis an how the triple
04:26combination therapy could help prevent
04:28tumor resistance by targetting
04:30different pathways together,
04:31namely employment pathway AKT,
04:33mtor pathway, BTK pathway,
04:35and I have four inhibition.
04:41The key eligibility criteria for this
04:443 + 3 design is age more than 18.
04:48Life expectancy more than 12 weeks,
04:51with other standard inclusion criteria.
04:53The stage one, which is what we are
04:56presenting today is the BTK monotherapy,
04:59like not in combination in one
05:02pill but three separate pills of
05:05DRM 12 which is the BTK inhibitor.
05:08Novel became a bitter in combination with.
05:12Letter from Little Mind and
05:15everolimus and then eventually.
05:18We are will start accruing
05:20the Stage 2 instead of three,
05:22which is a single pill with
05:25three two different drugs,
05:26and then eventually all three
05:28drugs in one pill for patient
05:30convenience and ease of use.
05:35This is these other patient characteristics.
05:37Here you can see that in
05:40Richter's transformation panel,
05:41most patients had gotten our chop while in
05:44DLB seal all patients had gotten our job.
05:48So these patients were heavily treated.
05:50Median prior therapies were three in
05:52Victor's transformation into Indy.
05:54LBC, Elko hurt, so these were in general.
05:57The point is that they were
06:01heavily pretreated patients.
06:03At this is the data,
06:05so overall response rate in
06:07Richter's transformation is 46%,
06:09which is quite phenomenal in
06:11in such an aggressive disease,
06:13Indian over DLB sell, it was 45%.
06:18These are the CRN PR's.
06:23This is the waterfall plot,
06:25essentially looking at the
06:28percentage of tumor reduction.
06:31Yellow being the LBC, Ellen blue
06:33being Richter's transformation.
06:34You see that there is a significant
06:37tumor reduction in both the cohorts.
06:42Cytopenias were present for sure.
06:46Given the triple combination neutropenia,
06:4933% grade, 321% grade,
06:52429% Grade 3 thrombocytopenia,
06:54and 8% Grade 4 thrombocytopenia.
06:59The non heme toxicities were low.
07:02You know 4% odds are only in one patient
07:05and there were no grade for side effects.
07:11So the conclusion of this study was
07:14that the primary endpoint was met,
07:16that the triple combination therapy
07:18has an acceptable study safety profile.
07:20The main safety findings were expected
07:22and manageable, and currently we are
07:25accruing for the phase two study.
07:28It is underway targeting patients
07:30with novel agents exposed to relapse,
07:32refractory CLL and other non
07:35Hodgkin lymphoma's. Um?
07:38The next study I will talk about is
07:40the single agent motion resume AB,
07:43which is a T cell engaging bispecific
07:46antibody and this was presented by Doctor
07:49Adam Orlowski from Brown University.
07:51And this was studied in the
07:53frontline setting,
07:54so treatment naive elderly unfit patients
07:57with diffuse large B cell lymphoma.
08:01Up to 30% of patients aged more
08:03than 25 years do not receive
08:05standard chemo immunotherapy,
08:07so there is a lot of unmet need
08:09and there is need to develop
08:12therapies which are less toxic
08:14more sooner to some apples in IgG,
08:16one CD20 CD.
08:18Three bispecific antibody that
08:20redirects T cells to engage and
08:23eliminate malignant B cells.
08:25So here Doctor ourselves keep presented
08:27early clinical data with single agent
08:30most Natuzzi my best first line therapy.
08:32The key inclusion criterias,
08:34treatment, naive,
08:35ideal BCL,
08:36patients or high grade B cell informers
08:39for patients who were 60 to 79 they
08:42they would have to have impairment in
08:45adls or inability to tolerate full.
08:47Those immunotherapy for whatever reason.
08:50Just like with all other
08:52bispecific antibody trials,
08:53typically it's done in a ramp up
08:57fashion to decrease the chances and
09:00severity of cytokine release syndrome.
09:03Study design allowed pre face therapy
09:06with Prednisone and vincristine and
09:09responses estimates were done at interim
09:11cycle four in Cycle 8 and every six months.
09:15There are two doors.
09:17Levels are studied 13.5
09:19and 30 at the at day 15.
09:21So you start with one milligram
09:23to milligram in 13.5 or 1,
09:26two and 30,
09:27and then there was continued every 21 weeks.
09:32Patient population is shown here.
09:34So 29 elderly unfit patients were
09:36enrolled in this study of eight
09:38patients less than 80 years old.
09:40Five patients had impairment in
09:42renal function. As you can see here,
09:44performance status, you know 022.
09:47We do see clinically patients who
09:49have worse performance status,
09:51but given the clinical trial design,
09:53it isn't. It is quite understandable
09:55that they were enrolling 022.
09:58Quite a few. Almost 50% of Asia.
10:00With stage four disease and 50%
10:03with elevated elevated LDH,
10:05so overall a good real world
10:07characterization of patients here.
10:12Side effects were present,
10:14but relatively easy to manage,
10:16so rash, fatigue, abdominal pain,
10:19infusion related reaction,
10:20decreased appetite and dry mouth.
10:22Cytokine release syndrome was also present,
10:25but the grade three and four
10:28CRS events were very low.
10:32The best oral response rate was
10:36seen in in 6363.5% of patients
10:39and in the highest dose cohort,
10:4230 milligrams. 50% of the patients
10:46achieved complete response.
10:50This is still sure the
10:52durability of response.
10:53The ones in green are the
10:56patients with complete response
10:58and most of them continue to
11:00enjoy the durable response rate.
11:02Immediate duration of response
11:04was not reached and this is only
11:07a 5.4 months of median follow-up,
11:09so clearly very early data an we need
11:12to wait for the data too much or.
11:18So these are the authors conclusions
11:20early clinical data indicates that single
11:23agent is manageable and acceptable.
11:25Has acceptable safety profile.
11:27Encouraging efficacy was seen in this
11:29setting, an although they did some
11:31correlated studies and they did not find
11:34any clear Association with peripheral
11:37T cell activation and response.
11:39This paves way for either single agent or
11:42combination therapies with most senators.
11:44Mab in frontline setting,
11:46especially in elderly unfit.
11:48Patients.
11:48The third study I would like to
11:51talk about is the predictive power
11:53of early sequential MRD monitoring
11:55in mental cell lymphoma following
11:58autologous stem cell transplantation
12:00with or without rituximab maintenance.
12:04This was presented by Doctor Callanan
12:07on behalf of the Lisa Group.
12:09The study was designed as such so the
12:12patients with classical mantle cell
12:14lymphoma had baseline MRD analysis
12:17done followed by 4 cycles of our dehab
12:20followed by pre autologous tense,
12:22transplant,
12:22MRD analysis and then you know high
12:25dose chemotherapy and then again post
12:28autologous transplant MRD analysis and
12:30then patients were either randomized to
12:33trucks or maintenance or observation.
12:35That type of MRD that was done was.
12:39Yeah,
12:40so IGHQ PCR.
12:42Looking at VDJ recombination region.
12:47Am the only talk about the first name
12:49given in interest of time is the
12:51prognostic impact of MRD status pre
12:54and post autologous stem cell transplant.
12:59This is the survival curve for pre
13:01autologous stem cell transplant,
13:03MRD status, so the one in red is MRD,
13:06negative green, blue is MRD positive so
13:09you can see that there is clear split
13:12in PFS and OS with improvement in PFS
13:14and OS in patients with MRD negativity.
13:20And hence essentially,
13:21this figure shows that there is a
13:23prognostic value in in doing MRD analysis.
13:26The next question that the authors
13:28looked at was to look at impact of
13:32maintenance therapy and MRD negative
13:34patients so the one the curve in
13:36red is patients who got Rituxan.
13:38Mab were but were not MRD negative
13:41and in blue is patients who are an
13:44observation and were MRD negative so you
13:47can see that even though these patients.
13:49MRD negative that is a clear split and
13:52that is you know statistically significant
13:55difference with PFS OS benefit in
13:58patients who got rituximab maintenance.
14:01The same thing holds true
14:03for post autologous stem,
14:04cell transplant, MRD also.
14:06Hence, the data is a bit humbling.
14:09Where we would you know would love
14:12to use MRD for therapeutic decisions,
14:15but it is pretty clear that maintenance
14:18rituximab still remains gold standard
14:20in classical mental cell lymphoma and
14:23it's definitely a proof of concept
14:25that MRD is a good prognostic tool
14:27and should be used in addition to
14:30other tools such as pet imaging.
14:35Lastly, I will talk about CNS prophylaxis
14:37in aggressive non Hodgkin lymphoma's.
14:39There were two abstracts presented in the
14:43oral session at ASH 2020 and both kind of
14:46guide us in different directions in terms
14:49of what we do in clinics as of today,
14:52but there is a big caveat that both are
14:56retrospective studies and I would say
14:58that we need more prospective data before
15:02we change our or practice patterns.
15:05Traditionally, the CNS relapse risk
15:07is calculated as CNS IPI scoring,
15:10which includes age, ekach status,
15:13LDH, stage of the patient.
15:17The number of external sites and
15:20kidney and adrenal involvement.
15:22So patients who have intermediate
15:24or high CNS IPI score are thought to
15:28benefit from from CNS prophylaxis,
15:31mainly high dose Ivy methotrexate.
15:35Rather than intrathecal methotrexate.
15:39The first study that I'll talk about here.
15:43Their objective was to determine if high
15:46dose methotrexate reduced CNS relapse rates
15:49and this was based in Alberta, Canada.
15:51The design was retrospective include
15:54patients were 18 to 70 years of age with
15:59DL BCL treated between 2012 and 2019.
16:02These patients CNS involvement at
16:05diagnosis were excluded, as evident here.
16:10What is interesting is that at this
16:12site where they had identified
16:14high risk patients only out of 326
16:17identified high risk patients,
16:19only 115 had gotten high dose methotrexate
16:21for unknown reasons to under 911 patients
16:24did not get high dose methotrexate,
16:26so right off the bat you know since
16:29we are analyzing only 115 patients,
16:32it's difficult to make any
16:34strong conclusions.
16:35But here high dose methotrexate was
16:37used was associated with younger age,
16:40more the next one external site
16:42could bring additional involvement
16:44and double hit lymphoma.
16:47Multivariate analysis is shown here
16:50where you can see that the. There was no.
16:55Reflected high dose methotrexate did
16:57not show any improvement in CNS relapse
17:01and the same holds true for intensive
17:04immunochemotherapy such as our dose
17:06adjusted epoch or are high perceive.
17:08Add in comparison to R.
17:10Chop consolidative autologous
17:11stem cell transplantation was
17:13definitely showed more impact,
17:15although it did still cross the.
17:19Hazard ratio of 1.
17:22Here I'm showing multivariate
17:24analysis for PFS and OS.
17:27You can see that prophylactic high
17:29dose methotrexate and intensive
17:30immunochemotherapy did not show any
17:33statistically significant difference,
17:34although there was difference
17:36in PFS and OS in consolidative,
17:39autologous stem cell transplanted patients.
17:42Authors conclusions were there CNS
17:44relapse affect 6% of DCL patients and
17:47risk of CNS relapse or similar with
17:50or without high dose methotrexate and
17:52and as a proof of concept similar to
17:56rates reported in prior publications.
17:59Consolidative autologous stem
18:01cell transplantation or intensive
18:03immunochemotherapy trended to reduce CNS
18:06relapse of finding that is worthy of
18:09further study in a prospective setting.
18:12The other study that I will quickly go
18:16over before I hand over to Doctor said
18:19he is the CNS relapse by prophylaxis route.
18:23So the this study was a US multi
18:27center retrospective study where they
18:29found that from all the centers with
18:33patients 100 and 1000 patients total
18:365.5% had overall CNS relapse rate of
18:39the patients who got into tickle.
18:42CNS prophylaxis,
18:435.3% had CNS relapse and of the patients
18:47who got intravenous prophylaxis.
18:49Seven point, 1% had CNS relapse.
18:55So there there are many other
18:57findings from this study,
18:58but in interest of time,
19:00I'll briefly discuss their conclusions.
19:03What I found interesting from this study was
19:06that not only CNS IPI scoring is important,
19:09but they also found a significant
19:11CNS relapse rate in patients who
19:14had involvement of testis or liver.
19:16So that's something that we should keep
19:19in mind in our clinics, but overall,
19:22you know CNS relapse rates were similar,
19:25following prophylaxis,
19:25either intrathecal or high dose methotrexate.
19:28They are going to do comparisons of
19:30single versus dual route so intra fickle.
19:33In high doses in the future and also
19:36compare pro flexes and no pro flexes,
19:38which would I think be of interest
19:40to all of us?
19:41But overall outcomes for following
19:44CNS relapse remain poor without clear
19:46benefit from existing treatment options.
19:51Thank you and please use the chat
19:53window for questions while we go
19:55along with more presentations.
20:43Hi everyone. So I'll be presenting
20:47the update on primarily focusing
20:50on the Salem farmers. And.
20:55So just one at a couple of
20:58abstracts for indolent lymphoma.
21:00I have no relevant disclosures.
21:04So just starting with a brief overview.
21:09You know, dealing with the challenging
21:11field of T cell informers.
21:14You know there were a few studies
21:16that were presented that are off.
21:19Note that I'd like to highlight it in
21:22frontline peripheral T cell lymphoma.
21:24A couple of studies including the combination
21:27romidepsin job and as I said in chapter.
21:30Presented in relapsed refractory
21:33PTCL we had an update.
21:36On developer and relapsed refractory CDCR.
21:39There was a novel interleukin
21:41antagonist BNZ one,
21:43and then I will shift gears in
21:46touch on a couple of CLL studies.
21:50At the end.
21:52So talking about property selling
21:55former really the frontline treatment
21:58of this aggressive disease is a
22:00major area of clinical need and.
22:05You know, we most of us have been using
22:08CHOP or chop like regiments as the backbone
22:11chemotherapy backbone of frontline therapy.
22:14However, unfortunately,
22:15unlike diffuse large B cell lymphoma
22:18where our job has almost doubles,
22:20the CR rates that are seen with PTCL.
22:23So with PCL, which job we're looking
22:27at CR rates of just 35 to 40% in the
22:31setting of an aggressive lymphoma.
22:33This is really.
22:35A very challenging situation.
22:38Chip has been studied and shown to be
22:41of some limited success in certain in
22:44subtypes of patients in a subset of patients,
22:48specially those younger than 60 years of age.
22:52Much higher toxicity was seen in.
22:56Higher age group and those adjusted are.
23:01Suggested the bug is really considered
23:04for more aggressive subtypes like ATL and
23:08clinically aggressive presentations of PTCL.
23:11It's only recently that.
23:14No one study has changed the
23:16standard of care in CD.
23:1830 positive.
23:20TCL primarily in LCL Septics,
23:22where which where there was the most robust
23:25data for the combination of brentuximab,
23:28CHP from the Echelon two trial.
23:31But outside of this you know other studies
23:34that have tried to build on the chop
23:37backbone have not been very successful.
23:43So with this I'm going to present
23:46two frontline trials for PTCL,
23:48frontline treatment and
23:50so starting with Rd shop.
23:52So this was a phase three.
23:56A study conducted by the Lisa Group and
23:59again a frontline treatment of PTCL.
24:03It was presented by Doctor Vashi.
24:06So this study was based on the
24:09Phase 1B prior Phase 1B data.
24:13That showed. Basically a phase two
24:18dose of 12 milligram per meter squared
24:21was the one that was associated with,
24:24you know, but the best safety data
24:27given on day one and data for 21 day
24:31cycle with CHOP given on day one.
24:34This particular this is this
24:36prior study did have.
24:38Basically they give 8 cycles and a
24:41total of about 37 patients were studied.
24:45So in this present study presented
24:48by Doctor Bashi,
24:49this was a randomized controlled
24:51trial phase three data where
24:54the army was chop alone,
24:56and then I'm be had romidepsin,
24:58given in addition to chop again
25:01days 121 and eight at a dose of
25:0412 milligram per meter squared.
25:06The recommended phase two dose
25:09from the Phase 1B study.
25:12So in the study population,
25:15I do want to highlight that like
25:18many T cell lymphoma trials,
25:21it did include a very heterogeneous
25:24population of all aggressive
25:27histologies and then also looking at.
25:30One thing that is relevant really
25:33here is that patients undergoing
25:35autologous or allogeneic transplant
25:37planned as a consolidation
25:40were excluded from this study,
25:42which is really important to note because.
25:47A lot of people,
25:49even based on controversial data
25:51you consider autologous stem cell
25:53transplant for most patients who are
25:56eligible in first remission after
25:59after frontline treatment of PCL.
26:02The primary endpoint of this study
26:05was progression free survival and
26:07secondary endpoints included safety as
26:10well as additional efficacy endpoints.
26:13Again,
26:13baseline characteristics I want to
26:16highlight about half of the patients
26:19were of a ITL subtype and then,
26:22as expected,
26:23PCL and LCL where the other common subtypes.
26:28So here, unfortunately,
26:30like many other studies.
26:32But that have used chopped backbone.
26:35This was a this study did not
26:37meet its primary endpoint of
26:39improved progression free survival.
26:42The hazard ratio.
26:44For Rd shop versus R Chop Chop was
26:49appointed one with a P value of .096.
26:54And again,
26:55a subgroup analysis based on
26:57where this IPI factors.
27:00As well as histologies did not
27:02really show any significant
27:04subsets that were that achieve
27:06greater benefit from this regimen.
27:08But patients with AI TL did have.
27:11There was a trend too.
27:15Some benefit in this particular population,
27:18again looking at the overall
27:20and the complete response rates,
27:22the complete response rate was
27:2541% compared with 37%,
27:27which is consistent with
27:29historical data that we have from.
27:32Job. Again, without.
27:37Fighting any increase, additional efficacy.
27:39Rd job was more toxic.
27:42A substantial number of patients
27:44were not able to receive all
27:47doses of romidepsin as well as
27:50job and also significant number of
27:53patients are received.
27:55Had to undergo jobs reduction or
27:58interruption because of increased toxicity,
28:00which is primarily increased.
28:04Haematological toxicity so really,
28:07in summary for this study,
28:10Roach up increase toxicity without
28:13improving efficacy in frontline
28:15treatment of PTCL possible future
28:17directions really is based on
28:19whether CHOP is the right backbone.
28:22We do notes there.
28:24Drugs like romidepsin are more
28:26active in certain subtypes of
28:28PTCL like PTCL with T follicular
28:31helper, cell subtype and AI TL
28:34and so maybe's patient selection.
28:37And based on Histology and then there
28:41is another trial that is being.
28:44And that is yet to start accruing.
28:46But it's basically has been proposed
28:48by NCI where they're looking at the
28:51combination of Doxorubicin 5 as a as
28:53a sighted in oral and then romidepsin
28:56and develops it in T cell lymphoma.
29:00So those would be, you know,
29:02interesting things to look forward to.
29:04Our next study that was presented
29:07in Frontline PTCL was oral,
29:10is cited in CC-486 plus job.
29:13This was presented by
29:16Doctor Rowan from Kernel.
29:19So again, this particular study
29:21actually highlighted the point that
29:23an oral PCL with T follicular helper
29:26cell subtype is associated with.
29:30My hyperventilating mutations
29:32in the Ted in Ted 2D N MT3A and
29:36IDH 2 an in addition also roue
29:39mutations and this was the rational.
29:42These mutations are not only present
29:44in the two T follicular helper cell
29:48subtype AI TL but also some PTCL,
29:51PTCL nosc and so that was the
29:55rationale for using is cited in.
29:59As an epigenetic.
30:01Timer with chop.
30:04So this they proceeded straight to
30:06a phase two study because there was
30:09Phase one data for safety of this
30:11combination from B cell lymphoma.
30:13Uh, the they do.
30:15They do include all PTCL subsets.
30:18However they did prioritize enrollment
30:21of the T follicular helper cells
30:24upset and as you will see of the 20
30:28patients 17 where of TFH subset here?
30:31The primary endpoint was complete
30:34response rate and secondary endpoint
30:36was overall response rate and safety.
30:39They also looked at some genomic
30:42markers so this was an. Interesting.
30:47Study design and treatment regimen where
30:50initially CC 486 was given as a lead
30:54in from day minus 6 two day one for
30:57the first cycle and then subsequently
31:00from and subsequently four cycles.
31:04125 they received CC-486 on.
31:09Days 8 to 21 which basically
31:12so every so for cycle one.
31:15So this present this acted as priming
31:17phase for the next cycle of chemotherapy.
31:24So. After 21 patients that were enrolled,
31:2820 were evaluable for response
31:30and of these almost half of them.
31:33These patients actually did go on to
31:36receive autologous stem cell transplant
31:39or or one patient who received Alo.
31:42Here we see the overall CR overall
31:45response rate in CR rate in these
31:48patients in these 20 patients,
31:50and of all, all patients considering
31:53all patients as well as patients with
31:56PTCL default color helper cell subtype.
31:58It was seen that.
32:0188% CR rate was seen in TFs subtype
32:06compared with 75% all comers.
32:08Really, majority of the patients
32:11were of TFs subtype.
32:13Here are the results from the here.
32:16The survival curves,
32:17so the median follow up of 15 months.
32:22One year PFS was 66% for all patients
32:26and one year overall survival was 80%
32:30and the corresponding numbers for
32:32TFs subtype were almost 70% and 94%.
32:38This was a relatively well tolerated
32:41regimen with expected side effects of.
32:45Aside opinion, specially neutropenia,
32:47but other than the hematological toxicity,
32:51there were no additional
32:54significant unexpected side effects.
32:56This study also looked
32:58at mutational analysis,
32:59and it's worth mentioning that they
33:01found that tattoo was associated
33:03with a favorable prognosis in this
33:06cohort of patients and DMD MT3.
33:08Oh was associated with
33:09worse overall survival.
33:13So this was a surprisingly promising
33:15study and of this combination.
33:17Again, this is very early
33:20data of only 20 patients.
33:22So this is a, you know,
33:25a combination that is being tested further.
33:28One particular study that is worth
33:31highlighting is this alliance study,
33:33which is actually going to be rich is going
33:37to include patients with a C30 negative.
33:41PTCL non alc else Histology and it
33:44has it had three comparator arms one
33:48including CC 4861 including development
33:51and the third one is Chopper show up here
33:54with these combination they are using
33:57the backbone of Cho Absolute as well.
34:00It'll be worth looking at the.
34:05We can see. Of this these combinations.
34:11Next, I'd like to go onto a
34:14study with Dibella sub again,
34:16another promising new agent
34:17and T cell lymphoma.
34:19This was in relapsed refractory
34:21peripheral T cell lymphoma and
34:23this was updated data from the
34:26phase two Premier trial where they
34:28looking at those optimization and
34:30I'll go over that a little bit.
34:33This was presented by Doctor
34:35Pro from Northwest.
34:39So dualism is a dual appear
34:41three kindness Delta inhibitor.
34:42We know that is FDA approved
34:45in relapsed refractory,
34:46follicular lymphoma and CLL and
34:48the doors in these patients in
34:50these two diseases they approved
34:52doses 25 milligram vid when they
34:54tested this dosin T cell lymphoma.
34:56the Mac the MTD was 75 milligram
34:59PID vid and that was the dose
35:01tested in T cell lymphoma which
35:04showed an overall response rate
35:06of 50% in relapsed refractory,
35:08PTCL and 33% in cutaneous T cell.
35:11Former.
35:12So the reason that was the reason for
35:14designing this dose optimization study
35:16was to see whether these patients
35:19truly need 75 milligrams pob ID.
35:21Or are we overtreating them?
35:24So the study design.
35:26Again, there was a dose optimization
35:28phase followed by those expansion phase.
35:30It did include.
35:33The various,
35:35not subtypes that we discussed and.
35:40So develop the cohort one included patient
35:42develops if patients received develops.
35:45If 25 milligram B ID and cohort two.
35:48They received 75 milligram
35:50vid as the starting dose.
35:52The primary endpoint was overall
35:55response rate with these two doses
35:57and then the secondary endpoints
36:00again looked at additional
36:02safety and efficacy endpoints.
36:04So here we are looking at cohort one and
36:07go to each had 13 evaluable patients.
36:11So the overall response rates.
36:14Sorry so the overall response rates.
36:16Seen here with the 25 milligram.
36:20I was basically 35 to 40% by the
36:24investigator and the committee
36:26and compared with 75 it was
36:28a higher response rate.
36:30Overall response rate of 54 to 62% and
36:34then similar trends being seen in CR rates.
36:39When they looked at looking
36:41here at the waterfall plot,
36:43it was seen that all the early
36:45dropouts based of you to progression
36:47were in the 25 milligram dose cohort,
36:50and therefore they did in those expansion
36:54phase they decided to go on with.
36:57Using a adoes starting with a dose
37:00of 75 milligrams vid for two cycles.
37:03In those patients who had Disease Control,
37:06they would go on to receive
37:0925 milligrams pob ID.
37:12And now with this combination of doses,
37:16an overall response rate of.
37:2250% was seen with the CR rate of
37:2536% and so there there for this was
37:28the overall those expansion phase,
37:31including included 25 patients and
37:33this is a swimmer plot showing the
37:36duration of response for these patients.
37:42Again, in terms of side effects,
37:45there were no unexpected side effects,
37:48and the combination of those
37:50where you know those reduction
37:5225 milligram was associated with
37:55better tolerability overall.
37:59So again, this study highlights
38:01that develop is definitely an active
38:03agent in T cell lymphoma specific,
38:06especially in relapsed refractory PTCL.
38:08And that this going forward.
38:11This study provides data.
38:15For using this dual dose of 75 milligram,
38:19starting those with 25 milligram.
38:22Having a. Efficacy while balancing
38:26the toxicity of this single agent.
38:31So the last. See the last
38:36study in T cell lymphoma.
38:38Later, like to highlight is that and this
38:42is I'm going to go over this very briefly,
38:46but this looked at knew novel
38:49Interleukin antagonist.
38:50Starting the call going ambition of
38:53aisle to aisle 9 and I'll 15 by BNZ 1.
38:57And this was studied in a Phase 1
38:59two study and it was presented by
39:02Doctor Klarfeld from City of Hope.
39:05Today study different dose levels
39:08and it was those level two of two
39:12milligram per kilogram was decided as the.
39:16Phase two day for phase two dose based
39:19on the PK PD data there there was
39:22this drug was not associated with any
39:25major side effects and so therefore
39:28there was no MTD and based on the.
39:32So considering everything,
39:33including the efficacy data
39:34they discarded around to,
39:35go ahead with the dose of
39:382 milligram per kilogram.
39:40So this I want to highlight the fact
39:43this is was a really highly refractory
39:46population of CCL patients with medium
39:49file median 5 prior lines of therapy
39:53and without any major side effects of
39:56an overall response rate of 52% was seen.
40:00A subset of patients which is
40:03definitely makes this a very promising
40:05agent to go further in studies.
40:08They do did highlight that you know
40:12being targeted blocker of aisle
40:14to aisle 15 an aisle 9.
40:16It has a 3 prong.
40:19I can see where.
40:22Including direct anti tumor effect.
40:25Reduction of T regs and basically
40:28activation of anti tumor immune
40:30response and then also an anti
40:33inflammatory effect seen through
40:35I'll 15 blockade which is relevant
40:37for patients with PTCL who have a
40:40robust inflammatory reaction that
40:42leads to mobility in this disease.
40:47So with that,
40:48I'd like to quickly shipgirls too,
40:51and I will go through this very briefly.
40:54A couple of CLL abstracts,
40:56so the first one is locked, so 305.
40:59This is the next generation,
41:01highly selective non covalent BTK inhibitor
41:04in previous previously treated CLL SLL.
41:07And this was a Phase 1 two
41:10study presented by Doctor Matot.
41:12So lock the three or five.
41:15It's as previously mentioned,
41:17the highly selective non covalent BTK
41:20inhibitor in it inhibits both wild
41:22type as well as C481 mutated BTK.
41:25So when we see look at patients
41:27who have a BTK resistance,
41:29the most common cause of that is
41:32because of the mutations in BTK.
41:34And this drug does target
41:37that population of patients.
41:40But this was a these patients
41:43were heavily pretreated,
41:44including patients who had
41:46failed or discontinued,
41:48became a better for due to toxicity
41:51and also had this is a high risk
41:55population of patients with 17 P
41:58deletion and TP 53 mutation present
42:01present in a total of over 50% of patients.
42:07So the Phase one study,
42:09so the date data presented is
42:12from the Phase one study which
42:14included patients with CLL and SLL.
42:17And.
42:19Uh.
42:23This loss of three or five
42:26safety profile was unique,
42:27as in the the most common grade three side
42:32effect was actually fatigue and the typical.
42:36Side effects associated with other BTK
42:40innovators like atrial fibrillation.
42:42The side effects were not very
42:45prominent with locks or two or five.
42:48Since there was no DLT's,
42:49the maximum tolerated dose was not reached,
42:52and. Based on the PK data and the efficacy
42:57data dose of 200 milligrams was decided
43:00as the recommended phase two dose.
43:03Again, here it was in a heavily
43:05pretreated well population.
43:07Locks or three or five was found to be.
43:11Continue to have.
43:13Made up a very good efficacy in this.
43:17Beta in this patient population and looking
43:22at the overall response rate of 63%.
43:26So it was.
43:28It was a very.
43:30Good basically good response in
43:31this without a lot of toxicity
43:34in this patient population.
43:38So lots of three or five was
43:40active at all those levels,
43:42and typical became a bitter or
43:44related toxicities were not seen.
43:46These responses were independent,
43:48BTK mutation and even patients who
43:50had received BCL two inhibitor.
43:52When I took LAX as well as
43:54three kinase inhibitors,
43:55did respond to this drug.
43:57So there's a safety and
43:59efficacy signal in CLL.
44:01Yeliz will be passed participating in
44:03the phase two portion of this data.
44:06Of this study.
44:09Um? And then finally I just want to
44:12mention this particular study that
44:14was open at Yale in the past and
44:18that is umbrella civs and you've
44:20lytic seemab you two study which
44:23used a novel dual inhibitor π,
44:25three kinase and casein kind
44:27is money in a better and.
44:32The only issues with this study was
44:34that you know the comparator arm
44:37was a bit as a map chlorambucil,
44:39which is not really a very
44:41relevant in this day and age,
44:44at least for treatment naive patients.
44:46But this is being studied further
44:48in combination both in frontline
44:49and relapsed refractory setting.
44:54That's all I have.
45:16Tell everybody.
45:28Hello everybody, I'm going to go over the.
45:32Abstract relevant to heart killing
45:35form for the sake of time I'll
45:38try to be brief and uncover only
45:41heart killing form at this time.
45:44So since the introduction of Brentuximab and
45:47Odin and checkpoint inhibitors in general,
45:49the paradigm of treatment for this
45:52disease is changed substantially, and.
45:57And this agent,
45:58that now you been used earlier and
46:01earlier in the course of the disease.
46:03So I will review the knew,
46:05the updates and the new data relevant
46:08of the uses regarding the using of
46:10these agents in first line in the
46:12relapsed refractory setting and maintenance.
46:15Adding after transplant and
46:17in the elderly population.
46:19So let's start with that.
46:20The five year update of action on one,
46:23as we all know, this is a.
46:26A very large open label,
46:28multicenter randomized phase.
46:30Three study that was initially presented
46:33at three years ago at the Ash meeting
46:35with a 2 year follow up over 1300
46:39patients were randomized either to get
46:41brentuximab avd for six cycles or abvd,
46:44which is the standard treatment at
46:47city was performed after two cycles,
46:49but this was not a pet adapted approach.
46:52The primary endpoint of the
46:55study was a modified PFS.
46:58Which is which included time to progression
47:00that and not completely response
47:02and use of subsequent chemotherapy.
47:05This modified PFS was meant to capture
47:07all the events that reflected the failure
47:10of frontline treatment and patient
47:12and were followed up with the serial imaging.
47:15The first data set that was presented
47:19from this dialogue after a follow up
47:22Papa to essentially two years showed
47:24a benefit in using a plus abvd A plus.
47:27Abd compared to a DVD with an
47:31absolute in benefit of 5%,
47:33this modified progression free
47:35survival was 82 versus 77.
47:37This came at the cost of significant
47:41increase in side effects.
47:43Neutropenia 58% versus 45 from Europe.
47:46But there was a big big one
47:49with a 67% incidents.
47:51An informercial city was the one that
47:55was reduced due to the omission of the.
47:58Bleomycin.
47:59So why this is the five year
48:02five year update is important.
48:05We nearly all recurrences of Hodgkin
48:08lymphoma happen usually within five years,
48:10so we think that PFS of five year
48:13is a good surrogate for for cure
48:16an here the five year data we
48:19do see the PFS for the A plus.
48:22Avd is the red curve 82% of five
48:26years compared to 75% in the
48:28ABVD Ann and these disadvantage.
48:30And that was observed initially
48:32persisted overtime maybe depend.
48:34And this was how they threw in
48:37in patients achieving the path
48:39to negativity after two cycles.
48:41This hopper curb is 2 cars here compared
48:44to those that were at negative.
48:47So this was not a fat adapted approach.
48:50Again,
48:50the rates of if you remember the
48:53data from this work started.
48:55Yes,
48:55816 trial where patients had positive
48:57after two cycles received ended up
49:00receiving escalated Beacopp for six cycles.
49:02This PFS compared favorably to
49:04patients that received and much more
49:06aggressive course of treatment with a
49:08very high rate of secondary malignancies,
49:11and based on the profile and
49:13different risk characteristics.
49:14Applications are in the trial.
49:17Or the essentially all the group favored
49:20the use of brentuximab plus avd.
49:23So I think that was a highlighted
49:25and I think
49:26it's very important to note is
49:29that the peripheral neuropathy,
49:31which was one of the concern major concern
49:33when the initial results were released,
49:36has really improved or complete.
49:38Completely resolved in the vast majority of
49:42the patient and with an improvement that.
49:45Happened progressively over the
49:47course of the years and currently
49:49patients will receive one.
49:50Prefer neuropathy, have a really low
49:52grade of peripheral neuropathy, if any.
49:54Another thing that was noted in
49:56this five year update is that
49:58the rate of secondary malignancy.
50:00And the rate of successful
50:03pregnancies compared well to the ABVD.
50:05Um, so I think that with this five
50:08year update of the action and one,
50:10we have more compelling.
50:13Data now to support the use of this.
50:16Judgment and more widely in the
50:19in the upfront setting in hybrids
50:21in untreated stage, 4,
50:23three and four patients. Um,
50:25I just want to briefly briefly mention this.
50:28This trial,
50:29which was presented as a post office
50:31there is more that concept that was
50:34presented because this is an ongoing
50:37trial and we're part of it at Yale.
50:39He said as we just reviewed the
50:42addition of brentuximab window tint
50:45to avd improves PFS in advanced age,
50:48but still 15 to 20% patients are relapse,
50:51relapse or refractory and BV
50:54addition increases toxicity and
50:55require growth factors.
50:57So this is the this is the largest.
51:02North American Cooperative group
51:04trials in Advanced Hodgkin study that
51:08is being conducted in collaboration
51:11with Canada and even with the
51:14collaboration of the children.
51:16The theology.
51:19Patrick Oncology group for Hodgkin is
51:21a study that is planning to enroll
51:24987 patients and two randomized
51:27them either to nivolumab avd versus
51:29Brentuximab and Odin and Avd for six cycles.
51:33The patients are going to be satisfied
51:36based on the age Ipsy and intended
51:39use of radiation and the primary
51:41endpoint is progression free survival,
51:44but a lot of other data are planned
51:47to be gathered.
51:49And in particular,
51:50patient reported outcomes including fatigue,
51:52neuropathy, scoring and quality of life.
51:55So despite covid,
51:56it looks like the TARDIS.
51:58This trial is at the target of the
52:01expected accrual and the results
52:03of this trial are eagerly awaited.
52:05So let's move them to the salvage treatment.
52:08What's new in the salvage treatment?
52:11So usually provision that are relapsed
52:13refractory after the first line of
52:16treatment of the general approach is
52:18to proceed to salvage chemotherapy.
52:20Usually platinum based or genocide
52:22happen based with an expected
52:25response rate in the 5060% range with
52:27introduction of brentuximab concurrently
52:29or sequentially in the salvage regiment,
52:32we now expect responses in the
52:3460 and 70% range,
52:36but the use of a print aksamit now is
52:39getting limited by the fact that is
52:42used more widely in the first line
52:46and therefore alternative strategies
52:48that are being explored in this study.
52:51Specifically,
52:51is a face to study using bumper
52:54lizama in addition to our regular
52:57salvage treatment GD,
52:58which is one of the historically
53:01used salvage treatment as
53:02a second line for relapsed refractory
53:05article informal and eligibility
53:07dissipation that our love story factory.
53:10The first line of treatment.
53:12Primary endpoint is the PCR rate
53:15because that's the most important
53:17factor that we that we have to
53:20achieve after salvage treatment.
53:22With Adima to pursue to transplant.
53:25So patients received the regular GBD
53:28combination and they want and they ate
53:31with addition of populism on day one.
53:34After two cycles of patients
53:37but positive patient back,
53:38negative were allowed to
53:40pursue directly to transplant.
53:42Otherwise everybody received 4 cycle
53:45and then that was evaluated at the end
53:49of treatment before the transplant.
53:51So let's see what happened.
53:53There were 939 patients enrolled in this
53:55study, with a median age of 38 years.
53:58Importantly,
53:58most of the patients were advanced
54:00age of the initial diagnosis
54:02and the time of enrollment.
54:04When they relapsed,
54:05many patients had extranodal site,
54:061/3 of them extranodal sites
54:08of disease involvement,
54:09and the symptoms was present
54:11in 15% of the patient.
54:14Almost like 40% were refractory
54:16or either they relapsed in first
54:19year so very high risk patient
54:21population and the treatment they
54:23received up front was primarily ABVD,
54:26but some patients reserved receive the
54:28print axiom an and or Veeco approaches.
54:31So after the first 2 cycles
54:34of pembrolizumab T 92% of the
54:37patients were found to be in a CR,
54:40and that's unprecedented data
54:42for a salvage attachment.
54:44And after an additional 2 cycles and
54:47there was an additional CR rate,
54:49so the total see CR rate for this
54:52group of patients was 95 percent,
54:5595% proceeding to transplant and a
54:57good amount about a third of them
55:00preceded to maintenance with the
55:02print accent windowed in for a year.
55:05Based on the accurate trial study,
55:07an none of the patient with limited
55:10follow up that we have now for this
55:13study at progression of disease.
55:15After the transplant. So why this this?
55:18This regiment works so well.
55:20It even outperformed what checkpoint
55:22plus chemotherapy does in first line.
55:24Sony Vollmer Avd does not have the
55:27same efficacy and one of the reasons
55:30that the others are looking into
55:32is if there is anything specific in
55:35this may be the synergy between the
55:37chemotherapy agent that is unique to
55:39this regiment inside I mean with a
55:42checkpoint inhibitor in particular
55:43the ability of selectively eliminate.
55:46That my little derived suppressor cells,
55:48so these exciting results poised base
55:51for the next court on this study,
55:54were actually the aim is to treat
55:57everybody with Pembridge EBD for four cycles,
56:00and then skip the Trump's transplant
56:02altogether and have the patient instead.
56:05Being on maintenance with 13 cycles
56:07of pembrolizumab maintenance.
56:08So this is going to be very exciting to
56:13see what the outcome of this patient is.
56:17Moving forward,
56:18let's talk about consolidation after
56:20transplant. What's new in that?
56:21We know that patients at high risk
56:24of relapse after the transplant
56:25based on the characteristic primary
56:28refractory disease.
56:29As general involvement with symptoms
56:30of relapse order requiring more
56:32than one line of salvage treatment,
56:34not in CR, the time of transplant,
56:37they are higher risk of
56:39relapsing after transplant.
56:40So now there have been strategies
56:42that have been explored that
56:44to improve their PFS and.
56:46We all know about the if their trial
56:48where baby consolidation was was utilized
56:51after atleast himself transplant
56:53with an improvement of the PFS,
56:55although with a significant there
56:57was a 33% and drop off patients
57:00that could not complete the study
57:03due to neuropathy and another
57:05study that has been done used that
57:07embolism up in this setting.
57:09It was much smaller study only
57:11with 30 patient and patient
57:13population and better risk factors.
57:16So the apotheosis behind this study
57:18is to use the these two agents
57:21in combination Vivian Evil as
57:23consolidation and utilizing only
57:25eight cycles instead of the 16 cycles
57:28that was used in the fair trial,
57:31and again, patients that were enrolled,
57:3359 patients were enrolled in this
57:36trial and they were started on that.
57:39These are the combination between
57:41evil about them,
57:42between 30 and 6075 days after a transplant.
57:46And I just want to point out that there
57:49was a lot of patients that could not
57:53complete the eight cycles that were planned.
57:5759% could not complete the treatment
58:00plan and only 76% completed 8 cycles
58:03of either brentuximab or nivolumab.
58:06So the take home message from this,
58:09that is that the treatment the
58:12maintenance after transplant is a much.
58:15It is very difficult.
58:16Treatment too,
58:17for the patients to undergo as the side
58:21effects associated with the utilization
58:24of these agents in this setting.
58:27Is associated with an increased side effects,
58:30in particular immune related adverse
58:32event that we're seeing up to 27% of
58:36the patients enrolled in this study.
58:39But nevertheless,
58:39it's very encouraging that there is
58:42a 92% progression free survival in
58:45this high risk patients for relapse
58:48even despite their prior exposure
58:50either to BB and anti PD one.
58:53And since I want to leave sometimes
58:56for question.
58:57I'm just going to mention briefly
59:00that this study think the merit
59:02of this study has been literally
59:04to enroll older patients which
59:07are under representative in most
59:09of the Hodgkin lymphoma trial.
59:11They have less prognosis and unfortunately
59:14I mean it's not a randomized trial,
59:16so patients were received either BV
59:19in monotherapy or in combination with
59:21chemotherapy and just to be very,
59:24very quick.
59:25The take home messages that
59:27DV monotherapy has been with.
59:29Very, very active, but as shown,
59:31the employer in prior studies,
59:33the PFS,
59:34was not very long,
59:35whereas when we've is combined
59:37with chemotherapy,
59:38the risks are outside effects increases,
59:40but it is associated with
59:43that much longer PFS.
59:45The only thing that they want I
59:47like is that the brand tax amount
59:50window 10 plus bendamustine armor
59:52was closed due to an excess of
59:54toxicity is not a good treatment
59:56in this elderly population.
59:57And with this I left panel open for question.
01:00:06Thank you all for presenting.
01:00:08It was really quite comprehensive.
01:00:10We're going to go over our allotted
01:00:12hour and folks can stay in.
01:00:14Will have a little question answer period.
01:00:17While we're on the topic of Hodgkin,
01:00:19that was really nice.
01:00:21Presentation documents tomorrow.
01:00:22How do you interpret and
01:00:24how do you take together?
01:00:25You know the five year data
01:00:27on the TV
01:00:28and first line.
01:00:30Incredible salvage options
01:00:31for patients you know.
01:00:33How do you put that together when you
01:00:36have someone that has advanced stage
01:00:38first line has come before you are you?
01:00:41You know the five year data compelling
01:00:43you to give more BVD or you still doing
01:00:46adaptive kind of raffle approach?
01:00:50This is this is a very good question.
01:00:53Interesting isn't it? It's very I mean,
01:00:56one of the argument against intensifying
01:00:59Firstline treatment is that is so well
01:01:02tolerated and that we have so many,
01:01:04I mean salvage therapy works in our chicken.
01:01:08So in order to improve.
01:01:11A small percentage of the outcome
01:01:13of all the patients you end up
01:01:16like exposing a lot of patients
01:01:18to a more aggressive treatment.
01:01:20While you could have served salvage only
01:01:23to those that do not respond to a DVD.
01:01:27So, but I think that this this five
01:01:29year update I really like to see that
01:01:32the peripheral neuropathy was not
01:01:34was getting better progressively year
01:01:37after year and there were not major
01:01:40sequelae regarding that approach and.
01:01:42I really like the fact that there
01:01:44was no not not an increase of
01:01:47secondary malignancy or of. The.
01:01:52Any bad outcome on pregnancies,
01:01:54but what I really think is the value of
01:01:57this approach as compared to PET adopted
01:02:00one is that you don't need to adopt it.
01:02:04The PFS of patients that have a
01:02:06pet positive after 2 cycle is very
01:02:09good and is as good as the one that
01:02:12you get using escalated beacopp
01:02:14and especially population.
01:02:17That's
01:02:17a really nice summary and I have
01:02:20very similar feelings of that,
01:02:21so it's a complicated
01:02:23conversation that certainly
01:02:24patients should be presented both.
01:02:25Kind of adaptive Anet DVD
01:02:27and tailored to patient
01:02:29preferences and kind of a profile.
01:02:31Not surprisingly, there are a number of
01:02:33questions about CNS prophylaxis of Doctor
01:02:35Kothari can step
01:02:36up to the plate, but you know how?
01:02:39How do you interpret the
01:02:41two abstracts that were presented oral
01:02:43session? I know there was a lot of kind
01:02:46of discussion during that meeting.
01:02:48Has that informed how you
01:02:50approach patients that are
01:02:51high risk for sinas that
01:02:53relapse? I think both abstracts kind
01:02:55of confused us further. To be honest.
01:02:58I mean it's great set of data,
01:03:00especially the second set of data that I
01:03:03presented which is a multi institutional US.
01:03:06You know study where there are more
01:03:08than thousand patients so you know
01:03:10the the end was pretty good to have
01:03:13meaningful interpretation, but I think.
01:03:16Overall, I think my summary of,
01:03:19I think both both abstracts
01:03:21would be that we need better,
01:03:24stronger frontline regiments to
01:03:26eradicate the real high risk DCL from
01:03:30the get go because that eventually
01:03:33leads to a CNS relapse and that
01:03:36was shown through the Alberta,
01:03:38Canada study where patients who
01:03:41got intensive chemo immunotherapy.
01:03:43The trend was towards better
01:03:46CNS relapse rates.
01:03:48And I guess the same could be told
01:03:50even you know the fact that autologous
01:03:53stem cell transplant was helpful.
01:03:55So overall,
01:03:56I would say that this these abstracts
01:03:59don't change my practice of using
01:04:01high dose methotrexate with R
01:04:03CHOP or most likely into fecal
01:04:05methotrexate with those adjusted
01:04:07epoch in high risk blpi atients.
01:04:09What I would say I think,
01:04:11which was interesting to note,
01:04:13is the liver involvement
01:04:15and testicular involvement,
01:04:16which we traditionally don't.
01:04:18Think of it that way,
01:04:20although there are some
01:04:21scattered papers about it,
01:04:23I think this is just to highlight
01:04:25that you know liver and testicle
01:04:28involvement also portends
01:04:29higher CNS relapse rate.
01:04:32Thank
01:04:32you for that and then Doctor Safi.
01:04:35Really, I think lots of exciting
01:04:38early phase studies in T cell.
01:04:40But certainly I think we need kind of
01:04:43larger randomized prospective
01:04:44data and basically everyone with T cell
01:04:47lymphoma should be on
01:04:49protocol, right? If we're
01:04:51going to really
01:04:52start improving the
01:04:53outcomes, can you talk about
01:04:55some of the
01:04:56trials that we have open in T cell
01:04:59lymphoma either currently or in
01:05:02the future that? We hope to kind
01:05:04of increase our accruals for.
01:05:07Yes, absolutely. Actually we have.
01:05:09We do have a few exciting things
01:05:12coming down the Pike so we do use
01:05:15those adjusted epoch quite a bit for
01:05:18aggressive T cell lymphoma here at Yale.
01:05:22And so we have an IIT that is in the
01:05:25works which is which is funded and
01:05:28basically the protocol is being developed.
01:05:31And that's with those suggested
01:05:34epoch with mogamulizumab as frontline
01:05:36therapy in these patients and.
01:05:38So epoch does have overall, you know,
01:05:41looking at the chop response
01:05:43rates of like 3540% CR rates,
01:05:46epoch does tend to have a better
01:05:49overall response rate in CR rates in
01:05:52the 60% think you know 60% range.
01:05:55So the idea is really to try to get this.
01:06:00These patients and the deepest
01:06:02remission that you can and you know
01:06:06then then take them to transplants and.
01:06:09It's really an excited study.
01:06:11It is a phase two single arm study,
01:06:15but I think it's a novel combination
01:06:18that we're excited about.
01:06:20As far as the and one additional study
01:06:23would be in CD 30 positive patients
01:06:27looking at the combination of rituximab
01:06:30with pembrolizumab and that's kind
01:06:32of an idea that I wrote at Vanderbilt
01:06:36and Vanderbilt that we're hoping to open.
01:06:40In the coming months as well.
01:06:42As far as the present studies are concerned,
01:06:45the ones that we are still enrolling on,
01:06:49we have a couple of oral agents,
01:06:51including the DIETY study,
01:06:53which is basically an IDH one,
01:06:55IDH, two inhibitor.
01:06:57And it has to be.
01:06:59It has, you know,
01:07:00single agent activity in relapsed
01:07:02refractory T cell lymphoma,
01:07:04and definitely something that
01:07:05we've seen responses with,
01:07:07and sometimes it's just the right
01:07:09treatment to try to get these
01:07:11patients in remission,
01:07:12take take them to transplant.
01:07:16Thank you so much and this was great.
01:07:19Amazing talks and thanks God
01:07:21for this the moderation.
01:07:22The questions as you heard a
01:07:24lot of exciting developments
01:07:26going on in the informal work.
01:07:28We have a lot of actually
01:07:30active clinical trials,
01:07:31so feel free to reach out to any
01:07:33further Informa experts or any
01:07:35questions about your patience or
01:07:37any referrals for clinical trials.
01:07:39Reminder that a recording of this
01:07:41session will be available next
01:07:43week and along with the slides and
01:07:45should be an enduring material.
01:07:47For your future reference,
01:07:48next week will have the by Lloyd
01:07:50updates and thank you so much
01:07:52everyone and have a great weekend.
01:07:53Thank you.