Yale ASH 2022 Highlights: Lymphoma

March 03, 2023

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Hosted by: Dr. Scott Huntington

Presentations from: Drs. Francesca Montanari, Shalin Kothari, and Tarsheen Sethi

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00:00Thanks for joining for the fourth
00:02session of the weekly Yale Cancer
00:05Center 2023 post Ash CME review.
00:08Today we'll be going over
00:10lymphoma and I'm Scott Huntington,
00:12lymphoma specialist here and I had
00:14the distinct pleasure of introducing
00:15our three presenters today.
00:17Our first presenter is Francesca Montanari,
00:20who will be presenting an indolent lymphomas.
00:23Dr. Shalon Cathari will go next
00:25and present aggressive B cell
00:27lymphomas and then doctor Tarsin
00:29Sethi will be presenting T cell.
00:31Performance and harsh gonna follow
00:33the rest of the lymphoma group is
00:35pictured here including Doctor Sufi
00:37and Doctor Foss who see lymphoma
00:39but also do cellular therapeutics.
00:41And then Doctor Seropian is really
00:44fixed in terms of his clinical
00:47practice on cellular therapeutics.
00:48But this is the broad group here
00:51including Doctor Montanari who
00:53sees patients at Smilow Greenwich.
00:56So I think we'll move to the
00:58remainder of the presentation.
01:00If there's additional
01:01questions that you have,
01:02please use the chat feature or
01:03question and answer and we hope to
01:05have about 10 minute discussion
01:06at the end of this presentation.
01:18Doctor Montanari mute. Those things happen.
01:23Sorry about that.
01:25I'll start sharing with you my selection
01:27of abstract of indolent lymphomas and I
01:30have no conflict of interest to disclose.
01:33This is my abstract selection.
01:34We'll start, we'll space from first line,
01:37second line by specific antibodies,
01:40single agent and in combination
01:42and ultimately we'll review a
01:45new model for prognostication.
01:48So the first abstract I've selected
01:50is the long term follow-up of an
01:52international randomized phase three
01:54study of rituximab versus watching weight
01:57approach in patient with asymptomatic
02:00low tumor burden follicular lymphoma.
02:02Our current approach in these patients
02:05population is watch and wait based
02:07primarily on data on the Prairie
02:09taxicab area that teach didn't show
02:11any benefit in early treatment.
02:13This study earlier analysis led
02:15to the approval of rituximab.
02:18Connection.
02:18In this patient population in the
02:20UK and then here is a presented the
02:24long-term follow-up analysis with
02:26a median follow-up of 12.6 years.
02:29Umm, here's the schema of the uh trial.
02:33Uh patients have 8018 year old,
02:36years older within three months of the
02:39diagnosis with the Grade 138 follicular
02:41lymphoma and early stage from two to
02:44four with no organ dysfunction and no
02:46symptoms and low burden of disease.
02:49And we'll randomize the to receive it.
02:51I watch and wait approach
02:53rituximab induction,
02:54which consisted in rituximab weekly times
02:57four or tumor induction plus maintenance.
03:00For up to two years and the follow-up
03:03they were monitored with the
03:06serial imaging primary endpoint,
03:08time to initiation of a new
03:10treatment and quality of life.
03:13India is a update with a median
03:16follow-up duration of 12.7 years.
03:18The medium time to initiation of
03:21first line treatment was 22.7 years
03:23for patients in the watch and wait
03:25approach compared to almost 10 years
03:27in patients with rituximab induction
03:29and not reach the poor patients with
03:31rituximab induction plus maintenance.
03:35Time from randomization to second
03:38treatment was a similarly no
03:41difference between the three arms.
03:46In terms of overall survival,
03:47there was no difference in the overall
03:50survival between the true group,
03:51the three groups that median overall survival
03:53was not reached in the watch and wait,
03:56and the taxman maintenance group and was
03:59a 17.4 years in the rituximab induction.
04:0420% of the 20% of patients that died on
04:07average on each arm and 10% of the deaths
04:11were attributed to the lymphoma. Um.
04:13In terms of high grade transformation
04:15and time to 2nd malignancy,
04:17again no difference between the three
04:20groups with about 20% events of high
04:24grade transformation in each arm and 20%
04:27of secondary malignancy in each group.
04:31So the other concludes the conclusions
04:33that are are that earlier taxing up
04:35treatment should be considered a standard
04:37option in patient with low turnover
04:40than asymptomatic follicular lymphoma.
04:41Given the significant advantage in time to
04:44new treatment and no detrimental effect
04:46on high grade transformation rates,
04:48secondary primary malignancy and
04:51previously reported improvement
04:53in quality of life measures,
04:56is this practice changing?
04:58I think this is a this is a very valuable.
05:02Data set that will provide us a little bit
05:04more flexibility to better individualized
05:07treatment based on patients preferences.
05:09I find a very,
05:11very reassuring that 1/4 of patients in
05:14the watch and weight arm at 12.7 years of
05:17follow-up never required any treatment.
05:19So I think that this trial also
05:21reinforces our approach of watching
05:23with strategy in these patients,
05:25but it's also good to know that it's
05:28not detrimental to start rituximab in
05:30those patients who for life preference.
05:32Decide to be more uncontrolled
05:34of their disease.
05:352nd abstract I've selected is A5
05:37year overall five year results and
05:40overall survival update from the phase
05:42three augment trial Lenalidomide plus
05:45rituximab versus rituximab plus placebo
05:47in patients with relapsed refractory
05:50indolent and Hodgkin lymphoma.
05:52As we all know the AUGMENT study the
05:55R square the demonstrated superior
05:58efficacy compared to rituximab placebo
06:00in patients with relapsed refractory
06:02and non Hodgkin's lymphoma leading
06:04to the approval of.
06:05These combination in previously
06:07treated follicular and marginal zone
06:09lymphoma when the initial analysis
06:11was published in 2019.
06:13Just reminding the schema of the
06:18trial patient that with the follicular
06:20lymphoma grade 123A or marginal zone
06:23lymphoma that received one prior line
06:25of systemic treatment and documented
06:28relapse refractory disease but
06:30not refractory to rituximab where
06:33stratified and randomized to learn.
06:35Metaxa amab as we as it is currently
06:38approved for with the Lenalidomide
06:40for one full year of treatment and
06:43rituximab given during the first five cycles,
06:46it's only for the 1st 5 cycles and the
06:49rituximab placebo was given similarly
06:52primary endpoint being PFS secondary
06:56endpoints including overall survival.
06:59And we,
07:01uh,
07:02with the additional follow-up
07:04provided with this update at a median
07:07follow-up of 65.7 months,
07:09median PFS continued to favor the
07:13R Square group 27.6 months versus
07:1614.3 months in year placebo group
07:19time to the next lymphoma treatment,
07:22which is a more subjective kind
07:25of measure because time
07:26to initiation in 320 lymphoma.
07:29Is not as a standardized um was continued
07:33to favor the R square 73.1 months
07:37versus 31.8 months for our placebo.
07:39And with fewer patients in the R
07:42square arm receiving more than one
07:45subsequent lines of treatment.
07:47And I think this was the most important,
07:49the most relevant data that with
07:52the overall survival analysis with
07:55this median follow-up extension
07:57and the two curves have remained.
07:59Continues to separate.
08:01Although the median overall survival
08:03was not reached in either arm,
08:05there was an improvement in the overall
08:07survival and the R square compared to
08:10the R placebo hazard ratio was 0.59 and
08:13P significantly statistically significant.
08:15Um.
08:17And there were no new treatment
08:20emergent is reported in this update.
08:23This work come came from
08:24the original analysis.
08:25So not surprisingly there were more
08:28toxicity on the R square group compared
08:31to the R placebo and especially with
08:34the most common being neutropenia.
08:36But in the long term,
08:37there was no signal that was
08:40worrisome for an increase in the risk
08:43of secondary primary malignancies
08:45due to Lenalidomide exposure.
08:48Or histologic transformation.
08:49So I think that these updated
08:51result further support the use of
08:54this combination in the relapse
08:55refractory setting.
08:59Moving forward, I'd like to review data on
09:03the city 20 CD 3 by specific antibodies.
09:07This was a very big and very popular
09:10topic attitude this year ASH meeting
09:12this antibody as we all know binds
09:15CD20 and malignant cell CD3 on T cell
09:18eliciting T cell mediated toxicity.
09:21We will review here the efficacy and safety
09:24data on Mozilla on other next AMAB and.
09:28The combination of equipment
09:30that with our square,
09:32I just want to highlight here that most
09:34mob after the this data were presented at
09:37the ASH meeting very earlier this year.
09:40I received accelerated approval for
09:42follicular lymphoma would receive at
09:45least two prior lines of treatment
09:47including an anti CD20 antibody and
09:51an alkylating agent or the next Amada.
09:54Also very promising results we're
09:55going to review as being granted
09:57fast track designation by the FDA.
09:59Or fully comic drama.
10:01So here the update on uh,
10:04the people that were phase two
10:07study on monotherapy in patients
10:09with relapsed refractory lymphoma.
10:12Key inclusion criteria included
10:13patients with follicular lymphoma
10:15grade one to three a with a good
10:17performance status with more than
10:18two prior lines of treatment.
10:20The by specific antibody was given
10:23intravenously with a step up
10:26dosing in cycle one that is usually
10:29a strategy to mitigate.
10:31The risk of CRS that that is unique to
10:34this group of drugs and then subsequent
10:37to the step up dosing was a given day
10:42one of every cycle 60 milligrams with
10:45cycle two down to 30 with cycle 3
10:47on it was a fixed duration treatment.
10:49People achieving patients achieving
10:52CR after 8 cycles stopped treatment
10:55and we're allowed to be retreated
10:58should the recurrence patient
10:59achieving a stable disease.
11:02Was a partial remission continued
11:03on the treatment for 17 cycles.
11:05There were no mandatory hospitalization
11:08and the study made its primary
11:11endpoint of efficacy at the prior
11:13published initial analysis with a
11:16rate of 60% in patients that compared
11:20to 14% of historical control.
11:22And here it was provided an updated efficacy
11:26and safety analysis with a longer follow-up,
11:2910 months longer than the original analysis.
11:33Baseline characteristics I
11:34just want to highlight here,
11:35these were very,
11:36very heavily pretreated patients
11:38and patients up to the age of 90
11:40were included in the study and
11:42there were a lot of significant
11:44proportion of what we call PD-24,
11:46which are very, very high risk patient
11:49that usually have a worse outcome.
11:52Um,
11:53these analysis,
11:54there was no difference in the
11:57reported efficacy compared to the prior
12:00analysis with an overall response rate
12:02of almost 80% and a CR rate of 60%.
12:05Very quick time to 1st respond 1.4
12:08months and three months for the time
12:10to the CR I think was what is more
12:13meaningful about this update is
12:15that the duration of these responses
12:18and the benefit that appeared to
12:20be very impressive especially
12:21when compared to the benefit.
12:23Achieved with the prior line of treatment
12:25before Mozilla Tusm having these
12:27patient as we see here the blue line
12:30is most inotuzumab prior to your 20s
12:32in red median duration of complete
12:35response not reached for monotheism
12:3715 months for prior treatment and
12:41PFS similarly favoring like was
12:44was 24 months compared to 12 months
12:47for a prior line of treatment.
12:49And I think this is very important in
12:51the because breaks as sort of the.
12:53Vicious cycle in patients with particular
12:55lymphoma with subsequent lines of
12:58treatment usually and the duration
12:59of response is half of the prior one.
13:02In terms of safety profile,
13:04there was not an update on the ages
13:08reported in the original analysis
13:10and most of the adverse event not
13:12related to CRS where Grade 3 and grade
13:15four were essentially neutropenia
13:17and hypophosphatemia which seemed
13:19to be appear to be manageable.
13:21And also in terms of CRS,
13:24most of the CRS were predictable
13:26after the first dose and after the
13:28first full dose of the antibody,
13:30mostly grade one and grade.
13:32That was on a grade three and a grade
13:34four was in a patient that apparently
13:35had a leukemic form of follicular
13:37lymphoma with a very high white count.
13:39So had a really high risk features.
13:41And again this is I think practice
13:44changing after the FDA approved this
13:46drug in the third line setting,
13:48we have now a new option and it's
13:50very exciting and it's probably
13:52going to be in direct competition
13:54with car T cell in this space.
13:56I just want to highlight here a
13:59poster presentation that has.
14:02If in time happens when a drug shows
14:04such an amazing activity in patients
14:06that are heavily pretreated and
14:08in subsequent line of treatment,
14:10it is attested earlier in the course
14:13of the treatment and in combination
14:16with the approved treatment.
14:18And we have currently opened here
14:20at Yale under the lead of Doctor
14:23Huntington clinical trial here's in
14:26combination in collaboration with
14:27Brown University.
14:28This is a map with the land.
14:32Augmentation as first line therapy
14:34for follicular and marginal zone
14:36lymphoma in these clinical trial
14:38patients with untreated follicular
14:39and marginal zone lymphoma in need of
14:41treatment will be treated with Mozilla.
14:44As we reviewed previously.
14:47The same schedule is going to be
14:50given though subcutaneously after
14:51four cycle patients in CR will
14:54continue for a total of eight
14:56cycle patient not achieving CR.
14:58So with the partial response of
15:00stable disease will go on receiving.
15:02Augmentation with Lenalidomide 4 to
15:04complete its cycle and then there is
15:07provision for an extended documentation
15:09if no CR is achieved after cycle 8.
15:11Primary endpoints of the studies
15:13are overall response rate,
15:15CR rate and PFS and there are
15:17correlative studies looking
15:18at the tumor microenvironment,
15:20CD, circulating DNA and MRT.
15:26Moving forward,
15:27the other very promising by specific
15:29antibody that was presented at the
15:31ASH meeting in follicular lymphoma
15:33is other next amab and be very quick
15:35here because it's essentially the
15:37data are similar to the one that
15:40we have reviewed with most about
15:42though the follow-up was much shorter
15:45and it is given with a step up dosing
15:48that was changed in the course of the
15:51study to further mitigate the risk of
15:54a Sears and so it was a little bit.
15:57Or day one and day two they get
16:0091516 of cycle 1 escalated to the
16:03full dose Hollywood cycle two.
16:05And the way that these by specific
16:07antibody was given as a sort of
16:10maintenance continuous treatment
16:11every two weeks of again here we
16:14see similar response rate than we
16:16have seen with most of a very high
16:20overall response rate over 80% and the
16:23complete response rate 75% medium.
16:26Uh opportunity to follow up has
16:29been uh 2022.4 months.
16:30And in terms of safety profile,
16:33again similar to mob neutropenia
16:37was a big adverse event.
16:39Besides the CRS and CRS risk were
16:42mostly grade one and Grade 2,
16:45especially after the optimization
16:47of the step up regimen,
16:49Grade 3 became much less frequent
16:51and just to remind what is a
16:54big deal at Grade 3 CRS.
16:56Is that with the demand high grade
16:59oxygen and vasopressor support?
17:03Finally, I'd like to review this study,
17:06the subcutaneous combination of
17:08eculizumab with rituximab and
17:10Lenalidomide in patients with relapsed
17:12or refractory follicular lymphoma.
17:14So by specific antibody in combination
17:17with an approved chemo immunotherapy
17:19and these were patient with follicular
17:23lymphoma relapse refractory need
17:25for treatment and there were.
17:27Included higher risk patient epically
17:31was given subcutaneously and for.
17:36And was given in combination with
17:39rituximab and lend a little while
17:41following the AUGMENT schema.
17:43Treatment lasted 2 years.
17:45Primary objective was in safety
17:48and antitumor activity.
17:51Treatment emergent adverse event
17:53as expected based on the R square
17:56toxicity profile and I think the study
17:59was impacted by the fact that it was
18:02conducting during the COVID-19 pandemic.
18:04With many patients contracting the CD 19,
18:07COVID-19 in less CSS,
18:09the event very minimal,
18:12very encouraging these results and
18:15mostly grade one and grade two no
18:18grade three years was recorded and
18:21overall response rate 95% with a
18:25complete metabolic response of 80%.
18:27So based on these very exciting
18:30results there is currently a
18:32phase three trial of subcutaneous.
18:34Create the mapping combination with
18:36our square uh versus uh R square among
18:39patients with relapsed refractory
18:41follicular lymphoma that is ongoing.
18:43I'd like to close my selection of
18:46abstract with uh these abstract
18:49on prognostication.
18:50This is a very important and
18:53area of clinical and met need for
18:56follicular lymphoma.
18:57We know the patients of particular
18:59lymphoma is very terrigenous with the
19:02patient doing well on the watch and
19:04wait approach for more than 12 years
19:06and patients instead relapsing with
19:08their disease within 24 months from
19:10initiation of a chemo immunotherapy
19:12and those are really the patients.
19:14That we really need to do more
19:20research and develop new treatment
19:23paradigm for because these are the
19:26patients that have the more challenging
19:29prognosis so in the this study.
19:32And it is presented at new prognostic
19:36model called Flippy 24 and this model
19:39was specifically developed to predict
19:41the risk of disease progression
19:43within 24 months from starting the
19:46first line of chemo immunotherapy.
19:48So we currently we have no current
19:51tool to identify these patients and
19:53having the ability of identifying these
19:56POD 24 patients earlier will help
19:59direct clinical trials and novel therapy.
20:01So these are flip 24 model uses 5 lineal
20:06variable age LDH hemoglobin WBC and
20:09beta 2 microglobulin which are very easily.
20:13Which are common variables that we have
20:15available for all of our patients and
20:18it's based on these five linear variables.
20:20It divides patient risks.
20:22Patients in five risk group,
20:25the low Risk group has less than
20:2710% chances of developing a POD 20
20:30to to progressive within 24 months
20:33from the initial treatment versus
20:35the very high risk has a very high,
20:37more than 40% chance of progressing
20:41and therefore I think that.
20:44This model would provide a good
20:46platform for future models and
20:49incorporating maybe other information.
20:51Tumor total metabolic tumor volume
20:53seems to be an emerging important
20:57independent predictors,
20:58predictors for response especially in Carti.
21:01We don't have a lot of data about
21:03that in by specific antibodies so far,
21:05but I think this was a good start.
21:10So in summary, we have reviewed the
21:13data that showed that the rituximab
21:15induction plus of maintenance plus
21:16or minus maintenance appears to
21:18be non inferior non detrimental
21:19alternative to watch and wait for
21:21selected patients with asymptomatic
21:23low tumor burden for liquor lymphoma.
21:255 year follow-up of Lenalidomide of
21:28Ataxia map continues to show PFS and
21:31an overall survival benefit compared
21:33to placebo with rituximab CD20CD3
21:35bispecific antibody demonstrated durable
21:37efficacy with manageable toxicity and.
21:40High risk patients with follicular
21:42lymphoma and was INOTUZUMAB has now
21:44received the accelerated FDA approval
21:45in patients with follicular lymphoma.
21:47In the third line setting.
21:49There are ongoing clinical trials
21:51that are evaluating by specific
21:53earlier in the lines of treatment
21:55and in combination with approved
21:57treatments and the identification
21:58of diagnosis of PDD 24 patients is a
22:02very important clinical unmet need.
22:03This new flip 24 model proposed
22:06by Mayo Clinic and emerging data
22:08on a total metabolic tumor.
22:11Burden and hopefully will help
22:14us prognosticate better these
22:16subset of patients.
22:17And with this,
22:19I'm gonna stop sharing my presentation.
22:23I'm going to let Doctor Shalin
22:27Kothari take over and discuss
22:30Mandelson and aggressive lymphomas
22:31and I'm happy to take any question
22:33at the end of the presentation.
22:43But. One second. OK, can you see my screen?
22:51We see your PowerPoint. You want perfect?
22:56Slide show if you want to go.
23:05Perfect.
23:07So I'm going to focus more mainly
23:09on large B cell lymphomas,
23:11mainly aggressive B cell lymphomas
23:13and mental cell lymphoma have no
23:16relevant conflicts of interest to
23:18disclose for this presentation.
23:21The first abstract I chose was a
23:24biomarker driven treatment strategy
23:25in high risk large B cell lymphoma.
23:28The final results of a Nordic phase
23:31two study they this study included
23:34patients from 18 to 65 years of age.
23:38Histologically confirmed CD 20
23:40positive DLBCL, including Hygrid B,
23:43cell lymphomas and follicular 3B.
23:46They had to have at least stage two where
23:48the age adjusted IPS score of two to three.
23:51Uh with more than one external site
23:54of disease testicular lymphoma and
23:56paranasal sinus and orbital lymphoma
23:58with the destruction of the bone.
24:01And these are the clinical
24:03characteristics which are not
24:04too relevant to our discussion,
24:07but to kind of point out major pointers
24:10here that there are significant
24:12portion of patients with DLBCL Nos.
24:15With double hit and triple hit lymphomas
24:17and high risk biological characteristics.
24:24The way this study was run was
24:27patients were allowed to get some
24:29pre phase therapy if required.
24:31They received 2 cycles of our
24:32chop followed by interim staging
24:34and they were stratified based on
24:36these biological risk factors.
24:38So if they had one of these risk
24:40factors positive then they were
24:43escalated to receive those adjusted
24:45epoch for four cycles followed by
24:47rituximab with high dose Ara C
24:50with final staging via a PET scan
24:52if there are biological factors.
24:54Are negative then instead of infusional
24:58strategy R2 app was given for four
25:01cycles and then they were off study.
25:05And the biological risk factors
25:07included are all clinically relevant,
25:08something that we always do in the clinic.
25:11So single Mic rearrangement,
25:13DHL double hit lymphoma or
25:16double expressor lymphoma,
25:19P53 positive by IHC or P53 deletion and CD5
25:24positivity and these are the PFS curves.
25:28So you can see that with this escalated
25:32strategy they were able to improve
25:35overall outcomes for biologically high
25:38risk large B cell lymphomas with PFS
25:42close to statistically insignificant
25:45biologically low risk disease.
25:48And if I were to,
25:50you know further stratify the
25:53high grade B cell lymphoma with
25:55double hit disease had a similar.
25:59DFS as biologically as some some
26:02patients with no double hit lymphoma.
26:06Where this strategy did not fare well
26:08is in patients with TP53 deletion
26:11where I think we still need to figure
26:14out better strategies and a normal
26:17novel strategies such as car T cell
26:20therapy and and bispecific antibodies
26:22might be more helpful in upfront
26:25strategies for for TP53 aberrated disease.
26:28Umm.
26:28The next study I wanted to focus
26:31on is abstract 735 five year old
26:34five year survival results from
26:37remodel trial which showed improved
26:40outcomes in DLBCL molecular subgroups
26:42from addition of MIB to archtop
26:45immuno chemoimmunotherapy.
26:48The study aim was based off.
26:51Some preliminary preclinical data
26:52that Bortezomib and in general
26:54proteasome inhibitors would have.
26:58If there is a signal in the
27:01preclinical world for the better
27:04outcomes with ABC DLBCL models,
27:06so the study design was patients
27:10who had advanced stage DLBCL,
27:12they were consented,
27:13eventually received first cycle of our job.
27:16While they were receiving that cycle,
27:18biopsy was sent for molecular
27:20profiling and mainly it was genus
27:24expression profiling platform.
27:26And then there were stratified
27:28based on molecular phenotype and
27:30IPI score and they were randomized
27:32to receive five more cycles of
27:35our job with Bortezomib or five
27:37cycles of our chop alone.
27:39Important to point out here that
27:41the the the there was an amendment
27:44where the dose of Bortezomib was
27:46increased from 1.3 to 1.6.
27:48In the middle of the trial there
27:50was interim analysis which showed
27:52that the benefit was mainly in the
27:55ABC's phenotype and hence they
27:57adjusted some of their parameters,
28:00analysis parameters based on that.
28:04And this is the distribution of patients.
28:07It was nicely balanced between
28:10the two groups and between
28:12the two treatment modalities.
28:14And these are the results.
28:16So you can see that there's a clear
28:20difference and statistically significant
28:23PFS and OS benefit in ABC DLBCL in
28:28contrast to GCB DLBCL molecular high.
28:32High risk group or as a subgroup
28:35that they had defined.
28:38It was a predefined subgroup based
28:41on multiple different parameters
28:43put together as part of the gene
28:46expression profiling and that
28:48group also showed statistically
28:50significant difference in PFS with
28:52addition of Bortezomib to our job.
28:57The next study I I wanted to focus on
29:00is a prognostic index called Lab Pi in
29:05DLBCL validation study on behalf of the
29:09Spanish Lymphoma Cooperative group.
29:11So here I'm showing all these
29:15different prognostic variables that
29:17we sometimes use in the clinic.
29:20But mainly we rely, as we all know,
29:22in on our IPI&amp;RIPI.
29:26These authors designed a prognostic
29:29parameters which are much easier to do,
29:32cheaper to do and more easily
29:36available in developing countries.
29:39So the the the three parameters
29:43included high LDH anemia of less
29:45than 12 in men and 13.5 in females,
29:49high beta 2 microglobulin for
29:52and two points for high beta,
29:55remarkably more than 4 milligram.
29:57Or leader?
29:59Umm.
30:00So what they they authors go
30:03to an extensive length to show
30:06that this this particular index
30:09is predictive and prognostic.
30:12But I'm just showing the EFS
30:14and OS curves here,
30:15and they nicely correlate with the
30:18IPI score that we use commonly.
30:22Based on stratification based on
30:24the points of 01 to 2-3 and four,
30:27which corresponds to lower,
30:29lower, intermediate, high,
30:31intermediate and high IPI scores.
30:36The next abstract that I wanted to focus
30:39on is a polatuzumab vedotin combined
30:42with rice or our ice as second line
30:47therapy in relapsed refractory DLBCL.
30:50So as we know the current standard
30:51of care in relapsed refractory
30:53DLBCL relapsing more than one year,
30:55so not primary refractory after first line
30:58treatment is salvage treatment followed
31:00by autologous stem cell transplantation.
31:03So the hypothesis for this study.
31:05Was that polatuzumab vedotin combined
31:08with rice salvage chemotherapy
31:09as first salvage treatment would
31:12be safe and effective bridge to
31:14autologous stem cell transplant.
31:16The inclusion criteria was pretty broad.
31:21Adult patients with performance status
31:23of zero to two with relapse refractory
31:26disease after first line therapy that
31:29must have included anthracycline.
31:31It also included transformed DLBCL,
31:35PMBCL and high grade B cell lymphomas.
31:39And they of course have to be
31:41transplant eligible and this is
31:44the patient characteristic table.
31:46And it's important to note that there
31:49were equal distribution between primary
31:51refractory disease and relapse disease.
31:54Most patients were at stage four or
31:58three at advanced stage at at relapse
32:02and 78% of these patients had received
32:05our chop and 22% had received our epoch.
32:09And 17% of patients were double
32:12hit lymphoma and 34% were double
32:14expressor lymphoma.
32:15And something important to note out
32:18is that transformed lymphomas was a
32:20pretty significant representation
32:22with almost 30% of patients.
32:25The way this salvage therapy was given
32:28was at those level one basically it's it
32:31was rice therapy in addition to polatuzumab,
32:34the door to and given on day one
32:37at 1.8 milligram per kilogram.
32:39And then once patients had received
32:41autologous stem cell transplantation
32:43after two to three cycles of polar ice,
32:46they would be eligible for polatuzumab
32:49consolidation of three to four cycles
32:52given every 21 days for a total of.
32:546 cycles.
32:59And these are the results.
33:01So you can see that a total of 441 patients
33:07were evaluated and 22 patients were
33:11able to get stem cell transplantation.
33:15So the authors did note that this is
33:18definitely a low percentage and there is
33:21possibly a signal that pulled out in May
33:24potentially cause problems with stem cell.
33:28Mobilization,
33:28but that needs to be studied further.
33:30But what is important to note here
33:33is the PFS and OS curves which are
33:37very encouraging in otherwise a very
33:39heavily pretreated amid other more
33:42biologically high risk patient subgroup.
33:45So here I show primary refractory
33:49patients and relapsed disease.
33:51So clearly polarized regimen is
33:53not an effective second line
33:56therapy for somebody with.
33:58Primary refractory disease,
33:59but for relapsed disease the PFS
34:03curves look very encouraging and
34:05this is the oral survival curve with.
34:08You know the time to median
34:10follow-up is still pretty low.
34:11So we need to look at this data more with
34:14more mature follow-up in upcoming years.
34:16But the overall survival curves look
34:19very encouraging in spite of many
34:21patients not receiving stem cell
34:23transplantation after polarize.
34:27The next abstract I wanted to focus on
34:30is Tafa Len in relapse refractory large
34:33B cell lymphoma real-world outcomes
34:35in a multicenter retrospective study.
34:38And this is in contrast to the ALMINE trial.
34:41And the authors go ahead and extensive
34:44length to to compare the L mine
34:47eligibility criteria and how Tafflin
34:49is currently being used in the clinic.
34:52And what these tables really
34:54show here is that the real.
34:57In the real world,
34:58only 11% of patients would have
35:01technically been eligible for L
35:03mind and hence they wanted to see
35:06whether this this difference in real
35:08world versus the the trial data,
35:11does that lead to any change in outcomes?
35:14And as we know,
35:16the reason this is a pertinent
35:18question is because in 2020 FDA
35:21gave an accelerated approval to
35:23tafflin in patients with relapsed
35:26refractory DLBCL including transformed
35:28DLBCL who are not eligible for
35:31autologous stem cell transplantation.
35:34So these are the curves with a median PFS
35:38of 2.1 months and median OS seven months.
35:42So clearly.
35:45It leaves a lot desired and these
35:49data don't correspond with the
35:51trial data mainly authors conclude,
35:54because of its use in the real world,
35:57which is not in congruence with the patient
36:00population that was studied in mind.
36:03So I think this trial,
36:04this study is a good reminder
36:06to look at patient population
36:08for these trials and make sure
36:10that we are using this patient,
36:12this clinical option.
36:14In an appropriate setting.
36:19The next abstract I wanted to focus
36:22on is the abstract number 555 risk
36:25of CNS involvement and high grade
36:28B cell lymphoma with Mick and BCL
36:312 rearrangements analysis of a
36:33population based cohort with routine
36:36fish testing in British Columbia.
36:38So as we have discussed in previous
36:41ASC PME is there is a flurry of data
36:44coming out although I'll be all
36:47retrospective but with very high numbers.
36:50With high confidence that that we we
36:54don't necessarily have good effective
36:57strategies for CNS prophylaxis and
37:00this particular study is focused
37:02mainly in high grade B cell lymphomas.
37:04So they have these two subgroups
37:08based on pre fish like.
37:11So the present subgroup is what
37:13they call where prospectively the
37:15fish testing was done and the
37:17historic subgroup is where they had
37:19to do retrospective.
37:20Because in from 2005 to 2010 it was
37:24not standard of care at that center.
37:27And as you can see here patients,
37:30these are all with high risk disease and
37:33CNS prophylaxis was given in this fashion.
37:35So 40% did not get any CNS
37:38prophylaxis intrathecal therapy for
37:4051% in the presence of group and
37:449% with intravenous prophylaxis.
37:46So the authors show that the risk
37:50for CNS relapse for this high risk
37:53or high grade B cell lymphoma is.
37:57Around 6%,
37:58which is clearly a significant percentage
38:02and higher than more low risk DLBCL.
38:06They show that CNS IPI scoring is
38:08still relevant in this current era
38:11even in hybrid we sell lymphomas and
38:13the high CNS IPS score is is able
38:16to identify patients who are at a
38:19higher risk for CNS relapse, but then.
38:22When we look at all patients in
38:26this subgroup in this study,
38:29whether they received CNS prophylaxis or not,
38:32it really didn't change the
38:35cumulative incidence of CNS relapse.
38:38And even when I looked into the
38:41subpopulation of high CNS IPI score patients,
38:44we still did not see any difference
38:47between patients who received CNS
38:49prophylaxis versus who didn't.
38:52Of course, um,
38:53I wouldn't make too much of this
38:55particular curve of CNS prophylaxis
38:57by modality of treatment,
38:59but clearly goes to show that.
39:03The common perception that intravenous
39:06therapy is potentially a better
39:09strategy is probably not true,
39:12and we need more trials to identify
39:15more effective CNS prophylaxis regimens.
39:21Next, umm and my last abstract for
39:25this meeting is abstract #1 which
39:28was a plenary session paper which is
39:31the efficacy and safety of ibrutinib
39:33combined with standard first line
39:35treatment or a substitute for autologous
39:37stem cell transplantation in younger
39:39patients with mental cell lymphoma,
39:42results from the randomized triangle
39:44trial by the European MCL network.
39:49This particular trial included MCL
39:52patients who were previously untreated
39:55with stage two through 4 disease who
39:58were younger than 66 years of age,
40:00and of course they were suitable for
40:03transplant or and hydros chemotherapy with
40:07ECOG performance status of 0 through 2.
40:10The primary outcome being
40:12failure free survival.
40:13So it's important to understand how the
40:15trial was designed between the three arms.
40:17So arm A is.
40:19So in all the three arms,
40:21the backbone of chemotherapy was
40:23anthracycline containing and cytarabine
40:26containing regimen archtop Rd.
40:28have alternating for a total
40:31of three cycles each.
40:33And then the difference between the two
40:35arms is based on whether the patients
40:38received autologous stem cell transplant.
40:40Um um.
40:41Yeah.
40:41Or versus patients who did
40:43not receive autologous stepsis
40:45transmit and only received two
40:48years of ibrutinib maintenance.
40:51The first arm did not receive a brute
40:54nib along with the R Chop rdhap versus
40:58these two arms received ibrutinib
41:00as part of the chemo regimen itself.
41:03And important to note which is talked
41:06about less when we talk about this
41:08trial is that our maintenance was
41:11added following national guidelines.
41:13In all three trial arms,
41:14so many patients,
41:15actually almost half of the patients in
41:18each arm received rituximab maintenance,
41:21which is currently what we use in clinic.
41:24So I would say that in all these arms,
41:26especially in these two arms,
41:28it was R + I maintenance for the most part.
41:33These are the patient characteristics.
41:36So I just wanted to point out that
41:38most patients were stage four
41:40approximately almost 90% in these three
41:44arms and 58% of patients were low,
41:49maybe around 30% were intermediate
41:51and 15 to 16% of high maybe patients
41:55were included in this trial.
41:59And these are the important
42:01curves out of this plenary session
42:03paper of failure free survival.
42:06And you can see that the arm where
42:10patients received our chop Rd.
42:12have followed by autologous stem cell
42:14transplantation had an inferior failure,
42:16free survival in contrast to
42:20ibrutinib containing arms.
42:22Now we need more time before we
42:26can tease those two cars out, but.
42:29Clearly we can say that addition
42:33of ibrutinib makes autologous
42:35stem cell transplant less relevant
42:37in the frontline setting.
42:39So that's pretty much the
42:42take away out of this.
42:44Study.
42:45And that difference between
42:48overall survival of ibrutinib
42:50containing arms versus non
42:53ibrutinib containing arms is clear.
42:55So the authors conclude that it overall
42:58too early to evaluate statistical
43:01significance of overall survival.
43:03But there is definitely a very clear
43:07signal that ibrutinib containing regimen,
43:10we may be able to avoid autologous
43:12stem cell transplant consolidation
43:14in those patients as long as they
43:16are able to receive it routine
43:19maintenance with or without rituximab.
43:21So authors conclude that A+
43:23IR is superior to a.
43:26The autologous stem cell transplant
43:28is not superior to ibrutinib
43:30containing regimens and currently
43:32no decision whether autologous stem
43:34cell transplant adds to ibrutinib.
43:37But toxicity favors ibrutinib only
43:40and numerical overall survival benefit
43:42was seen in the ibrutinib arms.
43:46So this is my summary slide.
43:48For mantle cell lymphoma and
43:50large B cell lymphoma, our job Rd.
43:53HAP with ibrutinib followed by
43:55ibrutinib with or without a taxman.
43:57Maintenance is an effective frontline
43:59strategy in young and fit MCL patients.
44:03Autologous stem cell transplant could
44:05be safely avoided with this strategy.
44:08Clinically available biomarker driven
44:11strategy to escalate traditional immuno
44:14chemotherapy could potentially help improve
44:16outcomes in high risk large B cell lymphoma.
44:20Addition of Bortezomib to Archtops shows
44:22improved outcomes in ABC subtype of DLBCL.
44:25In my opinion it would have been practice
44:28changing if gene expression profiling
44:30was readily available clinically which
44:33is which is not the case at this time.
44:36Lab Pi prognostic model,
44:38which includes LDH anemia and beta
44:412 microglobulin, is a cheap,
44:44reproducible and effective tool that
44:46could be useful in some countries
44:48and in some clinical settings.
44:50Polarized followed by autologous
44:51stem cell transplant consolidation
44:53is an effective second line regimen
44:55with good outcomes.
44:57This off label regimen can be potentially
45:00considered in patients with transformed
45:02DLBCL who would not have otherwise
45:05received polar in the frontline setting.
45:07Tafa Len may be optimally suited
45:10only for patients with fewer prior
45:12lines of therapy and non refractory
45:15disease so that it reflects Elmi
45:17and clinical trial population.
45:19And lastly,
45:20currently utilized strategies for
45:22CNS prophylaxis in high grade B
45:25cell lymphomas are ineffective
45:27and more studies are needed.
45:29Thank you so much and now I'll pass
45:31on to Doctor Sethi to drive US home.
45:40Thank you Doctor uh Qatari for
45:42the excellent presentation, so.
45:46Let me just.
45:50Can you see my screen?
45:53We can see your PowerPoint. Yeah,
45:55you can just share your slides.
45:59OK, here we go. All right.
46:03Perfect. OK. Thank you. Alright,
46:06so I will be focusing on 2 cell
46:08lymphoma and Hodgkin lymphomas.
46:12So for the T cell lymphoma abstracts as
46:15well As for the Hodgkin lymphoma abstracts,
46:18my selection is most
46:21focusing on immunotherapies.
46:23Both in both the diseases.
46:26So starting with the first abstract,
46:28it's a phase one trial using nivolumab
46:32in combination with dose adjusted
46:34epoch in newly diagnosed PCL.
46:37This was an investigator initiated
46:39study by Doctor, Hamaker said.
46:41University of Colorado,
46:43so we know that those are just the
46:46Deepak is available treatment option
46:47in the first line for peripheral T
46:50cell lymphomas regardless of subtype.
46:52However, we also know that.
46:57With anthracycline based therapies 25% of.
47:00The five year old PFS in PCL is just 25%.
47:06So there is a great need to
47:08improve upon these under cycling
47:11based regimens in the first line.
47:14The issue with the immune checkpoint
47:16black blockade in T cell lymphomas
47:18is that there has been a risk of
47:21hyper progression noted in certain
47:23subtypes like specifically atll.
47:25Single agent immune checkpoint
47:27inhibitors had an overall response rate
47:30of 30% in heavily pretreated patients.
47:32But again single agent therapy in T cell
47:35lymphomas is not really the way forward
47:38because of the risk of hyper progression.
47:41So this particular study wanted to look at.
47:46The combination of cytotoxic therapy,
47:48uh immune checkpoint and ambition
47:50in the hope that the tissue injury
47:53from chemotherapy will result
47:55in new antigen expression and
47:58increased tumor immunogenicity.
48:00So umm.
48:01Also in PTCL there is.
48:14And we need more treatment options and
48:16the other thing is that the with the
48:19immunosuppressive microenvironment and
48:21high mutational burden there is a. Risk.
48:24Uh, there is a, you know, viable, uh,
48:27reason why this would be effective.
48:33So we looked at the combination of nivolumab,
48:36so the and epoch in this study and.
48:41The they use the flat dose
48:43of nivolumab and the standard
48:45dosing of dose adjusted epoch.
48:48And they allowed those levels
48:49starting at those level minus one.
48:53So here, uh, the main thing I want
48:55to focus on is that they included
48:57a number of different subtypes,
48:58also including primary cutaneous
49:00gamma delta T cell lymphoma.
49:02It is a an uncommon rare subtype.
49:05However, you know this is something
49:08we do come across in clinical
49:10practice and I'm highlighting that
49:12because they found some durable
49:14responses in this population.
49:16So as expected patients did have
49:18a number of immune related side
49:20effects and here at least one
49:22patient had each of one of these
49:24that you can see in this figure.
49:27What they found was that the immune related
49:30side effects occurred early and that.
49:33A did lead to stopping new nivolumab
49:38and these you know in the in a
49:41subset of these patients because of
49:43the immune related side effects.
49:45What was really interesting
49:46was since the study did allow a
49:49previous cycle of chemotherapy,
49:50what they found was that the
49:52patients who had previously received
49:54chemotherapy and where the combined
49:56combination was initiated as
49:58cycle two rather than cycle one.
49:59These patients had very few immune
50:01related side effects and treatment.
50:03Continuations.
50:04So this strategy did somehow it was
50:09like it was not really a planned thing.
50:11It was just because these patients ended
50:13up starting with cycle two that they
50:16did find fewer immune related side effects.
50:18So a potential strategy for future studies.
50:23What they also saw that was that even
50:26though the the toxicity was seen early
50:29but a number of patients with both PR.
50:33As well as stable disease did did
50:36convert into ACR at the end of treatment.
50:39So necessarily the treatment was
50:42not you know the treatment as it was
50:46continued late responses were seen.
50:48Uh, here's the UM survival analysis curves.
50:52Uh,
50:52so the at a median follow-up of
50:54about two years,
50:55the median progression free survival was.
50:59For 34 days and overall survival
51:02was 714 days.
51:05They did not find any
51:07obvious predictor of outcome,
51:08so including an I think on the NGS
51:11panel or PD1 PDL one expression.
51:14So there were no clear markers
51:17of predictive of response.
51:19So basically uh,
51:21the things that they highlighted
51:23was that in this particular scenario
51:25there were no hyper progression events
51:29which is reassuring considering that
51:32single agent checkpoint inhibition
51:35is really something that we worry
51:38about immune related side effects did
51:40occur early and then as I mentioned
51:43people who had had prior chemotherapy
51:46did do better in terms of tolerability,
51:49tolerability of.
51:50Meanwhile, the man.
51:52So there were at least two
51:54patients who had durable responses
51:56in Gamma Delta T cell lymphoma,
51:58which is traditionally thought
52:00to be very aggressive.
52:01And so that again is I think.
52:06One of the reasons that you know,
52:07checkpoint blockade is still being
52:10investigated and RTL inform us.
52:13In the hope of, you know,
52:14finding a particular disease
52:17subtypes that would respond.
52:19So the next paper again is also
52:21in the main checkpoint based
52:22combination and this one combines
52:25pembrolizumab and romidepsin.
52:26The prior study was in the front line,
52:28this is in relapsed refractory lymphoma and
52:31this was this is study out of MD Anderson.
52:35So basically again as we mentioned
52:37there is a even though there is
52:39a risk of hyper progression,
52:41there is still reason to study immune
52:44checkpoint inhibitor is in cell and formulas.
52:46And in this particular scenario
52:49they wanted to combine it with
52:51an epigenetic modifier that is
52:53romidepsin which is an HDAC inhibitor.
52:56There is a preclinical data for possible
53:00synergy that's because HDAC inhibitors
53:02do increase PDL one expression and.
53:05So they think that they can,
53:08um, the addition of.
53:12Checkpoint inhibitor will uh.
53:14Promoting will basically in these patients
53:19can help with the improved responses.
53:22So in this study design they had a
53:25phase one lead in for six patients
53:27for as a safety cohort and then they
53:30went ahead with the phase two cohort
53:33and ROMIDEPSIN is traditionally given
53:35day 1815 in this particular study it
53:38was given only on day one and Day 8.
53:44I just hear want to highlight that they did
53:47include a subset of patients that had TFH.
53:53Histology like a ITIL which traditionally,
53:56and this subset of patients usually
53:58responds well to romidepsin.
54:00Um, again, they did have two
54:02patients who had hyper progression
54:05in this particular, OK, so that is.
54:09But again it was a minority of
54:13patients when considering you know
54:15that scene with single agent versus
54:18combination of checkpoint inhibition.
54:21The overall response rate was
54:2347% with the CR rate of 37%.
54:26Again, this was a repeated
54:29heavily pretreated population,
54:30so these are not unexpected numbers and.
54:35This is a Sankey plot that just shows that,
54:37as you can see here, the TFH histologies,
54:39uh, many of them did respond and
54:42get CR after getting Pembroke Romi,
54:45but the response is not,
54:46as you know,
54:47uniform and so some of the other subtypes.
54:52So, uh, the median overall survival in
54:56this cohort of patients was 21 months and.
55:00And the median PFS was 4.8 months with the
55:05median duration of response of 36 months.
55:08So basically what they found was
55:11that even though by absolute
55:12numbers it may not seem high,
55:14but for T cell lymphomas in this scenario,
55:16it did lead to meaningful response
55:18with high response rates and so
55:20they have a larger phase two study
55:23based on this as the next step.
55:27So the next study that I'd
55:29like to highlight was actually
55:31presented by Doctor Francine Foss.
55:33This is a registration trial
55:36for EQUAD for EQUAD 7,
55:38which is an improved formulation of
55:42Deniliquin DeVito X, which is on that.
55:45And this included patients
55:48of relapsed refractory CTCL.
55:50So on tag is a recombinant
55:52protein that has the period toxin
55:54and the human interleukin 2.
55:59And.
56:02Contact was previously taken off the market
56:04because of manufacturing issues in 2014,
56:06so this is an improved version of this.
56:10So basically it has uh two
56:13different uh ways that it adds it.
56:15There is direct uh tumor
56:17cytotoxicity by the ill,
56:192 attacking the attaching to the tumor cells
56:24and the diphtheria toxin acting as the.
56:27Acting as basically the uh, uh,
56:29active agent and then it also
56:32affects the T regs in which.
56:35Required seven is actually
56:36decreases in the number of T Rex.
56:38So it's being thought of as a,
56:40it is actually as an immunomodulatory agent.
56:47So in this particular case,
56:48you know we primarily included
56:51patients with city 5 positive,
56:55CD, 25 positive tumor with CCR.
56:59In relapsed refractory cases.
57:03So in terms of response rates,
57:05I just you know it showed the response
57:08rate was kind of dependent on stage
57:11and most of the responses were seen
57:13in early stage disease with an
57:16overall response rate of 36 to 45%.
57:20This just shows you, you know,
57:23the one of the things we assess
57:26disease responses msport with
57:28looking at the skin tumor burden.
57:30And here we see that the maximum,
57:34you know response again was seen in
57:3748% patients with the 12% achieving CR.
57:41Um, and this swimmers plot
57:44is just delineating.
57:47About 20% patients had prolonged
57:50responses of more than one year.
57:53The main side effects were expected
57:54side effects that are the IL,
57:56two related side effects like
57:58capillary leak syndrome and peripheral
58:00edema as well as some transaminitis
58:03and infusion related reaction.
58:05So again you know overall this is
58:09an active agent in CTCL and again
58:13it is a possible improvement over
58:15on tag and this was a registration.
58:1730 and it has been.
58:20The initial application is accepted
58:23for approval for review.
58:27So I think at this point it's uh,
58:29since it's one o'clock, I'm going to.
58:33Stop here.
58:35And basically the Hotchkin you know cases,
58:39the abstracts that I wanted to talk
58:41about were nibo ice that was found
58:43to be pretty effective in high
58:44risk Hodgkin lymphoma patients.
58:46And the other one is a combination
58:48of a newer agent and anti lag 3
58:51antibody with with pembrolizumab and
58:54but in the interest of time I will stop here.
58:57Thanks.
58:59So I wanted to thank all three of the
59:02panelists for really selecting highest
59:04priority and impact abstracts and doing a
59:06great job summarizing that all panelists
59:09are able to stay for a few more minutes.
59:12And so I thought we'd have a little
59:13bit of question answer period,
59:15some great questions coming
59:16in from doctor nepotism.
59:17But first I I had a question
59:20for Doctor Motonari.
59:22You know with the augment long term data
59:24and with really encouraging data with by
59:26specifics a lot of patients with locular,
59:29the non high risk patients are
59:31actually getting rituximab first line
59:33R chemo often our vendor second line.
59:36And how do you think about third
59:38line for those patients?
59:39Do you think about our square,
59:40do you think about bispecific,
59:42how do you,
59:42how do you actually you know without the
59:44data we don't really have randomized data.
59:46How are you going to approach those cases
59:48which will be actually quite common.
59:51Very good question and I think this
59:54is by just my my personal opinion,
59:56I don't think we're going
59:58to be given data on the.
01:00:01The sequential treatment meaning
01:00:03what would be the outcome in patients
01:00:05receiving our square as second line and
01:00:08the patients followed by by specific.
01:00:11Most of the clinical trials that are
01:00:14now ongoing tend to combine our square
01:00:17with the with or without The Dirty
01:00:19taxi with the by specific antibody.
01:00:22So you know when we combine these treatment
01:00:25we always get into a little bit more
01:00:28toxicity and I'm not sure that all.
01:00:31Nations that would benefit from an
01:00:34intensification of treatment earlier
01:00:36on uh what we really need is good
01:00:39prognostication model to really
01:00:41risk stratify these patients up
01:00:42front and guide us in the selection.
01:00:45But for now I think it would be
01:00:47content to just the sequence,
01:00:48the treatment that they are available
01:00:51with our square followed by a
01:00:53by specific antibody.
01:00:54Certainly after reviewing this
01:00:56data card in my mind is pushed a
01:00:59little bit over in the future for.
01:01:01Participation population.
01:01:04Yeah, I think that's a really
01:01:05helpful response and exactly
01:01:06what I'm thinking as well.
01:01:07There may be some slight, you know,
01:01:09select patient populations where you have
01:01:11toxicity concerns whether it be renal
01:01:13dysfunction with line things like that.
01:01:15But the R-squared data is quite compelling
01:01:17with that particularly that freedom
01:01:19from next treatment of 70 months.
01:01:21So I I think that sequence is here
01:01:23to stay at least for the time being.
01:01:26There's a important question to to all of us,
01:01:31but really directed to Doctor
01:01:32Cathari about what's you know,
01:01:34where do we go with.
01:01:35First line DLBCL in 2023,
01:01:39you know we'll likely hear about Paul R Chip,
01:01:42but I thought your data actually
01:01:44of using our chop and then epoch
01:01:46and then giving some centering
01:01:47was quite compelling for the the
01:01:49high grade double hit patient.
01:01:51So how how are you thinking about
01:01:53approaching your non double hit
01:01:55and double hit patients in 2023?
01:01:58Yeah. Very difficult question to answer,
01:02:01mainly because we don't have direct data,
01:02:05but we can put few pieces together and
01:02:07come up with a treatment plan, I guess.
01:02:10So my strategy would be that if the patient
01:02:13is a denovo DLBCL with IPI score of three
01:02:17to five and it does not have a double
01:02:21hit disease or double expressor disease,
01:02:23then I would still be more,
01:02:27you know, favorable.
01:02:29Favor of Pola RCHP.
01:02:32If it comes to a patient where we
01:02:34are worried about double expressor
01:02:37and double hit disease.
01:02:38I I I would think that you know I would
01:02:41definitely put in a lot of weight to this
01:02:44dose escalation strategy where there
01:02:46is incorporation of high dose methotrexate,
01:02:48there is incorporation of R epoch
01:02:52followed by hydro cytarabine.
01:02:55I think the data is very
01:02:57compelling as you said.
01:02:59In and I think Doctor Nepri
01:03:01also asked regarding how I,
01:03:03how I would approach subgroups
01:03:05of these DLBCL.
01:03:06And you know at at in this current
01:03:11time all so far all the trials that
01:03:14were designed to primarily study
01:03:17these subgroups have been negative.
01:03:19So for example Phoenix trial very
01:03:22compelling results when you you know
01:03:24further tease out these molecular subgroups
01:03:26for example in the Phoenix trial.
01:03:29MCD subgroup did phenomenally well
01:03:31when ibrutinib was added to our chalk.
01:03:34Similarly the data that I presented of
01:03:38adding Bortezomib to our chop in ABC DLBCL.
01:03:41But the reality is that in clinic
01:03:44gene expression profiling is very
01:03:46challenging to do and I think we really
01:03:49need to put in a lot of effort as
01:03:51as as a group of clinicians to have
01:03:55better clinical modalities to to.
01:03:59Risk stratify patients by gene,
01:04:02by genetic makeup in the clinic,
01:04:06if not by diagnosis then at least
01:04:08by the end of first cycle,
01:04:10so that we can change strategy
01:04:13second cycle onwards.
01:04:17That's really helpful.
01:04:19And and I guess what you're getting at
01:04:21is a dynamic biomarker whether it be
01:04:23you know self for DNA and and or kind
01:04:26of reduction in the circling disease.
01:04:28There's a question from the audience.
01:04:31It kind of I think broadly in inductive
01:04:34Montanari kind of alluded to it
01:04:36trying to think about by specifics
01:04:38versus cellular therapy car T tarsin.
01:04:40Can you help us with you know that
01:04:43thought right now it's really just in
01:04:45follicular but certainly there will be
01:04:47more data with bispecific and large Sonoma.
01:04:49How do you how do you kind of think
01:04:51about those modalities for your patients?
01:04:54Yeah, I think right now it's
01:04:56such a dynamic field and which
01:04:58is which we are thankful for to
01:05:00have all these different options.
01:05:01But I would think that you know
01:05:04Carter cell therapy I think in
01:05:06is definitely more involved.
01:05:09And also there's often a delay because
01:05:12there's no still the options we have
01:05:14are not off the shelf uh options.
01:05:16So there's a delay in you know
01:05:18getting these patients to treatment.
01:05:19So I think having the option of bias
01:05:22specifics really I really don't think
01:05:24that one would replace the other.
01:05:26I really think that they are both important,
01:05:28but I think having the the option of
01:05:30by specifics as as an off the shelf
01:05:33option will avoid the delays that we
01:05:35usually see and then also would be
01:05:37reasonable options for maybe even older.
01:05:39Individuals that sometimes are not
01:05:42candidates for Karti cell therapy.
01:05:46Yeah, it's it's clear that by
01:05:48specifics are being moved up
01:05:50earlier into first line,
01:05:51so follicular pharma for large volume comma.
01:05:55So you know I was reminded that it's
01:05:57actually it was 25 year anniversary of
01:06:00rituximab being approved and to think
01:06:02about in the last three years all the
01:06:05biospecifics being developed and how
01:06:06fast this is moving is pretty remarkable.
01:06:08So I'm sure we'll have lots of
01:06:13dents CME post ash meetings.
01:06:16For the coming years as well,
01:06:17but I want to thank our presenters and
01:06:19and thank all of you for joining and
01:06:21I hope everyone has a great weekend.
01:06:25Thank you.