Yale ASH 2022 Highlights: Lymphoma

Transcript

• 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&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.