CAR T-cell therapy has revolutionized treatment for relapsed/refractory non-Hodgkin lymphoma (NHL), with response rates of 75-92% in clinical trials, but faces significant implementation barriers including high costs, limited manufacturing capacity, complex regulatory processes requiring navigation through multiple committees, and the need for specialized referral models to ensure equitable patient access. The therapy is now being used earlier in treatment algorithms, even before second-line therapy for patients with early relapse, and has shown efficacy across various NHL subtypes including diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, with real-world outcomes comparable to pivotal trial data.
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CAR T-Cell Therapy in NHL: Redefining the Therapeutic Landscape
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Thank you Kushid. A very good evening and good afternoon everyone. I'm Dr. Nidra Gupta uh from Immunil Therapeutics and I head clinical development and medical affairs at Immunil.
from on behalf of Imunil. It gives me immense pleasure and privilege to welcome all the distinguished speakers, faculty members and participants who have joined us today to this scientific meeting and international webinar speaker webinar.
I'm deeply honored by the presence of internationally and nationally acclaimed uh specialist hematologist oncologist uh to this meeting whose pioneering work has shaped the landscape of hematology and blood cancer treatment. It is deeply honored to have you with us. We we want to it's a testament uh to the global collaboration that we have your presence and your willingness to participate, exchange your experiences and share your expertise in this meeting. We really look forward to an exciting discussion, thoughtprovoking presentations and an enriching experience. As an international speaker, we have Dr. and Alisa with us and the chair for this program is none other than Dr. Pankage Malotra. He is the professor and head at uh clinical hematology and uh the BMT unit at PGI Chindigar. Uh sir will be talking about setting the context with evolving landscape of cardi cell therapy in India. So we have innovation in house and how do we shape this landscape in terms of blood cancers? We'll hear out from Dr. Panka sir. Dr. Pang over to you sir.
Okay. Thank you. Thank you Dr. Nra. Uh greetings uh from TG Chandigar.
So uh let me share my slides.
Are my slides visible?
>> Yes sir, it is visible.
>> Okay. So, uh thank you so much again. So my job is uh just to give a overview of uh landscape of CT cell therapy in India. And not very long ago uh there was a research paper in cytootherapy about the carti cell therapy in India requires a paradigm shift in training education and healthcare processes. So in this article they actually discuss about uh what are the challenges uh which the uh physicians in India are going to face. Uh uh and in this uh research paper they actually mentioned about the need uh of uh uh how many patients probably would require a carti or the cellular therapies. uh so close to uh 110,000 uh patients in India are diagnosed with uh acute leukemia uh or lymphoma and uh they actually showed a chart where they showed the bone marrow transplant centers probably uh in this chart they mentioned only about uh 30 odd or so transplant center but right now I can give the information in 2026 there are close to 180 transplant centers in India. India who are doing autologus and allergenic and probably all these uh centers are equipped to do a cartisel therapy also. So these were the challenges which they mentioned and uh uh I'm not sure whether you know it is very much visible or clear from this slide or not but they basically mentioned about the limited availability logistics and uh uh all those challenges and one of the major challenge in India is because uh this has never been any kind of a cell and gene therapy in India. So even the government regulatory authorities are not very clear how to give permission. So uh you know they mentioned about the list of regulatory committees and you can see that there are at least 10 committees uh you know through which you have to go through uh if you are planning to do a carti or a cell and gene therapy in India. So you know starting from the ethics committee, institutional biosafety committee, review committee of genetic manipulation, BCGI, central drug research organization. So so this is I think a one one of the major challenge because we know that once you submit any any kind of a proposal if it is going to through the 10 committees obviously it is going to take uh you know many many years before uh you know you get the clearance.
In 2023, we uh actually did a survey of uh uh uh of the physicians who are involved in the transplant uh at the Indian society of bonuro transplant center meeting and we looked at the what are the unmet needs and potential barriers for carti cell therapy in India and I'll just show one u uh one cartoon where you know when we did the survey so most of the physicians said probably they would see one to 10 patients probably would be eligible to undergo a cartis cell therapy and all the physicians mentioned the cost and finances to be the major part and uh you know even though as I would discuss in my subsequent slides that even though you know we have two carti cells which are available in India but and even though they are a fraction of the cost what is available in the western countries but still the cost is the major factor in uh uh you know in giving the large access to the patients who require a cartis cell therapy and this is one of the review article which we published about the advance in vaccine checkpoint blockade and cartis cell therapies. So the evolution which has happened uh in India how the cartis cell came and uh I thanks the mun to providing me this slide. So in the phase one research uh uh and uh uh discovery took place in IIT Mumbai with Tata Memorial Hospital Mumbai and this happened in 2003 to 2018 when I immuno act the company was uh founded.
then followed by uh the phase two uh where the clinical translation and indigenous clinical development and manufacturing capability creation was done and IND was filed in 2020 during the covid times and then there was a commercialization which happened after the phase 1 and phase 2 trial. The first patient was treated in 2021 followed by the uh the first car approval which is called next car 19 in 2023 and followed by in 2025 the quatti uh which got the approval and then you know more than currently more than 500 patients have been treated all over India with these therapies and uh obviously there is a need to do a global expansion of all these therapies. This is one of the paper which was published in blood cancer journal on the pediatric uh alll uh about the maxar or teley capta gene and here the response rates uh you know at 1 month was close to 90% or so uh around 66% or so complete response and partial response in 25% or so and the response to carti in uh relapse or refractory visel malignancies this includes the adult patients where lymphoma and leukemia work for there and the response rate were close to 75% or so uh at 1 month or so and this is immunil product war vney captigene autoel in relapse refractive visel malignancies which is published this year and here again at 1 month the response rate was 92% or so and almost 83% of patient had a response uh even at 3 months uh time.
So when you look at the implementation of cartis cell therapy program in India uh there are many challenges uh and you know the first challenge obviously as I mentioned previously there's a huge unmet need for a cartis cell therapy in India and currently the guesswork is that at least 30,000 patients require uh a salvage therapy with cartis cell in India every year the key barriers obviously are high cost even though you know I said currently we have a fraction of cost uh uh then is as compared to the west but still this cost is for most of the Indian patients who belongs to low and middle income is high. There is limited manufacturing capacity, logistic barriers out of port pocket expenses or so. The expanding manufacturing capacity uh is there but it is still you know uh limited.
we require a tailored pre-infusion uh bridging therapies for all these uh patients or so and post-infusion care strategies we require effective management protocol for CRS or uh IECS or IC and infections uh which are quite common in in the Indian setting.
uh however we have a unique uh research potential in India because of the limited exposure to bicep specifics like glita or lina and other uh imunotherapies. Uh so uh and obviously you know in future we require actually both the bicep specifics as well as the cart cell therapy and currently the world is uh you know looking at how best to use uh these form of therapies uh how best to sequence these therapies uh in the care of the patient.
So uh so there are editorials which mention about how do we go about democratizing the cure of indigenous innovations and future of uh periodic cell and gene therapy but the other therapies also. So two therapies uh which are already approved the next car and quatti. Uh the CD19 periodic alll is uh uh you know going on in CMC law. BCMA carti for uh for multiple myoma is in the pipeline currently in phase two or so and then there are triricarti cell therapy and third and four fourth generation carti which are coming and dual cd 19 and cd 22. So overall there are 9 to 10 carti cell therapies uh uh program which is going on in India and hopefully in the next couple of years we will see more cartis coming up in India.
So this is the roadmap for achievement of equitable patient access to the cell and gene therapy in India. We have to have a good foundation and the most important is the government funding and incentives and uh minimizing the uh you know the approval uh committees you know so we require only probably only one committee or so which can approve this therapy and then we need a building blocks like local manufacturing skilled workforce and GMP facility and so that you know if we have all these then we can have an equitable patient access affordability treatment long-term follow-up of these patients. Uh so okay this is this is in brief uh uh about the road map of cartis cell therapy in India. Thank you so much for giving me this opportunity to participate in this uh discussion and over to panel discussion. Thank you so much.
>> Thank you. Thank you sir for that insightful overview on the evolving landscape of cartisel therapy in India.
So building on this perspective uh it is equally important for us to understand where we stand globally and how international experience can guide us forward. So before we move to our next topic it is indeed an honor to introduce our esteemed speaker for today's webinar professor Analysa Ruggi. Professor Analysa is a senior consultant at the hematology and bone marrow transplant unit of the San Rafael Scientific Institute in Milan, Italy. She's also the head of cell therapy at our institute. She is also the scientific chair of the Euroord office in Paris and the secretary of cellular therapy and immunobiology working party of the EBM.
She has authored more than 200 peer-reviewed publications and also has participated as an invited speaker at many international conference such as ASH uh European Society of Hematology and EDMT. Over to you professor and >> thank you very much and um good afternoon good evening to everyone.
First of all I wish to thank uh all of you for the kind invitation and Dr. people set for the longlasting collaboration and uh the opportunity to show the indication and the main um activity of the EB&T in the setting of cartisel therapy in the nonog and I have to say that I'm very honored to speak to your community not only because I love your beautiful country but also because h as from the European point of view is the number of patients and the resources allocated are extremely different. So all the effort done for implementing the academic research and having your own product for your patients is really uh such an amazing objective and congratulation for all your um contribution for for the cell therapy in a patient with lymphoma.
So uh I think may I go uh with my with the slide or you can you can go probably I I I cannot >> you you would have the controls uh professor so you can keep moving the slides >> I'm not I'm trying oh okay so pro it's probably me so okay so we can stay in this slide just to show uh these are the data from the EB&T registry according according to the last um publication on and data cut off of March 2026 showing a clear uh constant increase in the number of patients transplanted and the number of patients receiving cartis cell therapy for the different uh the different indication.
Uh it is important to know that um uh patient are uh growing not only in the main diagnosis the amatological malignancies but also in the setting of other indications such as the autoimmune autoimmune and we will see briefly later on but I cannot go out uh the slide don't move so I don't know why can you go to the next slide side.
Thank you. And this is the actually exactly to this one. We have the the following one. We have a a constant increase in the number of KT per year approaching more than six 6,000 per per year reported. uh reported to to the to the to the registry and as I was mentioning of course nonoginform remain the main the most important indication for transplantation and we will see how also the treatment is changing according to the different line of therapy but also other indication such as the imun autoimmune autoimmune disease and this is of extreme extreme importance Uh so just previous one the previous one. So looking at no okay next one.
Okay so focusing on lymphoma which is the topic of our talk today. Uh we had um according to the FDA, EMA and also the national authority in Italy, we had a clear change in with the main trial and the approval uh from from the different from the different treatment.
So there are nowadays several different products available in in the market with different indication and we will see how also the toxicity profile of each product is changing allowing to choose and select the best product for instance for the frail patient or for those with the more ben and um according to the main main character istics. So we can uh see next slide how the different product that were the mainstone for the different indication where of course the first product appro approved in the setting of alllastic leukemia of B origin in young patients up to 25 years old and then the changes in the setting of nological lymphoma.
first in the primary mediastinal bell lymphoma in third line and then diffuse large bell lymphoma with first um after two lines of therapy and nowadays even before the second line the second after the second line of therapy for patients with an early relapse within 12 months after the first line and then of course the different product available for montel lymphoma and for follicular lymphoma of Of course for patients with um nonog lymphoma diffused large bell lymphoma we know how the prognosis is extremely poor looking at the disease status. So the primary refractory or those relapsing very early after an autotoous stem cell transplantation or after second line. So uh despite the rate of cure that we can obtain with the first line uh still uh there is um there is a huge a huge amount of patients relapsing for whom the second fther treatment is is is needed. Uh next slide please.
So when we look at the carti in patients with lymphoma more than second line, we had the different product associated with the main trial named the zuma one with the product which is the axisel tel the juliet and the transcend for lizo cell. The three product are nowadays in commerce available and it is clear that is important how the costimulator domain is extremely is is one of the key for the efficacy of the treatment and also we will see how it drives also some of the uh of the different of the different toxicity toxicity profile. Uh next slide please.
So uh this is uh the following slide reports a little bit the main uh different uh tri results of the different trial. So patients that are selected for being allocated in h in the different in the receiving the different product and here it is important to know how according to uh the main product. So the axis cell, ta cell and the lizo cell. Of course, it is also important to consider that uh the progression pre- survival and uh the um the disease the disease preserval varies according to uh the time also for response and the different criteria showing of course also a different toxicity profile. H looking at the detail report and in the table in the um in the lower part of the of the slide I show I clearly indicated the level and the incidence of any grade of adverse event namely CRS and icons showing how this um is clearly related to the product. We know that with axisel and the main characteristics of the product is associated with higher risk of CRS and differently than uh the other the other available products. However, nowadays and we will probably discuss later on about how it changed the management of the early complication especially the early CRS and icons. how it is nowadays less important in term of um h grade more than grade two. So the impact of the CRS also in the outcome final outcome namely the mortality is clearly uh reducing with the new uh with the new strategy for the management uh the management uh of uh of of the disease. Uh so the next slide please and the following one. Uh because of course patients included in the trial are uh of course very selected patients and well monitored patient. However there is also an important consideration to be done that is the comparison between those patients included in the clinical trial and what is in the real world. And we had uh since uh now several different publication, next slide please. Uh showing how uh the data reported in the clinical trial which are in the first side of the slide are clearly comparable with those reported by the registry analysis in which of course all the patients are combined not selected patient included in their trial. So clearly showing how it is reproductible. It is super impossible and the not only in the rate of um efficacy. So the progression pre- survival, the overall response rate and the clinical response but also the toxicity the toxicity profile namely the grade um three to four of CRS and icons. So um these are data both from the CIBMTR USA consortium and also and we had also important experience coming from uh national national registry such as the um the French national registry which clearly demonstrated how it is um it is super super impossible and and comparable with the data reported in the clinical trial. So the use of carti in patients with refractory to after second line changed completely the algorithm in in the treatment and of course the number of patients who are now receiving anos transplantation is reducing of course due to the h management and also the safety profile of the carti product.
Different products are available and of course several evaluation can be done when we select the appropriate treatment and Axis has been reported with a slight superiority in term of efficacy but also a higher cost of toxicity which nowadays is becoming more uh more manageable. I um I would I would say uh so it is it is really really important to consider and to be confident that those product can be can be used safely in the the second line after the the relapse of the second line. But um thanks to the opportunity of having this product early in line nowadays we had the possibility of use especially in the setting of diffused large bell lining those treatment even in patients relapsing after um after the first line of therapy. Please go ahead with the two slide. Uh next one and the other one uh um exactly the next one. uh so here is a quite an algorithm of what I was mentioning before because out of the patients that unfortunately relapse after the first line of therapy and 70% almost are early relapse within uh the first uh the first year and for the other patients half of them are not transplant eligible so they cannot be properly cured and even those who are transplant eligible, not all receive um a definitive cure after those those treatment because of course the incidence of relapse is still high also after uh after the first the first line.
So those patients who are in un ineligible for autogus and those relapsing early within the first year after uh after treatment face a very very poor prognosis. So looking on next slide please on what is the um background and the results of uh the application of uh the carti anticced 19 carti in the setting of diffus large bell lymphoma in second line. Of course, the results were extremely enthusiastic, namely in term of progression free survival and and progre and the overall survival showing how in comparison with the standard of care. Of course, there was a clear benefit of the treatment with uh with the um uh the the Garti treatment and this has been demonstrated by Zuma 7 which then allowed to the approval of uh this axisel in the specific patients as well the transform with the with the lysos. And again we had several different uh reports showing uh um showing uh how those data are confirmed by the real world data. Uh we had uh cases reporting um from the registry from the national registry namely the French and the UK clearly confirming how the incident of the toxicity is quite manageable especially in the setting of severe grade three to four CRS and and so whenever we look at the real world data and what is the results of the clinical trial, the results are consistent and the benefit of curing those patients with uh the cartisel therapy is really uh really clear and um impacting. So next next slide please. Uh so this these data uh clearly bring uh a new treatment algorithm for patients with the diffused large bell lymphoma in which for those patients relapsing early after the first line of therapy which again are the majority of those patients most frequently the young one associated with very severe disease they can be allocated for the use of carti in in second line and the Zuma 7 clearly demonstrated the benefit of Axis over second line chemo plus autogus and so therefore the benefit for cure. Of course, there are still a lot of place for the third line treatment therapy option and we will discuss during uh the next um the next um time the use of by specific and how this uh possibility of treatment can interplay with with the treatment algorithm for for um diffuse large B cell. Uh next slide please.
So regarding the follicular lymphoma uh of course follicular lymphoma is a different disease in which of course uh uh the there is a slower disease growth in the beginning with pfs events occurring later. uh but of course the incident and the possibility of transformation and therefore the aggressivity of the disease is still very very important. So those patients especially for those having um grade three follicular lymphoma the indication for the use of cartine has been demonstrated in the different in the different trial zuma five the transcend and even for for those for those patients we get the approval of the product in third line after uh the um clear confirmation of the benefit of Axisel in term of overall the response rate and um complete complete remission and also five year progression free survival of 50 reaching 50%. So again for patients with very high disease resistance disease again the possibility of achieving um cure definitive cure after after treatment is really really important and uh also these data were confirmed by the real world data uh uh which um were reported by the CIBMTR and by the French national registry.
showing prolonged the disease free survival and overall survival in patients with um both receiving a cell or tisa cell and again low profile of severe CRS and especially in in the patient with also with with axisel. So clearly showing how also the bi biology of the disease may be associated with a different safety profile of this of this product. So in in the setting next slide please. In the setting of follicular lymphoma um uh the the benefit and the um uh efficacy of the product seem really equal and of course axis seems to be associated with a higher rate of toxicity. And again eventually for those uh for those patients having a low grade of overall toxicity also the possibility of discussing the outpatient administration of the product could be also of of importance in h in this in this setting because of course we need al always to consider how to allocate these patients in the transplant center rather than the hematology and we I will talk a little bit about the importance of the communication between the referral center and the um qualified center for carti infusion which is of extreme important especially for the management of the early early toxicity and complication. Uh next next slide please which is on next one on monted cell lymphoma. Uh so for patients with mantal cell lymphoma uh uh of course the prognosis is uh very very different according to the line of treatment and also according to the h different possibility of being treated with molecular marker especially for those patients with severe with the TP53 arboring TP TP53 mutation or H in which of course the prognosis is extremely um impacted by uh the bi biology of of the disease. So of course the progression pre- survival and the main outcome for those patients relapse refractory change a lot according to the natural natural history and the the line of treatment. H so in uh the early referral especially for patients receiving um carti for relapse the refractory mountains and lymphoma is very very important because of course for in case of first relapse especially for those patients with the TP53 or blastoid or pleomorphic morphology those with a high risk feature before starting the second line which is most commonly with BTK inhibitors should be already considered for an early refer referral for for Carti. And this is really really very important because doing that uh patients with an early within an early referral looking at the early identification under the second line treatment within brutin but then can help in uh proceed with uh the the treatment in case of stable disease of progressive disease.
So already proceed with the carti referring referring the patient to the carti center or in case of partial response or complete response um proceed with a careful monthly monitoring in order to assess early sign of disease relapse in case of need of uh of course starting a treatment treatment then early in second line. not starting in thinking at the possibility of allocating the patient to uh the um treatment with carti when the patient is already relapsing after after the second line but try to shorten this time in order to allow the treatment with carti in the most um quick time also because of course the aggressivity of the disease and the biological ical biology of the disease when it it is resistant and highly highly aggressive is is very important. Uh so there are different main factor showing regarding mult lymphoma treated with carti from the real world evidence.
So namely patients with the one or two lines of prior therapy had a higher risk of CRS compared with those receiving cart after due to the burden of imunosuppression that is associated with the level of uh treatment progression free survival and uh relapse improved in patients with prior auto stem cell transplantation. And um it is important to consider also that the benefit of prior exposure to bendastin has been associated also with a reduced risk of severe toxicity namely icons and increased risk of trombocytoenia. So again it is important to consider which could be in we the place of cart in the algorithm of uh um the treatment for for those patients for also for uh conceiving the appropriate therapy and the appropriate bridging therapy until the carti is is achieved. Uh so uh it is um really really important to consider and we within the CTIWP recently early this year we reported a um a study on the physibility of um Braosell in patients receiving Braosell as second as third line therapy in patients older than 70 years old clearly showing how this treatment is also feasible in the population of patients older than um 70 with also some coorbidities. So what about the data uh from the real world data and the clinical trial? Again, very good rate of progression, free survival and overall survival, mainly demonstrated by the axis, the the the Zuma the Zuma 2 and of course real world data included also patient who were not eligible for the Zuma 2, mainly those having BTK naive or who received other bridging therapy. So again the real world data in this setting are very important to clearly demonstrate the feasibility of those patients also outside the the clinical trial. However, when we consider uh um how to allocate our patient with the different possibility and the different type of treatment that we have because nowadays we have a lot of product already available in the in the market and also in the different in the different lines lines of therapy. Of course for major concern remain for patient older in age patients for whom we may have safety concern and also the comorbidity of the impact of the coorbidity especially for patients experiencing a relapse in which of course the bargain of the pre-treatment is very very important and impacting in the tolerance of the different new product and of course I can discuss about the picture for Europe that is already a lot uh uh challenging for us the logistical challenges that we face in our uh in our activity is is very very important. Uh so one uh one one important um paper that work that we have been done uh doing with EBMT was to analyze the rate of utilization of cell therapy uh um to correlate with the e economical and demographic demographic factor. And this has been an exercise to correlate the treatment rate with the economic and demographic factor which may impact in the patient the patient history. So what has been clearly impacting in this looking at this study and it is here reported in this in this three picture that the proportion of patients that with an indication for allergenic orus transplantation uh was constant according to the um h groet income for the main European countries However, the h allocation for carti was lower and this is because being having this new treatment, the possibility and the resources allocated for putting the patient in the right uh uh time for receiving the treatment is less uh less impacting. So it is important as a community to increase the awareness and the understanding of carti therapy to expand the resources and the capacity to deliver this the the properly the cell and of course to develop sustainable and innovative finance financing approach uh to manage the cost and the cost of the treatment and the cost of uh uh the therapy the therapy and the entire management ment itself. So we within the BMT we have been working on the criteria for defining the main characteristics for the eligibility of carti because of course there are some uh condition for which the patient is h eligible for carti but there are different factor that interplay between the um true indication according to the criteria but the the real physibility. So uh first of all talking about non nonclinical factor the referral model is something very very important to be considered and uh to be really taken into consideration for the different patient who are eligible for carti but are not receiving uh the carti in time uh because of not a proper early identification. ation or referral and we as Europe we consider that approximately in Europe 30% of the patients that are in need of carti would not benefit of the treatment at the end of their h treatment journey. So the systematic discussion among the referral treating center and the qualified treatment center is very very important and the careful evaluation of all the potential patient is of a clear um interest in order to allow the proper discussion for each for each patient.
Once the eligibility assessment is shared, then the qualified treatment center can decide and should be in considered in the complex CAT evaluation to to assess the final fitness and then indicate the possibility of proceeding proceeding with the with the treatment.
And of course the qualified treatment center should perform the initial assessment very early in order to shorten the brain to vein interval which is has been which has been reported to be associated with better clinical clinical outcomes. And one example that has been adopted in some center in some countries like in France is the apheresis. the Apheresis the the centralized afferesis center and this has been also part of the new re-evaluation of the fact and JC standard which has been delivered in October 2024 and for the first time are joint between the fact so US and and Europe clearly showing how um a single collection uh which include The apheresis, maro and other tissue source is considered and it is possible for center want to proceed with the accredititation to uh um propose a standalone accreditation from for immunactor cell centers which is quite new. of course challenging because it could be of um risky especially for the management of the toxicity not having the resources and the infrastructure of doing also the allergenic stem cell transplantation.
But it is important to be to consider this as one possible opportunity. And uh talking about the qualif the decentralized affair center. This is something that has been adopted in some country especially in France in which it is the the the referral center could eventually be responsible of also of the affairs to be delivered then for the product the manufacturing and then eventually the patients come back to the qualified center later on. So uh talking about the the clinical factor there are different important uh factor that should be considered related to the fitness of the patients and then the disease related factor. So talking about the h patient's fitness age is of course one of the most important factor that is associated with the different outcomes also in the setting of stem cell transplantation and several different reports have clearly demonstrated how carti remain affecting and safe in older adults including those patients older than 80 years old across the real world cohort. I have briefly mentioned about our publication in the setting also of patients older than 80. And this would be also of interest for patients with multiple myoma in which of course the age and the different possibility of treatment is becoming more and more in the advanced age of their of their um treatment journey. Multiple multic-enter and registry studies confirm comparable outcomes in older patients when treated with antiCD19 carti and of course as we are all used to do with in the transplant setting a comprehensive geriatric assessment helping identify older patients who may benefit of this uh this kind of treatment. It is important to consider that CRS and icons risk is product dependent. We have more nowadays more evidence of higher toxicity profile of Axisel versus the other product. And eventually for patients in advantage is the risk the choosing the product associated with the lower risk of toxicity is probably suitable and age alone should not be a criterion for excluding patients from Cartier referral. uh then the geriatric assessment can help in identifying and properly select the uh main product for for the patient. And this was the paper I was I was referring before on patients older than 70 years of age treated with braus cell for relaps relapsing refractory multis cell lymphoma with of course um very high grade of CRS or grade and icons but again the proportion of patients experiencing more than grade three was approximately 10% % and a very very effective overall survival and the progression res survival reaching 60% in um in those uh in those patients and again in a subgroup of patients treated being older than 75 there was no difference in term of outcome. So the most important factor is not the age per se while the frailty of the patient and the and the performance status. So the functional status and not the chronological age should be considered as the main factor for uh uh choosing one treatment another one. What about the CNS involvement? because patient with CNS involvement patients can be uh um treated uh both for the present of CNS involvement primary or secondary in a second relapse. So originally those patients were excluded from from the trial. However, uh the the data from the real world and again this is the importance of having this kind of witness and reports h patients with the CNS involvement can be safely treated with CARTT at the experience center showing um level of neurotoxicity comparable to those seen in the systemic lymphoma population. This has been a publication of last year by the group of the lymphoma working party in Emosphere in a court of over 250 patients treated with the primary or secondary CNS involvement clearly confirming how this uh this treatment can be also feasible in this in this setting. So again we do not preclude the possibility of this kind of treatment in patient with uh disease um involvement of of CNS. Of course, the management of the toxicity should be very very tailored with um EG baseline and of course h preemptive treatment with anti- um Caesar in order to prevent the risk of severe complication which have been indeed reported after carti like grade five icons or cerebral cerebral edema. Uh what about active infection? Uh although clinical trial of course excluded patients with active or chronic infection uh real world data demonstrated that um infection should not automatically preclude the possibility of carti referral. Uh so again it is uh important to proceed with a an early referral in order to uh um establish an individualized management plan for the active infection and then align the timing the appropriate timing when the infection is cleared. uh of course other serositivity for HIV epatitis BC is not a control indication with the CI the CIBMTR and the BMT. We are working on identifying the outcome evaluating the outcome of patients treated for lymphoma with carti having an HIV infection. We are at the data at the stage of the data collection.
However, it seems to be not an exclusion criteria. So those patients who are of course more fragile are also um uh benefit may also benefit of this uh this kind of of treatment. And it is really really important to assess a sort of infection prevention at the at the time of carti infusion as patients receiving carti are indeed immuno compromised and very often associated with a high burden of of disease. So it is important to consider that the assessment with the score that we have such as the amatoto toxicity score are important to identify those patients being at risk of IAT. So the long immune factor cell associated amoto toxicity and who can eventually benefit of pro antibacterial or antifungal prophylaxis in uh in their in their journey. So the car emotox score is a validated tool for predicting the toxicity before carti using the number of nitril count the plantoglobin cp and feritin. So very easy tool which are commonly done and performed during the patient uh patient referral and then identify those who may benefit for instance of early GTSF administration or antifungal or antibacterial prophylaxis.
So again this is the assessment of the infection risk before uh carti is of extreme importance uh to identify the again the possible the possible patients who are at risk of severe severe complication and uh just to conclude the main disease disease related factor as uh this um let me see why this slide are not going uh as not only the patient characteristic but also uh uh I don't know why the slider are not moving let me see no it's not moving if you going can go to the next exactly uh thank you uh so the disease related factor which are of of course associated with several important um impact in in the setting.
Not the previous one.
>> Wait, the the previous one.
Okay, this one um uh so associated with um with the important regarding the most important biomarker. So uh there is a different sect um different factor that can be associated with the response and also with the incidence of adverse event. We have discussed about the emoto toxicity but also there are factor associated with the T- cell fitness which in which the of course the tumor burden and the inflammation which is associated the systemic inflammation uh to assess and to reduce of course in h to to to reduce the risk of uh complication. Then the less imunosuppressive to more micro micro environment and we have seen how the different kind of treatment that we are using also to manage the HLH after carti or the other inflammatory complication can be also associated with with this this kind of response. and of course also the event that occur after the the infusion such as uh the CRS and the other neurological event. So this is uh the disease related factor are very very important and if you can go to with the with the next slide please. Yes it is okay. So this is the the data showing the benefit of cartine in second line for both axis cell and and lizo cell and clearly demonstrating how in those those patient the the tumor pardon the level of the tumor bard. So achieving a um stable disease before the Garti infusion was associated with of course a better better outcome after after Garti. So of course uh the this may switch the place of the auto stem cell transplantation in a later stage of the disease. But of course it is very very important because it allow uh to get um an overall response rate uh reaching 80% in the different in the different setting and um what it's very very important to consider nowadays this is something that we can h do with our patient in h during the first line journey of patients with high risk disease. Um proceeding with an interim evaluation of the disease response and in case of stable disease of progressive disease then starting considering those patients eventually bene eventually at indication for for the carti. So really the ability of the referral physician to identify the eligible patients in a timely manner is really critical for the optimal carti cell therapy usage. And of course, these are data from a single center showing how uh the the the outcome of patients receiving an easier access to carti had a better survival compared with those at the referring center center dislocated.
So clearly demonstrated how the um collaboration between the different center and the indication with the multidisiplinary team or national or regional discussion uh are very of and early referral of patients are extremely important to put the carti treatment in the best moment and the best time for in the algorithm of of the patient um of the patient selection. So just to conclude while cartisel therapy has a curative potential still barrier resist to the access of this treatment and equitable delivery. um best practice across different countries have been identified to overcoming the this barrier and of course it is important to consider the perspective of the stakeholder in order to different country have their own system which should be of course sustainable because we had a huge number of patients with different disease indication who may benefit of carti So of course the the reduction in cost should be uh done as as a really really commu a community and the ensuring the access to guarantee for all leadable patients of course require an holistic approach integrating the patients related consideration with the appropriate investment.
And with that, I conclude thanking all my colleagues from the cellular therapy and the immunobiology working party of the BNT, the go-kart coalition, all patients and families and all my colleagues in S Rafael and all of you for your attention. I'm happy to take a question. Thank you.
>> Uh thank you, Professor Analysis for that excellent overview and sharing a global perspective on cartisel therapy.
Uh so we have a panel discussion uh following this so maybe some of the questions get uh answered in the panel discussion. Uh so uh it gives me a great pleasure to introduce our esteemed moderator for the session Dr. Vipilshi.
Dr. Vipple is a senior consultant in the department ofoncology at Rajiv Gandhi Cancer Institute and Research Center Delhi. We are also privileged to have an exceptional panel of national and international experts.
So it is indeed my pleasure to introduce our panel for the evening. Professor Analysisa, Dr. Ibrahim Al- Labani from Sultan Kabush University Hospital, Oman.
Dr. Asuk Sebastian from Bjil Cancer Institute, Oman. Dr. Padmma Loki, consultant at Apollo Cancer Institute, Hyderabad. Professor Udai Kalakarani from CMC Well, Dr. Nitin Sud from Maidanta Hospital Gurram. Dr. Vishwanat from Apollo Hospital Bangalore. Dr. Punit Jane from Apollo Hospital Navi Mumbai and Dr. Nira Gupta head CDM at Immunil. So without any further delay, may I invite Dr. Vipul to moderate the panel discussion on expanding access of cardelkin lymphoma. Thank you sir.
>> Hi. Hello everyone. Good evening. Am I heard?
>> Yes sir.
>> Okay. Uh first of all I would like to thank Dr. Hucheri as always. Um I'm great pleasure listening to you. Um u I would like to thank Dr. Pankage Malitraas for giving me the opportunity to moderate this session and for excellent overview of development of car in India and all the esteemed panelists.
I'll just be asking questions u pertaining to each panelist and would also want opinion of Dr. Vuji and Dr. Malotra like where they can add in to whichever questions.
Can you move the slide please?
So the first question is to my dear friend Punit. Uh how has the treatment paradigm of relapse refract evolved especially after Carti cells from the conventional that we used to use while studying?
>> Yeah. Uh so uh thank you for this uh uh question. I think uh Dr. Professor Analisa has summed it up so beautifully well that maybe I don't have to answer anything clearly uh you know those patients who are refractory and uh you know some of them uh relapse within 12 months they really don't and many of them in fact are transplant ineligible early almost 50% as per the information that uh professor had shown uh clearly Karti has made a difference you know and it it and it's even useful uh as per the CIBMTR data early on in you know after uh first to second line uh refraciness rather than pushing it lower down the the treatment paradigm. So uh with the Zuma 7, Zuma 5, the transform trials uh clearly carti cell is right up there and you know with uh the availability of Indian cartis uh in the form of immunact product and imunal product we we we can uh offer this early on in the therapy especially refractory or those patients who are uh relapsing within 12 months of their therapy.
Thank you Punit. Uh Dr. Rjeri, would you want to add something to it ma'am?
>> Yes, thank you Vul and Punit. I I agree.
I think that um this the the results and the confidence that we have now with the use of Karti clearly demonstrate how this treatment are feasible and should be proposed to our patient. Of course the the place of uh other treatment as we were discussing about the atlogus with all the complication that are associated with the high level of chemotherapy and also the risk of um secondary myislastic or acute leukemia associated with this kind of treatment should be considered. So having an ear early referral to this to this um to to and the benefit of this treatment clearly uh h open a new perspective to to the patient.
>> Okay. Thank you ma'am. Uh can we go to the next question please? So this is to Dr. Padmaaja. Uh which initial subtypes are currently deriving the maximum benefit from cartisel therapy? I mean we are most used to DLBCL but which other subgroups would you suggest?
The max benefit most of times we are using you know bus lymphoma patient very well got less of inflammation it's an indolent disease always be counel somebody with a follicular lymphoma you know that they would do well and the side effects complications are less so it feels nicer to treat a follicular lymphoma um in terms of complications are much less but the the commonest being DLBCL where we would start counseling mental celloma I'm yet to consider somebody for a carti for mental cell lymphoma so the follicular and DLBCL seems to be the the biggest chunk and there is a lot of immediate need in DLBCL's compared to follicular where you're talking to the patient that you would benefit from carti and there is a time gap where the patient can prepare for compared to the other um you know lymphoma the high grade lymphoma yeah a large cell visa lymphas and I've used in triple head double head of DLPs >> okay thank you very much >> but certainly in the last um Dr. analysis showed the follicular ly informal response rates whatever the card you use between 80% to 90% which seems very promising in contrast to the DLBCL where about 50 to 60%. Yeah, thank you.
>> Yeah, thank you very much. Uh Dr. Pankash Malatra, would you want to add sir anything to this?
No, no, I totally agree with uh uh prettyity what she has said that uh the immediate need is in diffused large bell lymphoma for follicular lymphoma being uh uh indolent type most of the time. So you'll have time but obviously this is useful. We have used in mental cell lymphoma u uh but uh the you know patient relapsed at one year and uh did not do well. one year he was uh you know remained all right. So I I think these are the three main indications but uh you know when we talk of diffuse large B cell lymphoma now there are uh you know at least 10 more varieties of large cell lymphoma so probably all CD20 positive you can possibly use so then thank you this question specifically directed to you what are the current EBMT recommendations for use of cart in relapse refractory >> thank you vibul So as I was mentioning uh following the main indication as uh uh the approval of the product nowadays the early use of carti after of course the relapsing earlier those early relapsing after the first line is clearly a benefit especially in term of uh overall response especially also in patients with aggressive double it or triple it disease. And I would also mentioning um just a recent publication that is being accepted and delivered yesterday because we have currently the European hematology association meeting in Stockholm on the impact of um the fertility recovery of after carti. This was the paper has been published in Lancet clinical medicine which is a Lancet journal. Uh and we proceed with a survey across the different center and we were able to identify more than 20 pregnancies after after 30 and especially those occurring in female patient. Half of them were spontaneous. So even these we believe as EBNT and as a community that these are really important message to deliver for the patients also in the counseling because those patients that can be cured and then recover also with the fertility in terms of uh spontaneous pregnancy. it is of extreme importance and as I was mentioning also for the other indication such as the autoimmune disease. So early referral and again reducing the uh the brain to vein uh period and discussing between the referral center and the qualified transplant center for the appropriate treatment and the appropriate bridging is extremely important to achieve a successful outcomes.
>> Thank you. Uh next question please.
Uh so this is to again my dear friend Gud. Uh which patients are idle candidate for cartisel therapy? I think I mean we discussed this in previous things. So you can just summarize it quickly please.
>> I think uh this was already covered in the previous uh questions as well. I mean broadly from our experience if you have lesser disease burden and you are on you know you are likely to have a better response. So we would always try to give uh some form of uh chemotherapy trying to get a response prior to moving to carti and lesser the disease burden before carti. I think in our experience u those are the patients who have had uh reasonably good outcomes. Uh but yeah happy to learn from uh Dr. Agiri and uh Tamalotra as well.
>> Dr. >> Yes. Thank you. So yes, the ideal this is the ideal candidate is again something that should be really really considered according to the uh felty scale the level of the disease burden because we clearly have evidence that the high disease is impacting with both toxicity and um and also overall outcome. So h assessing the appropriate bridging for for those patients is is very important in order to reduce uh the risk of uh important uh important toxicity. So I believe that patients should not disch this discouraged for this treatment according to uh the disease characteristic. But of course progressive disease refractory with high tumor burden and high inflammation would need uh um bridging therapy before appropriate bridging therapy to achieve a better disease control before before carti.
>> Thank you ma'am. Uh can we go to the next question please?
So this is to Dr. Ashuk Sebastian. How do you decide between transplant versus carti cells in relapse disease? I mean I guess this pertains to DLBCL mostly. We have discussed it earlier. So if you can just summarize it.
>> Hi good evening. Uh am I audible?
>> Yeah you are.
>> Thank you. Yeah so thank you so much uh uh professor for that uh very extensive uh talk. Uh so this is something that we have always struggled with to decide uh between transplant and carti. Most commonly the deciding factor is the fitness of the patient. Uh if the patient is uh borderline fit or if the patient is frail we tend to prefer carti because we see that that's more tolerable in such patients. Um but also uh I usually choose to send for cartisel over uh auto transplant in patients who have an earlier relapse. So if they have if their primary refractory or relapses happen within uh the first 12 months I would uh suggest the patient go for cartisel therapy. Uh and of course the high-risk um uh patients as well because the last patient I sent for carti was a double lymphoma. So those sort of patients uh I feel don't really do as well on um auto transplant as compared to uh cartis cell therapy. So I'd say the three things that we can of course the final thing is is actually cost because there are places um so I'm currently practicing in Oman but I'm from India and there are places in India where u auto transplants are still much cheaper than cartisel although the gap is closing. Uh so logistics comes probably fourth. So the relapse patterns uh the sensitivity the response to uh initial response to chemo uh the fitness of the patient and of course the logistics are the four things that I'd consider before deciding between these two.
>> Thank you very much and uh Dr. Pankage Malifas you want to add something?
>> Uh no no I totally agree with uh uh Dr. Sh. So there are a lot of factors and these days we talk about T- cell uh uh health uh both when you're using CT cell therapy as well as when you're using bicep specifics. So uh so if the t- cell health is good then most of these patients would do well over a period of time. So which basically means that if the patients have received u fewer chemotherapies uh then obviously their T- cell health is better and these patients are going to do uh good uh in in fact I have a one theoretical question to uh uh Dr. Analysis uh you know has anybody we used to do you know a tandem transplant in some of those patients where we feel that the disease was high risk. So has anybody tried doing an auto followed by a cart cell therapy in any of these situations uh uh you know in relapse retractory lymphas >> so um thank you for for the question Dr. Pankai. So receiving a carti after a relapse of auto.
>> No no no. So like we do used to do tandem transplant. So somebody receives an auto followed by a carti cell therapy.
>> Ah so thank you. Actually this is nowadays. So the tandem autocarti.
>> Yeah.
>> Uh so this has been reported by few case report. One recent case lion has been reported by the French group from the University of Bordeaux I believe but it is not yet published has been reported as abstract. I found but I can give you my personal opinion of course. I found it very interesting. But I believe that the burden of the also the the cative potential of the out and the carti alone would not um need to put together as an atandm also because of the risk of toxicity for patients undergoing an out and then the alastic phase as well the risk of of course severe CS in case of sepsis. But this is my personal opinion. Personally as a clinician I have not experienced in this because of course we have to follow the national indications. So we can never combine this kind of we have not this kind of freedom but I found this case report very interesting uh very interesting also.
>> Right. Thank you. Thank you.
>> Uh thank you. I'm just going one question forward from Dr. Malikra. Uh do you see any space of carti followed by alo just likel for very very high risk patients or >> alo after ki >> inflammation not not of lups just for >> no consolidation do you mean as consolidation but this has been discussed a lot for patients with bll for patients with nic lymphoma I think not only the potential curative treatment of carti but also the the farther option that they can have with the use of by specific to not justify consolidative approach with uh with the uh with the with the transplant the allergenic stem cell transplantation. I would be more conscious in monitoring the patients with early of course time point in order to assess the proper treatment in a case of further further relapse.
>> Thank you. So the next question is how do you compare real world outcomes with pivotal uh trial data? This is to Dr. NRA.
>> Thank you so much Dr. Webbul. I'm really honored to be part of this esteemed panel over here. I'm representing immunal here and I'll talk about immune data and uh one in cell academy. So one in cell uh initially got developed uh at hospital de clinic Barcelona Spain and then uh post tech transfer it was further for Indian patients. Uh we we did the trial and we have our investigator Dr. Pankach uh Malhotras over here as well. So we did that trial and this is approved and relapse refractory uh NHL in India and also being developed for all cases. So if you look at uh there was um question uh that the baseline characteristics of the pivotal data if you look at the median age was 53 years ranging from 31 to 66.
uh the DL highgrade DLBC in the data were 33% patients and uh 33 were poly lymphoma 25% were indolent cases uh Dr. Pankage did mention about the publication in blood ICD for our data.
Imagine study that has happened. Uh we saw at 3 months the 83% of orr uh wherein 70% of the CR uh that was seen.
Uh the question is pertinent because the trial is a small number of patients usually done and how it reinforces the finding in real world that becomes very important. So um in Spain if you look at um more than 600 patients have been treated uh with vanimal and in India 100 plus patients have been treated uh with one himself and uh we the data was also uh presented in hematicon uh last year and uh we we saw the uh overall response rate of uh 73% uh in that data. So it is comparable to uh the other global carties. This is a global carti that we have in India as well. So uh the data is comparable. If you look at the safety profile as well um the CRS any grade CRS was 67% which is like up to 90% we see in the global cartis and grade three was just 4.2% while we see up to 26%. Ians of any grade was not seen at all in our data. So uh the data of uh kmmy is uh comparable to other global cardi which Dr. Anela also presented the data of uh global cardis. So thank you thank you for this question Dr. B. I'll hand over to Dr. Panka if and anything sir you want to add to it because you have witness in real world.
>> No no so what you have mentioned is uh exactly that what we experienced when we were doing the trial. uh so uh I I I think the results are the same we have used in the real world also and uh the experience is the same. Yeah. Thank you.
>> Thank you. This question is to Dr. Ibrahim. Uh given the aggressive biology of burkits lymphoma uh where do you place cartisel therapy exactly in the paradigm of buckets?
>> Uh thank you so much Dr. Vupon.
uh well uh carti in bottoform is biologically attractive uh but I think it's um clinically difficult I think the main uh challenge is what is the disease tempo u so many of these patients progress during peripheral you know during apheresis post apheresis during manufacturing or during bridging the adult published experience remains limited to um retrospective um uh studies and it should not be presented in the same confidence as duilis cell in form. My uh perspective is that cartisel is feasible um only in highly selected burket u b patients patients with control disease kinetics good performance status no uncontrolled subsets and where you have access to um rapid manufacturing or clinical trial pathway for cartis cell therapy. I can share uh for example recently we had one patient with burket lymphoma and favorable young guy um both to cycles of madorati has a residual disease but it was very limited um uh limited localized um disease. We had a chance to collect and manufacture. Uh we bridge him and then we went ahead and infusing.
um that was in midappril. So now we are mid um mid June we had the day 30 bet scan which is um he's in CMR. So that's very good you know um but I don't think that's applicable for all patients with bracket inform.
Now the other thing to make a comment on is the multi- antigen strategies such as CD19, CD22 approaches are particularly will be relevant for bracket lymphoma because of you know single antigen escape uh and relapse remain a concern for bracket lymphoma. Um so I think um durability uh remains a key unanswered question. uh although we see some uh activity uh for carti in bark control.
>> Thank you very much. So just to summarize you used it in your patient to achieve partial response right not complete response but it was >> yes very good very good partial response but he had residual disease post to situs of um >> and this was high-risisk buckets to start with >> uh high risk very bulky disease um at the start.
>> Okay thank you very much. Um just to go switch gears what is the role of cartisel in primary CNS lymphoma? We just had Dr. Vijay showing excellent outcomes in CNS involvement also. So this is to Dr. Vishonat his experiences with primary CN.
>> Thank you Dr. Vipul and thank you immunal therapeutics for this opportunity. It was a wonderful talk by Dr. analysis and she did mention about the proof of principle and primary refractory primary CNS lymphoma that uh it can be done and we also have data from the French study as well as of a small number of patients of 27 as well as a meta analysis of 38 studies. So there is some data to say that it can be safely done in patients with primary refractory primary CNS lymphoma. So our own experience is quite encouraging. We had a 50-year-old uh woman who had relapsed primary CNS lymphoma initially treated with matrix and then she was not willing for transplant and then we put her on maintenance with the caliperinib rettoximab and lenolumad and sub subsequently she said okay I'll go in for stem cell but then the stem cell collection was inadequate and then she had radiation and then she had another round of chemotherapy salvage chemotherapy with rice so it was multiply pre-treated primary senus lymphoma And then that's when uh there was disease progression and then u you know there was some response with the salvage chemo and then we decided to go ahead with cartisel therapy. In fact she sailed through this cartisel therapy.
There was no major Ians no CRS and in fact as we are talking we just had one MR which was done uh probably this is a sixth month MRA and she continues to be in complete response. So uh this is my experience and uh you know it was very encouraging uh to have this one patient so we can do more for relapsed primary sinus lymphoma.
>> Thank you. So Dr. you would want to add some >> Oh sorry I confirm what um Dr. Vishanat was was saying meaning that it is feasible of course you have to consider and to manage the appropriate prophylax prophylaxis and of course early eg eventually but it seems to be feasible also in our experience we treated some patient and we had no different toxicity rather than the others >> and just to add I think the FDA has removed the exclusion criteria for the active cell recently.
>> So patients with primary sus lymphoma who are lapse refractory can be included >> as well as well with the with lis cell >> lis cell. Thank you.
>> Thank you very much. So the next question so this is to Dr. Nitin Sut. Uh how promising are combinations of tarti with biopecific antibodies or checkpoint inhibitors? Um I guess biopacific is too expensive here. So maybe checkpoint inhibitors.
>> Yeah. Well uh biologically very exciting but obviously they are still investigational. Um I think um I mean you know we've seen that carti is an excellent treatment option and many patients respond to it but there are some people who who relapse and who don't respond. So uh the antigen escape and the carti cell exhaustion being one of the primary biological reasons for that to happen. So if we can reinvigorate or or reexite the the carti cells then that'll be a uh that will be theoretically a good thing to do. So uh and it's theoretically possible to do that with checkpoint inhibitors especially pemmorismab and neolumab and we have access to both these drugs in this country. Uh I'm I mean I'm not promoting doing that but I'm saying it's an exciting investigational area. So yeah, very exciting. The bispecific antibodies although again very expensive have a complimentary way of working. So they can recruit uh the endogenous D cells as well as carti carti cells can uh and they're offtheshelf products. So they're very exciting to um consolidate treatment options or consolidate carti effect. uh the the real question is whether you do the bicep specific antibodies followed by carti or the other way around or in combination and uh these will be the questions that we need to answer in the coming times >> and if you use both these strategies as consolidation not post relapse which is CD9 positive how many months do you propose for each >> I don't know I mean I I think that's just far too down the uncharted territory I I really don't have answers to those questions.
>> So, Dr. Roger, can you um please >> Yes, I I agree. I agree that the place of uh uh the combination between the B specific and carti is very very challenging also because the physibility and efficacy of specific is clearly very very exciting. So I think we need some time to understand what is the appropriate place before or or after and this is also according to the a new indication of when the approval of the B specific in ear line would be deliverable but for the for the time being I think that the earlier place of carti is essential and of great great benefit >> and if you're using bicep specific as a consolidation strategy postcard for very high-risisk disease. How many cycles would you >> No, no, no. We are not using as in our clinical practice. We are not using as as consolidation uh strategy.
>> Okay. Thank you very much. So the next question >> uh people I would say that you have a good experience of using carti. So what is your experience? You can also share and I think you are involved in the clinical trials also. So you can share your experience. You are only asking questions.
>> Um so not even in Seattle we used to use any of these strategies as consolidation unless it was a part of trial. We had a trial in Seattle where we used antiped postcard as consolidation strategy. It was also inup but other than that I don't know of any consolidation strategy. uh for salvage if it was CD90 positive relapse then we used uh PD1 sometimes thinking that the T- cells are exhausted but I never saw any good response to antiPD1 post relapse which is CD19 positive glitter map for bi specific of course we used to use post relapse and we had good responses as a bridge and then we used to bridge it to an so I guess uh Dr. I never saw any good responses to antip post relapse.
Did you ever find any good responses if they were CD19 positive?
>> No, not really. I don't think I I I mean once they relapse it is more the strategy we we can again allocate to the use of bi specific and so on but not really a substantial response with the anti antiPD1 >> and if you're using bicep specific as a salvage post relapse of course >> do you always follow it up with an allergenic transplant or just six cycles and leave it if it is in remission It depends. It depends according to the patient. In case of a patient, young patient with the um wheelingness, but we do not propose the allergenic transplant after achieving a remission of the six cycle of bacific >> and you recommend six that's what we used to do in Seattle. So I don't know six.
We do not proceed with allergenic transplantation for lymphoma having relapsing after having achieved the remission.
>> Thank you.
>> Um how challenging is the disease control? I mean this question is pertaining to bridging therapy. How challenging it is uh to control the disease while the cars are being manufactured now that the manufacturing time is reducing. This is to Dr. Ibrahim again.
>> Yes. Um so I think uh this is one of the most important real real world barriers.
Um you know manufacturing weight is not just um a logistical issue. Sometimes there's a lot of logistics um on the on the way to um shorten the time from brain to vein. But uh many of the times it's a biological selection pressure.
You know many patients with bulky disease, rapidly progressive disease, high LDH, they may deteriorate uh before infusion. And I think many of us uh or maybe all of us who worked in CARTT centers or currently work in CARTT centers would remember few patients who um were collected but they were not infused due to you know deterioration before the infusion time. And I think bridging therapy should be um you know uh I think it's not should not be kind of random and should aim at disease control without destroying the bone marrow reserve um and worsening risk of infection later on. uh so um I think strategies like radiation for localized symptomatic disease steroids based therapy chemotherapy although there is some data now on bendastin may you know affect the uh carti function post infusion uh and this we're talking all after apheresis now uh by specific therapies could be used um based on arguency and access um recent um you know meta analysis published in blood advances showed that also response to bridging therapy was associated with better post cart outcomes um maybe it's just a sign that those who respond actually have better disease overall compared to those who does notice who does not respond so I think um uh I want to emphasize on two points one is that bridging respon uh bridging response itself is prognostic Um but we should aim at having disease control without uh destroying the bone marrow reserve or worsening uh the patient condition with infections or something else until like the product is ready to infuse.
>> So Dr. Pankage Malik say you want to add something to this? No, I totally agree with what Pakar Ibrahim has said that uh and uh you know repeatedly we are uh uh saying the same thing that you know you need to preserve the you know immune uh system of the body or the T- cell exhaustion should not happen otherwise you know your these cellular therapies are not going to work. Thank you.
>> Next question.
Um so this is for Udai. Are there any biomarkers which appear very promising to predict the response?
>> I have to apologize but I I'm I'm very sorry because today I am on call and as I have mentioned to Dr. Na and two people I have to leave. I I am really sorry because I believe the discussion is very exciting but I have to leave because I have still some clinical work to do. Um sorry for interrupting and sorry for leave earlier but uh I mean combining in a daily work day is not is not so easy and again thank you and if you want to propose a question or clinical case discussion I would be really really happy to to do that and again really sorry for for uh disconnecting earlier.
Thank you.
>> It's okay. It's okay professor analysis.
Thank you so much for joining us. We understand we are actually you know over exceeding our time but uh uh yeah but thank you so much for joining and uh we will maybe have you again uh at sometime in future. Thank you.
>> My pleasure. My pleasure. Thank you. And sorry is really sorry. Bye-bye.
>> Thank you. Thank you. Bye.
>> Bye.
>> So sir we continue right. So we continue finish. Yeah, we can continue but we I think uh uh in the interest of time we should uh try to finish in next five minutes or so.
>> Okay. So Udai quickly any biomarkers which which you can broadly what we have learned is that you know the early response to treatment. So if you do a PET at one month and if you have complete metabolic response then you know that group of patients does very uh you know well in the long run. people who are not in complete remission uh post the carti that's a group which invariably people who have some partial response uh will end up with progression and we have seen that in all the clinical trial data from India as well as uh uh you know western cohorts so I think uh that's something which is uh that population which is which has a partial response to karti probably that's a point which is actionable for us yeah looking at prospective trials in that space.
>> Okay. Thank you. Sir, you want to add something to it?
>> Panka, you want to add something to it?
What would they say?
>> No, people are looking at different uh kind of a biomarkers including you know looking at uh the V cell depletion by cytometer. We also have been doing that but uh doesn't uh you know very well correlate even if there is a B cell depletion some patients do relapse. So a PET at 1 month is a good marker uh to you know which can give you uh some idea although there are patients who still relapse after some period of time but there is lot of research you know which is going on to find out a good bow.
As you say, V10 never found very good correlation between BClasia and long-term dramation for lymphoma. Just like ALL, for AL is very important. I guess for lymphoma it's not that important. I mean the persistence of the C. I don't think so much of persistence is required for a lymphoma as compared to ELN. in the proliferation makes more difference you know higher peak values in the first one but that's where >> so I I would just add more than PET scan it would be circulating cell DNA which we used to do unfortunately we don't have it here but that is even more prognostic than a one month PET scan post uh >> yes >> yeah so next question is to Dr. NRA do you think beyond response rates durability and quality of life is equally important? I mean I guess it's the most important thing. So let's hear your >> Thank you. Thank you so much Dr. once again and the same Dr. Ibrahim also touched upon uh the durability of the response is very very important once the patients achieve the response how long they sustain the response that becomes very important. So if we look at the van cell data uh again the paper that Dr. Pangasa showed that showed that 42% of the patients they maintained the response uh till uh one year of time trip because that that was the cut off that time and out of that 38% patients were in CR. So this is something really appreciable to look at the durability of the response with van himself. Uh with the global data in Spain uh it is uh 39% at 3 years uh the sustainability of the response that was seen. uh having said that these patients they really need uh a better quality of life and uh we have seen in our cell data that all parameters of EQ5s for uh the routine care self-care all parameters pain anxiety depression mobility uh there was early uh sustainable and significant response that was maintained uh till the data cut off of 12 months So uh this both the things for these ailing patient becomes very important the durability of the response as well as maintaining the quality of life. Uh thank you Dr. Dr. Pa sir if you want to add anything please.
Thank you.
>> No no no I agree what whatever you said.
Obviously patients who are in remission they their quality of life is excellent and this is one time kind of a therapy and uh uh uh in fact most of the patients they do not uh develop any kind of a reaction and many times they keep on asking us why are you keeping us in the hospital you know postcard cell therapy and we say no no we need to monitor you for CRS and I can uh but uh uh you know the these rates are obviously very low and right Now in India we have not come to a situation where we can do these therapies on outpatient basis. So because of the risk of so many thing infections logistics and other things. So we still need to keep these patients in the hospital and monitor them for at least uh you know 10 to 14 days uh a minimum. Uh this is what is our practice uh at PGI. I don't know about the practice at the center but uh uh I think till the time we develop more experience only then we can uh consider these therapies on outpatient basis but their quality of life is most of the time is excellent for these patient especially those patients who have a low risk uh low level low burden of disease.
Thank you.
>> Thank you. Um so this is to Dr. Padmaaja. Um I guess this we discussed extensively regarding double it and triple it. Uh is there a role of carti? I mean the clear answer is definitely yes but I would like to hear your viewpoint. Uh can you go to the previous question please? I I mean Dr. Padma please.
>> Yeah I think we have discussed extensively. I've had one of uh one triple hit lymphoma patient who is primary chemactory after die epoch.
Couple of questions I had. This patient had a systemic disease and he had resolution of all the nodes apart from the the large primary source which is on the mandible which is very much visible.
Um it's almost refractory no touch with the two cycles of di so the next question is are we going straight to trans you know carti are we doing a local radiotherapy is it's a localized disease are we bridging with a bicep specific before you go for a car.
So as you start thinking about multiple opinions come um and certainly a bridging is a big option you know I've used auimab uh the biggest question is you only have in India sometimes your car is available within 2 3 weeks um so I felt using radiation you may have a necrosis you don't want to compromise the carti outcome and the second thing should we use by specific to get them into remission as it's a chemr but do I want to exhaust the tea cells when the bridging time is only 2 3 weeks you're going to get the car production done and I want to use a bicep specific this patient is going to be very bad one so I may achieve only a PR and I want to spare this by specific for a postcar consolidation perhaps so it's a kind of sequencing and the the thoughts about it so this patient I have had uh I've not used by specific I've not used radiation I've held on to it given some oentoismab uh and got on to car and he had a good response. We're waiting for a day 28 but this is a very visible mass so it's gone down by 90%.
If he has got a residual disease, my options are I want to use by specifics after the car and the next thing is are you going to wait until day 90 scan or day 28 you have a residual do you want to go on for? So perhaps these are the questions I felt this is a very interesting thing a lot of us face that they go for another opinion people say why not use a by specifics until your car is available where you are using one dose of autismab and then you have one dose of 10 milligrams of kulfetamab and then you're ready for a car so you've not used effective dose you're just using every agent a bit of it so uh I I really appreciate people's thought on it this is how I have done I've not used any And I've used a car and I've kept the no radiation and I've kept a car uh I mean by specific for the option of consolidation thinking that this is going to be a very bad patient. He may she may have a residial disease and may have to use it. So yeah I would really appreciate punk or all of you to say what you would do in the real life. So, so there is some evidence uh to suggest that uh you know using radiation uh leads to a better card response uh and we have used in one of our patient uh uh but there are uh research papers published which says about that bicep specific definitely no before the carti and uh this is based on the experience uh because we are going to uh you know exhaust your T- cell population so But you have done uh excellent. So both these options are open. So giving obotism app giving some form of uh lowd do kind of a therapy. Uh and then proceeding towards the carti. Uh so so this is our experience. We have used radiation you know when there was only localized disease to one site and that patient right now is doing very well but it is you know day 30 or day 35 close to day 335 only. So as we develop our experience only then you know we can probably after a couple of years we will be sharing our experience uh what kind of a therapy is better pre uh cartis cell. Thank you.
>> So sir I I have a question. So of course everyone knows that radiation adds to the effect of cars. It also has epscopal effect because you give it at the localized site. It still probably works at other site at least creating the micro environment for car. My thing is for very very aggressive lymphoma only having localized disease left after cleaning and you use only radiation precares that it might progress at other side before you give CAR. So do you combine radiation with some systemic therapy or a calibr or just give radiation for a localized disease?
for a localized disease only radiation and not any form of therapy because again we our worry is actually about uh you know the exhaustion of T- cells so only radiation if it is only localized to one place >> but what if it comes up at some other place while while you're preparing >> yeah so that's what I said you know it is too preliminary you know we are that that is the reason you know we are sharing our experience and I'm not saying that you know we are right or uh You know so it is only once you share your experience uh over a period of time only then we would know some of the answer we would know after maybe few years.
>> Thank you sir. Um so I guess now the last question remaining for pun. Um has earlier intervention with tossi or steroids changed any outcomes and do you use it very early in your practice?
Yeah, I mean uh obviously there is always a debatable role about its use as a profileactic regimen but preemptively you know prolong grade one or early grade two we definitely use map and then you know if there is grade three we add steroids so definitely it reduces the the the severity of the CRS if if nothing else so it doesn't affect any carti cell expansion or something so these are my thoughts I mean you know they they they are mainly it's mainly used for prolonged grade one or mainly grade two uh uh uh CRS.
>> Thank you very much sir. you would want to add something >> uh for bio specifics when we are using I am uh you know based on our experience in myoma I can definitely say for Indian setup uh it's good idea to use toileisome uh and the reason for that is uh because of the patients fever many times in India we are not sure whether it is because of the infection or because of the CRS and then uh uh by default we start the patient from antibiotics first and if it is CRS then obviously you are using time. So but this is based on of our experience of using bicep specifics in myoma but here in Karti and whatever carti which we are using we have not used profiles withilismab and uh we just monitor these patients.
>> Thank you very much. I guess this was the last question right NRA.
Yes. So we want closing remark from sir.
It's all it takes.
>> Yeah. As sir presents as sir presents closing remarks. May I request all the faculty members to switch on your video so that we can have one picture of all the faculty together. Sorry sir. Over to you sir.
>> No no no it's it's okay. I think it's good idea to have first of all you know I would like to thank uh Dr. Shirinasa and Dr. Mira to organize this kind of a symposium.
uh uh on Karti and uh uh I I think this is very important because we all at our uh institutes we are developing experience. We have only you know very few patients and uh we need to come together and share the experience of real world experience. You know there are papers there are research papers but unless you develop your real world experience and share that uh we will not progress. So uh thank you so much uh Imunil for organizing uh this kind of a symposium and having an having an excellent uh uh uh you know experts of who did the panel discussion and shared their uh experience. uh we have discussed quite a bit about uh you know ki and uh obviously uh even if there are you know 3 hours four hours we can there are so many things to discuss about the carti we cannot finish in you know just in one and a half hours time we have already actually exceeded our time for half an hour uh but maybe you know some for some other time we can have some other aspect of karti and uh in future we can discuss about that so thank you again for inviting me and uh uh you know asking me to participate in this uh in this symposium. Thank you so much.
>> Okay. Thank you.
>> Yeah.
>> Thank you.
>> Thank you. Thank you very much. Thank you everyone. Uh with this we'll conclude the session and we really hope this discussions inspire further learning and collaboration. Thank you all. Have a wonderful evening.
>> Good night.
>> Thank you. Bye bye. Bye bye. Thank you.
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