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So, here I am today with uh Doctor Kamdar. We're going to be talking about, ask, 0, 2023 and the hot topics that everyone was talking about in lymphoma. Uh Doctor Kamdar, could you give us a little snapshot of your research interest and maybe a little bit about your career history today? Sure. Thank you very much. Um Pleasure to be on this podcast. My name's Manali Kamdar. I am an associate professor at the University of Colorado Cancer Center. Um I'm a hematologist oncologist by trade and I specialize in lymphomas and I primarily specialize in doing clinical trials focused on cellular therapies. So at this year's ask, oh, I think we had a lot of data. Um but some of the data is actually practice changing or has the potential to be practice changing. Um Since secular therapy so dear to me, maybe I will start off with some of the updates in secular therapy. So as we all know, carticel therapy targeting CD 19 has changed the outcomes and patient's with relapse refractory, diffuse large B cell lymphoma. Previously, patient's who uh could not achieve a remission after an autotransplant could not get to an autotransplant, the FDA approved carticel therapy, namely ACSI cell lysis L as well as T cell in the third line setting. And with the help of car T cell therapy, we were able to salvage nearly 40% of patient's who would have otherwise succumbed to their disease party worked post autotransplant. So it was intuitive to test it in the upfront setting in terms of bringing it forward. So thus was the birth of three randomized clinical trials. Uh namely Zuma seven testing, acsi cell versus standard of care, transform testing, license cell versus standard of care and Belinda testing, decisional occlusal versus standard of care. All of these three phase three pivotal studies were tested in patient's with high risk relapse, refractory, diffuse large B cell. Um former, not all relapses are created equal. We do know that patient's who are primary refractory, all have relapsed within the first year of receiving riTUXimab plus chemotherapy have an exceptionally poor outcome even with an autotransplant. So these studies were really tested and transplant eligible individuals. And the net is that two of these studies were positive, the primary and point of event free survival was met, it was statistically significant and superior with regards to access Ellen Lycelle as compared to standard of care. What was very, very promising and important to highlight at this year's ASCO meeting was the fact that there was now a follow up off the Zuma seven study and there is now emerged an overall survival benefit on the zoom A seven study crossover was not permitted on study, but it was permitted off protocol. So people on the standard of care arm who did progress were able to get access selloff protocol. So with that in place, it's actually really important to highlight that for this high risk relapse refractory subset of diffuse large B cell lymphoma patient's, it's really important to refer them to a cardi cell therapy center. Um It definitely establishes in my mind, the role of cardi cell therapy as a second line therapeutic option in patient's with primary refractory and relapse within a year, diffuse large B cell lymphoma. So that was the update with regards to Zuma seven and CD 19 directed cardi cell therapy and diffuse large B cell lymphoma. The second update came in the form of listen, Captain Jean Marilou. So this is also a CD 19 derived cardi cell therapy product. It differs from axis L in terms of its co stimulatory domain for one BB and license Celsi D 28 and access L. There are other subtle nuances as well, but that's prime it really the highlight. But listen, Captain Jean Marie Lusa was actually tested in the trans end CLL 004 study and relapse refractory chronic lymphocytic leukemia and small lymphocytic leukemia lymphoma patient's. Um and this was the primary analysis of the study extremely important to highlight that patient's actually did really well. The overall response rate was 43% and the CR and cr I was 18% it seems sobering. But remember it's by the IW CLL criteria, I think within CLL, we have clearly moved beyond the definition of IW CLL. We absolutely are aware that MRD is very prognostic and it's important to highlight that the MRD rate on the study was upwards of 50%. Um The grade three grade four toxicities were very manageable. Great. Three neurotoxicity was 18% at this point. Overall, I will say the duration of response is very promising at 35 months. So the big question is, will lysis l finally get its approval for patient's and the relapse refractory CLL study um in the relapse refractory CLL setting, I think um you know, once we get um some information from the regulatory bodies, we would be able to understand if this could be a potential third line option for patient's who fail a BTK inhibitor and a BCL two inhibitor. As we know right now, we have BTK inhibitors for patient's with CLL BCL, two inhibitors for patient's with CLL. But we certainly have a subset of patient's with hire a CLL who fail both of these agents. I think for that subset like Captain Jean might actually prove to be very, very useful. Besides of course, the non Covalin BTK inhibitors like Puerto brute Neb, which I'm hopeful will also receive approval. I think the third study that I'd like to focus on is um uh clearly uh potentially practice changing study. Uh This was the swab study swab 1826. It was presented by Alex Herrera and colleagues. I am part of the swab group as well. So we are very delighted um that on behalf of nearly 1000 patient's this patient, this study was presented. Uh This is a randomized study which um in patients with advanced stage, Hodgkin's lymphoma. Uh these patient's were not just adults but also the A buy a population. The children's group is also contributed significant amount of patient's um for this study. This was basically a study randomizing Brenda map plus A VD, which is the current standard of care for advanced stage. Hodgkin's lymphoma versus nivolumab plus A VD. And I think the net is that the progression free survival was the primary endpoint and at the one year mark, it was met. Um one year progression free survival was over 94%. On the other hand, it was in the eighties for a plus A VD impor. I want to highlight that even though there is no overall survival difference. Yet, the toxicity profile was very encouraging. There were no immune mediated toxicities of high concern on the nivolumab plus AIVD arm. They were all manageable neuropathy rate was significantly higher on the brentuximab arm, neutropenia was higher on the nivolumab plus AIVD, but it did not translate into febrile neutropenia. Um Overall, I think this has the potential to change primary therapy for advanced age hodgkin with the incorporation of PD one inhibitors to the chemotherapy backbone. Um So overall, I think these were probably uh key abstracts that come to mind. Besides, there were also a few others, for example, there was the follow up of the Lyme A study um just to quickly refresh the memory of our audience here, Lima study is a study in frontline mantle cell and former patient's uh so young transplant eligible patient's were taken to a transplant. And after transplant, they were randomized to either getting riTUXimab maintenance every two years, every two months for three years or placebo. And at the three or four year follow up that was presented a few years ago, it did show that not only was riTUXimab beneficial in making it improved progression free survival, but there was a distinct overall survival difference. What was really interesting about the seven year follow up of the Lyme A study that progression free survival uh continues to be superior on the riTUXimab arm. However, there is no longer an overall survival difference. Um It's very intriguing. It could either reflect the fact that people on the observation arm are progressing but may not be dying because of nor treatment options that are now available because of which may be, the overall survival benefit has gone away. But nonetheless, I think the bigger question now incl clinical practice is how much shall we truly push riTUXimab maintenance in a post autotransplant patient's, as we know, you know, most of them will tolerate it fine. But this discussion is very similar now to people with indolent lymphomas like follicular lymphoma where riTUXimab does cause a significant progression free survival difference but has not elicited an overall survival difference. So I think that discussion remains quite similar for mantle cell lymphoma. So for me, the net is that if someone is having neutropenia because of autoimmune neutropenia, secondary to riTUXimab is having lots of sinus infections, upper respiratory tract infections. Um as a result of the hypogamma global anemia, I'm probably not going to push riTUXimab for those patients' post autotransplant. Um considering that the overall survival differences now no longer there. Um So I think these were the key abstracts that uh certainly um took um you know, make, made me take notice at the most recent ask or 2023 meeting. Um I think in the next few um you know, months in the next following conferences. I think there is a lot of data with regards to cellular therapy, immune therapy, for example, by specific T cell engages targeting CD 20 like Keratoma Bluff. It um ab most inotuzumab, I think these are all going to be moved ahead um in the treatment algorithm in not just diffuse large B cell lymphoma but also in follicular lymphoma. So I think the therapy options exist, they are increasing. Our toolkit is continuously growing. I think we really have to figure out a way now to sequence better in patients with indolent lymphoma. And for our patient's with aggressive lymphoma, I think we really need to make sure we have our goal to cure everyone and I think that can only happen with a clinical trial in place. Um So with that, I'll come to the end of this podcast. Thank you very much for having me. Thank you so much, Doctor Counter for an amazing summary of lymphoma. Asked 2023. We're really grateful for your time and a snapshot of what sounds like amazing conference. Thank you. Thank you.