Manali Kamdar, MD, on Rapid Oral Abstract Highlights: Three Emerging Trends in Lymphoma Care

At ASCO 2026, we just wrapped up a very informative rapid oral abstract session in lymphomas. It highlighted multiple trends that are emerging in the field of lymphomas. I would probably encapsulate it in three themes. The first theme was around frontline diffuse large B-cell lymphoma treatments with the goal of improving historic outcomes with rituximab and chemoimmunotherapy. So with that in mind, we had the OLYMPIA-3 study, which looked at odronextamab, which is a CD20 bispecific T-cell engager in combination with CHOP. The complete response rates are upwards of 80% so far. The progression-free survival at this follow-up also looks quite impressive. With regards to the other study that was presented in frontline diffuse large B-cell lymphoma, it incorporated golcadomide, which is a novel immunomodulator in combination with pola-R-CHP. Again, complete response rates were upwards of 85% agnostic of cell of origin. In both of these abstracts, I think one theme emerged was that the efficacy signal is looking very promising. Patients are progression-free, which is good at a follow-up that we have so far, which is limited. But the toxicity signals, I think, definitely need to be watched out for from the standpoint of Grade 3 and higher infections, for example, febrile neutropenia, 30% chance. So the big question is going to be around how do these studies span out in phase III randomized control trials, which are going to be, they’re actually enrolling as we speak because at the end of the day, we want to cure our patients but also give them minimal toxicity. So I think balancing it out is going to be a theme that’s going to eventually emerge with better programmatic prophylactic care of growth factor support, antibiotics, antivirals. The second theme that emerged at the session was building on the existing cellular therapy. So with autologous CAR T-cell therapy treatments, I think it’s revolutionized. It’s revolutionized outcomes in large B-cell lymphoma, follicular lymphoma, mantle cell and CLL. However, manufacturing delays preclude a lot of patients to get into CAR T on time. And so with that in mind, we had three and three to up to four abstract presentations. What really struck my fancy was the AZD Cell data, which was an allogeneic CD19 platform. It was tested in CAR-naive patients and interestingly demonstrated very high responses and durable ones in marginal zone lymphoma and CLL. In fact, there was no guidelines seen in patients with CLL. I thought that was very interesting. So looking forward to more from that team to see where AZD Cell takes us. The second was more around manufacturing capabilities and with that in mind, there was RevOU from China wherein this was a completely gene editing-free technology which could develop universal CARs. They only had four patients that had received them so far. None of them had received prior CARs. But the scalability was very impressive because one donor batch could actually produce 3000 doses. So I thought that was something that really was very intriguing. Love to see where this goes within the CAR spectrum. I think in vivo CARs was really something that we have all been looking at. We finally have a little more data. Again, few patients, but in vivo CARs where basically the idea is that the CARs generate in the body, it takes away the manufacturing time, takes away lymphodepletion, and so far the results look promising. They do need multiple doses of the CAR construct, but so far in mantle cell lymphoma and diffuse large B-cell lymphoma, these were the four patients that had got tested in. I thought the results look quite promising and then I think for for a long time T-cell lymphomas and continues to be an unmet need. CD5 CARs have often been fraught with fratricide and infections. So this abstract with CD5 CARs actually shows that there were responses. The follow-up is short. Majority of responders got taken to an allotransplant. However, the infectious risk continues. So the idea for the next generation here would be to figure out how quickly can we identify viruses, make sure we treat them, or maybe use this strategy as a bridge to an allo, as a bridge to an allo transplant. And then last but not the least, I think the third theme was around biology. I think we are beginning to know a lot more about diffuse large B-cell lymphoma. We already know that it is not one disease. It is actually divided into several different types based on the test that you do. So we have the Hans algorithm that divides it up into germinal center and non-germinal center. We have gene expression profiling dividing up into germinal center and ABC. We have molecular profiling dividing up into five different types. So I think based on the molecular profiling, there was a very interesting study of several 100 samples that looked at the DLB class and the C1 through five class to look at CNS risk, CNS relapses. And I think it was the key theme that emerged was patients who have an MCD or C5 phenotype of diffuse large B-cell lymphoma had a slightly higher chance of CNS relapses. The big question is how do we figure this out in clinical practice? How do we do this in real time and how do we how do we potentially incorporate novel agents for these patients who are at risk for CNS relapses? So that is something that was very intriguing and potentially quite actionable as soon as we have this ability to run through DLB class or C1 through C5 in our clinics. And last but not the least, we also got some more data around POLARIX with regards to the lymphoma archetypes. So the tumor environment called the LymphoMAP and this data basically showed that pola-R-CHP was better than R-CHOP for all the three subtypes. I think the big question is what do we do of so many different subtypes of diffuse large B-cell lymphoma? Should we run them in parallel? We have the LymphoMAP archetypes, we have the gene expression profiling, we have the molecular profiling. So it’s a good time to be in the field. I think a lot of things are happening simultaneously where we are building on better biological tools, but at the same time, we’re also improving on our therapeutics. So in a sense I thought it was a very insightful session and I really thank all the speakers.