ICML 2025 | Key takeaways & trials from ICML in DLBCL, MCL, and FL: POLARGO, STARGLO, MorningSun & more

It was really a great meeting and there was a lot of advancements which were presented. I think the key ones were in relapsed/refractory DLBCL, but I’ll start with frontline DLBCL and I’ll maybe get going with the thought that bispecific antibodies have really made significant progress in both DLBCL as well as follicular lymphoma. And while they are approved in third line plus, they are making their way to second-line and also to frontline. So that’s the general theme. And I’ll get started with frontline DLBCL. So in frontline DLBCL, we participated in a study of glofitamab plus R-CHOP or glofitamab plus Pola-R-CHP, where glofitamab is introduced from cycle two. So first cycle could have been R-CHOP or Pola-R-CHP, and then glofitamab starts in cycle two with a ramp up. And at the end of treatment, the overall response rate and complete response rates were really high at 93 and 86% with glofitamab R-CHOP and 100% and 96% with glofitamab PolaR CHP. And importantly, most complete remissions were achieved in the first interim assessment. And in terms of durability, we have at 24 months, about 80% or so patients were progression-free. So I think that’s a very important study moving glofitamab to the frontline therapy. It was also good to know that the CRS rate was very low, only about 10 or 11% of patients had CRS and mostly all were grade one. Only a couple of patients had grade two, and there were no grade three, grade four CRS. And only two patients out of 80 received tocilizumab. So these are things which are commonly going through, you know, the minds of physicians and who are treating with bispecific antibodies, like, can you do this as an outpatient? And do you need to use tocilizumab? And, you know, this trial kind of showed us that maybe after debulking with one cycle of chemotherapy, when you introduce a bispecific antibody in cycle two, they have very high efficacy, durable responses, and low toxicity. There was another study which was presented in frontline DLBCL with glofitamab plus PolaR CHP. and this was also in frontline DLBCL where two cycles of chemotherapy for first use and then glofitamab was introduced in cycle three. And even in this study, they saw a very high CR rate of 90% and they had a shorter follow-up, but at 12 months, 95% of patients were still in remission. A very high MRD negative rate and again, CRS rate was very low at only 10%. Now, epcoritamab, the other bispecific antibody, was also tested with PolaR CHP. This was actually presented at the EHA meeting where epcoritamab was started in cycle one. And again, this saw very high response rates, very high CR rate of like 97%, but the CRS was higher. So it’s possible that like if you introduce bispecific antibody from cycle two or cycle three, that might lower the CRS rates. In the Epcore-Pola-CHP study, the CRS rate was 51%, although most of the CRS was all grade one, grade two. There was no grade three, grade four events. And about 20% of the patients needed to receive tocilizumab. So again, like, you know, just showing the combination of the, you know, how strong the efficacy is when you combine bispecific antibodies with frontline chemotherapy and DLBCL. The next key takeaways were actually relapsed/refractory DLBCL. And there were three large randomized studies which were presented, the POLARGO study, the SUNMO study, and also the STARGLO study. And these were all testing, you know, bispecific antibodies in combination versus R-GEMOX in relapsed/refractory DLBCL. and they all included patients who had, who are in the second line as well. So to start with the POLARGO study, which made it to the plenary session at ICML as well as at EHA, you know, this was looking at polatuzumab with gemcitabine, oxaliplatin, rituximab versus R-GEMOX. And this study included a significant number of primary refractory patients, about 50% of them were primary refractory. And it showed a significant improvement in PFS and OS with addition of polatuzumab to R-GEMOX compared to R-GEMOX. And then this, importantly, we thought like polatuzumab was going to only benefit in ABC subtype. But in this study, they saw improvements in both GCB as well as ABC subtype. The second study I’d like to talk about is the SUNMO study, which looked at fixed duration combination of mosunetuzumab plus polatuzumab, so combining a bispecific antibody with an ADC and comparing it with R-GEMOX. And, you know, in this study, again, over 50% patients were primary refractory. So that was close to almost 60% in this study was primary refractory. And the median PFS was significantly improved to 12 months compared to four months with R-GEMOX. And at 12 months, 49 or 50% of patients were actually in remission with Mosunetuzumab-Polatuzumab versus much lower with R-GEMOX. Median overall survival, the follow-up was short, but there was a trend to improvement. And benefits were across all key subgroups, including geographic location, lines of therapy, refractory disease. Very importantly, it was that the CRS was very low. So rare CRS events early, and they were early, they were low grade. So 26% CRS mostly was just a fever, this is grade one CRS. There were only like 4 or 5% grade two CRS and no grade three, grade four. And so majority of patients did not have CRS. And then only 4% of patients received steroids, only 4% received tocilizumab, so I think a very powerful combination with low toxicity, sort of, you know, in relapsed/refractory DLBCL would be a great option. There were no ICANS with this combination, and extremely well-tolerated with only 2% discontinuation rate for mosun-pola. And the third study, which was updated and, you know, already presented previously, but updated at ICML was the STARGLO study, which looked at fixed duration combination of glofitamab-GEMOX, to R-GEMOX. And in this study, the median prior lines of therapy was one, again, close to 60% primary refractory patients, similar to the SUNMO study. And there was a significant improvement in both median PFS as well as median overall survival with glofitamab-GEMOX compared to R-GEMOX. And at 18 months, nearly half the patients were still in remission with glofitamab-GEMOX. So what was updated at ICML was among patients who achieved a complete remission at end of treatment, about 80% or so were remaining progression-free at the longer follow-up. So there was a question about potential curability, although we have to wait a little bit longer. I think we could think about this as a potential curable regimen, especially if we see three years and four years, these patients are still maintaining a remission, especially if they underwent a complete remission. And I think that would be a huge advancement in the field. CRS was about 45%, you know, mostly low-grade CRS and very low ICANS, just 2%. Interestingly, we also participated in a mosune plus pola study in relapsed/refractory mantle cell lymphoma, which was also presented at ICML. And this had a very high overall response rate of 88% with nearly 80% CR rate. And interestingly, in the P53 mutated patients, it was like a 90% CR rate, which is really amazing to see, especially in the relapsed/refractory setting. And the responses were also durable because at 12 months, about two-thirds of the patients maintained the response. And the median PFS in the study was a little more than a year and a half. And this is very encouraging data, knowing that the population of patients treated in this relapsed/refractory mantle cell study with mosun-pola were 100% BTKi exposed, and 30% had failed a transplant, about one in four patients had failed CAR-T. And, you know, 40% of them had mutated P53. So very high-risk population. And you’re seeing like, you know, very high response rates, durable responses with mosun-pola. So I think mosun-pola was a big hit for both relapsed/refractory DLBCL, as well as relapsed/refractory mantle cell lymphoma. There was another study in relapsed/refractory DLBCL, which was presented again, going along with a theme of combining a bispecific antibody with ADC. And this was a single arm study of glofitamab plus loncastuximab in about 40 patients. But I think it was very interesting. Again, you know, over 50% were primary refractory. You know, they had, you know, really good responses in this study with CR rate of 87%. So really high and we don’t have a long-term follow-up with this study. But I think this is also a very powerful combination and probably will be studied in a wider population. One other study of combining chemotherapy with bispecific antibody was EPCO-RISE, which was actually presented with EHA with nearly 87% response rate and about two-thirds of patients achieved a CR. So I think this is an important study as well, because some late relapse patients may go for autologous transplant and achieving a complete remission before autologous transplant can drive outcomes after autologous transplant. So, you know, if you get a very high CR rate, which with Epco-R-ICE is achievable, I think that is very helpful. So I think that’s sort of like my takeaways for relapsed/refractory as well as frontline DLDCL and a little bit of segue into mantle cell lymphoma. Next I’ll talk about follicular lymphoma. And again, the same theme that follicular lymphoma, we have bispecific antibodies, epcoritamab, mosunetuzumab, approved in third line plus. And they’ve been moving up, in fact, moving up to even frontline. So the MorningSun study was presented with fixed duration mosunetuzumab subcute in frontline high tumor burden follicular lymphoma, and it showed a high overall response rate of 86% with 60% CR rate. And at 12 months, which is a short follow-up for a disease like follicular lymphoma, especially in the frontline setting, but it was encouraging to see that over 80% of patients were still in remission at 12 months. And remember, mosunetuzumab is fixed duration, So patients have already stopped therapy at that point. And CRS rate was about a third of patients had CRS. Mostly they were grade one. There were, in fact, no grade three or grade four CRS. Tocilizumab use was minimal, only 6% of patients had needed tocilizumab. And there was another study which was also presented for, you know, frontline use of mosunetuzumab subcute in high tumor burden follicular lymphoma. This was presented by Dr Falchi from Memorial Sloan Kettering. And in this study, overall response rate was even higher at 95% with CR rate of 82%. And again, with this study at 12 months, nearly 90% of patients here were still maintaining their remissions. CRS was, again, low grade for the most part. While I’ve talked so much about bispecific antibodies, I’d like to highlight that in relapsed/refractory follicular lymphoma, the inMIND study was presented by Dr Laurie Sehn at ICML. And this showed significant improvement in PFS with tafasitamab plus rituximab plus lenalidomide versus rituximab-lenalidomide with a median PFS of 22 months with tafa-R-squared versus 14 months with R-squared. The benefit was sustained across all subgroups. Time to next treatment was not reached with tafa-R-squared, and it was about 30 months or so with R-squared. There was no transformation seen in the Tafa arm, and nine patients had transformation in placebo arm, but it was not really powered to look at these differences, but these were just presented as raw values. I think this is important. The reason I mention it is around that time, the FDA did approve Tafa-rituximab-lenalidomide as a treatment option of relapsed/refractory follicular lymphoma. The last one I’d like to highlight was a study we were involved in looking at the influence of health disparities on clinical outcomes in patients with DLBCL in the U.S., and this was from large cooperative group studies. We found that race and ethnicity did not appear to drive clinical outcomes. In fact, high social deprivation index scores and lack of insurance or only public insurance corresponded with worse PFS and OS. And that was also presented by Dr [inaudible] at the ICML meeting.

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