ICML 2025 | Key updates and takeaways in follicular lymphoma from ICML 2025: biology, trial updates, & more

I would like to share some highlights in follicular lymphoma from the Lugano meeting. So initially at the translational level, Dr Roulland presented new data using single-cell analysis to understand the follicular lymphoma heterogeneity. And their group identified 10 distinct follicular lymphoma subtypes, moving beyond the traditional idea of follicular lymphoma as a continuum between germinal center and memory B-cells. Importantly, these subtypes appear to have different clinical behaviors, and the group is now working to also combine microenvironment profiles. And I think one of the most interesting findings was that treatment responses varied by subtypes. So one group of patients had poor outcomes when they treated with R-CHOP chemotherapy, but those that treated with R-squared, rituximab and lenalidomide, did significantly better. And that suggested that molecular profiling could guide maybe treatment selection in follicular lymphoma. And so I think this is very important. 

And to go from there, so in terms of treatment advances, Dr Mankuzhyi from MSK presented data on a very low dose of radiation therapy. They compared patients that treated with 4 Gy to patients that were treated with a traditional 24 Gy. And those that treated with 4 Gy had similar progression rates. And that’s promising to know. And they are now, based on this finding, conducting a prospective trial to compare patients 4 Gy versus 24 Gy with limited stage follicular lymphoma. 

And then there was a study presented comparing ibrutinib-rituximab versus rituximab alone, for previously untreated patients, they were not eligible for chemotherapy. And they showed that for patients that were treated with rituximab-ibrutinib, there is higher progression-free survival. But there were a lot of criticisms around these eligibility criteria, who were the patients that are not eligible for chemotherapy. And also the control arm was rituximab alone, which is maybe not appropriate for treatment with high tumor burden follicular lymphoma. 

In another frontline study, Dr Falchi presented data on mosunetuzumab, a bispecific antibody, in newly diagnosed follicular lymphoma. A fixed duration regimen of mosunetuzumab resulted in a 95% overall response rate with 82% complete response rate, which looks very promising, and outcomes are definitely comparable to the standard immunochemotherapy that we give as standard of care now. And these results were consistent across all the subgroups, including high-risk patients, and there were no new safety signals observed. To mention, the follow-up is still very short, it’s around 17 months. And so these findings are interesting, but should follow longer follow-up for sure. 

And in the relapsd/refractory setting, Dr Sehn presented the Phase II trial, inMIND trial, which compared tafasitamab and rituximab to R-squared, and also this triplet significantly reduces the risk of progression, relapse or death, and the benefit was also consistent across different patient subgroups. And there was even a trend toward improved overall survival. So this combination was now approved by FDA because of this study, and that’s great to know. 

And lastly, and finally, Dr Casulo presented data from the LEO cohort and the transformation of follicular lymphoma. And we all know that in follicular lymphoma, transformation is one of the most important events and this changed patient trajectory. And they looked at patients with sequential transformation versus composite transformation, and they found significant differences for patients who had sequential transformation, especially those that were previously treated for the follicular lymphoma and were exposed to anthracycline, they had the worst prognosis. And those who transformed without prior treatment did better, but the composite lymphoma that were diagnosed at the same time with transformation, they were the more favorable. I think this suggests that transformation in follicular lymphoma also represents different clinical entities, and so there are different follicular lymphoma transformations with different biological behaviors. And the treatment history is very important as it may shape the transformation risk and outcomes. 

That’s all at Lugano- I think in follicular lymphoma, we learned a lot about follicular lymphoma biology and how this might guide our more smart, more personalized treatment strategies in the future.

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