ASH 2025 | Phase II results of rituximab and epcoritamab as 1L therapy for patients with high-tumor-burden FL

At ASH this year, we presented results from a phase two trial testing the combination of rituximab and epcoritamab for patients with newly diagnosed high tumor burden follicular lymphoma. So most patients for standard of care would receive chemoimmunotherapy, but CD3xCD20 bispecific antibodies are challenging the role of chemotherapy in this setting and could delay or obviate the need for chemo for some patients. So epcoritamab is a CD3xCD20 bispecific antibody that’s associated with high response rates, is already approved for relapsed or refractory follicular lymphoma. In this study, we hypothesized that four weekly doses of rituximab pretreatment before the first full dose of epcoritamab could both lower the risk of cytokine release syndrome and also deepen responses based on the distinct mechanisms by which these two drugs target CD20. Therapy in this study was time-limited, given over about nine months. 

So we enrolled 35 patients. They generally had high-risk features, including about 60% of patients with a high-risk FLIPI score. We observed very high response rates with a best overall response rate of 97% and a best complete metabolic response rate of 94%, both of which are high in this setting. Follow-up is still somewhat limited. Median follow-up is 12 and a half months, but we’ve observed no relapses in patients who had a response, and the one-year progression-free survival is 97%. 

The regimen was generally tolerable. CRS was observed in 46% of patients, but almost all of it was grade one. We saw grade two CRS in just two patients, or 6%, and no grade three or higher CRS, suggesting that rituximab pretreatment likely does lower the risk of cytokine release syndrome in this setting. Infections were seen in about 60% of patients but were generally low grade. There were five patients who had a grade three or higher infection; all of those infections resolved and patients were able to restart and complete therapy. 

So this regimen is very active and I think suggests that some patients, perhaps many patients, can have excellent results without chemotherapy or lenalidomide. Longer follow-up is, of course, needed to prove that, but based on these encouraging results, we’re currently enrolling a 65-patient expansion cohort to use this same combination, but with two small changes aimed at improving tolerance and convenience for patients. The first is decreasing the frequency of epcoritamab dosing during cycles four through nine. And the second is decreasing the steroid burden during epcoritamab dose ramp up. So we hope to have results from the expansion cohort to present to you soon.

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