Epcoritamab Enhances Outcomes in Second-Line Follicular Lymphoma Treatment

In a study presented at the 2025 American Society of Hematology Annual Meeting, epcoritamab added to second-line rituximab–lenalidomide (R2) significantly improved response and progression-free survival in relapsed/refractory follicular lymphoma. The trial reported a 95.1% overall response rate and an 85.5% PFS versus 79.2% and 40.2% with R2 alone, strengthening the case for a chemo-free second-line option.

Against historical outcomes with R2, which produced substantial but more modest depths of response, the combination meaningfully increased complete responses and time without progression. Because R2 is an established chemo-sparing second-line regimen, adding a bispecific to deepen responses without mandating cytotoxic chemotherapy is clinically notable and may prompt rethinking of sequencing toward chemo-free strategies.

The randomized second-line trial showed an ORR of 95.1% versus 79.2%, a CR rate of 82.7% versus 49.8%, and a PFS of 85.5% versus 40.2% for the experimental and control arms, respectively. ORR, CR, and PFS were primary endpoints.

Safety signals included increased hematologic toxicities and infection-related events, alongside low-grade cytokine-release phenomena and other immune-related adverse events. The report did not highlight grade 3–4 CRS or unexpected high-grade neurologic toxicity. Overall tolerability in the trial was manageable in an outpatient setting; higher rates of grade 3–4 events were driven mainly by cytopenias.