First-line treatment with epcoritamab in combination with bendamustine plus rituximab induces sustained remissions beyond 3 years in patients with follicular lymphoma.

First-line (1L) bendamustine plus rituximab (BR) leads to high response rates in follicular lymphoma (FL), but maintaining durable remissions remains challenging. We report the 3-year follow-up from arm 3 of the phase 1b/2 EPCORE NHL-2 trial (NCT04663347) of epcoritamab, a subcutaneously administered CD3×CD20 bispecific antibody, combined with BR in patients with newly diagnosed FL. Twenty-five patients received epcoritamab plus BR, followed by epcoritamab monotherapy for up to 2 years. At a median follow-up of 41.3 months, the best overall response and CR rates were both 96%. The median time to CR was 1.5 (range 1-6) months. At 3 years, 87% of responders maintained CR. High CR rates were observed across subgroups, including 100% of patients with bulky disease (≥7 cm), 93% with Follicular Lymphoma International Prognostic Index score ≥3, and 100% with bone marrow involvement. The three-year progression-free survival and overall survival rates were 83% and 96%, respectively. Three patients progressed within 24 months of initiating treatment. Long-term data were consistent with prior reports and the known safety profiles of the individual agents, with no high-grade cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome events. Infections occurred in 92% of patients; COVID-19 was the most common (84%). Overall, 1L FL treatment with epcoritamab plus BR resulted in deep, durable responses beyond 3 years with a consistent safety profile. These results compare favorably with BR alone, although they require confirmation in further studies, and highlight the versatility of epcoritamab in combination with various standards of care and in improving outcomes in FL.