Multinational phase 1-2b trial of first-line epcoritamab with rituximab and lenalidomide for follicular lymphoma

Chemotherapy-free regimens, such as rituximab and lenalidomide, are attractive first-line treatment options for follicular lymphoma (FL), but combinations providing deeper and more durable responses are needed. Arm 6 of the phase 1-2b EPCORE NHL-2 trial, at 20 centers in six European countries, evaluated the combination of epcoritamab (a subcutaneously adminstrated CD3 x CD20 bispecific antibody) plus rituximab and lenalidomide as first-line treatment for CD20⁺, grade 1-3A FL in patients with an ECOG performance status 0-2. The primary endpoint was investigator-assessed overall response rate (ORR). Arm 6 included 41 patients, who received epcoritamab-rituximab-lenalidomide for up to 2 years. At a median follow-up of 35.9 months (IQR 35.8-36.6), the ORR was 95% (95% CI 84-99). Median time to response was 2.7 months, and median time to complete response (in 88% of patients) was2.8 months. Median duration of response, median progression-free survival and median overall survival were not reached. The most common grade 3-4 adverse events were neutropenia (49% of patients), infections (29%), COVID-19 (15%), and alanine aminotransferase increase (12%). Serious adverse events occurred in 71%, and treatment-related deaths in 7%. The authors conclude that epcoritamab plus rituximab-lenalidomide showed high activity in first-line treatment for FL.