Multinational phase 3 trial of addition of epcoritamab to lenalidomide-rituximab for relapsed or refractory follicular lymphoma

There is an unmet need for chemotherapy-free regimens that induce durable responses for relapsed or refractory follicular lymphoma (R/R FL). Lenalidomide and rituximab (R²) is an accepted standard of care in this population. The multinational phase 3 EPCORE FL-1 trial evaluated addition of epcoritamab (subcutaneous bispecific antibody directed to CD20 and CD3) to R² in patients with R/R FL after at least one previous line of chemotherapy. The trial, at 189 centers in 30 countries, randomized 243 patients to epcoritamab plus R² and 245 patients to R². Dual primary endpoints were overall response rate and progression-free survival by independent review. Wit a median follow-up of 14.8 months (IQR 11.4-19.0), overall response rate was 95% (95% CI 92-97) with epcoritamab plus R² versus 79% (74-84; p<0.0001) with R². Progression-free survival was longer with epcoritamab plus R² versus R², as were overall survival and time to next lymphoma treatment. Grade 3 or higher adverse events were more frequent with epcoritamab plus R² (90% versus 68%) Cytokine release syndrome in the epcoratimab group was low grade and manageable. The authors conclude that these findings position epcoritamab plus R2 as a new standard of care for second-line or subsequent treatment for R/R FL.