Epcoritamab (CD3×CD20) + R² Drives 95% ORR in Frontline Follicular Lymphoma—But Infection Risk Looms

Epcoritamab is a subcutaneous CD3×CD20 T-cell–engaging bispecific antibody, here added to the chemotherapy-free backbone of rituximab + lenalidomide (R²) as first-line therapy. In the open-label, multicentre EPCORE NHL-2 Phase 1b/2 Arm 6 trial (NCT04663347), previously untreated CD20+ grade 1–3A follicular lymphoma patients (n=41) received rituximab + lenalidomide for 12 cycles plus step-up–dosed epcoritamab followed by less frequent dosing for up to 2 years; at median 35.9 months’ follow-up, investigator-assessed ORR was 95% (39/41; 95% CI 84–99). Grade 3–4 AEs were led by neutropenia (49%) and infections (29%); serious AEs occurred in 71% (including CRS 32% and serious infections 32%), with 3 treatment-related deaths (7%; septic shock, PML, COVID-19)—a materially higher “high-grade infection/immune-toxicity” burden than historical R² alone in untreated FL, which delivers similar disease control to rituximab-chemo (e.g., RELEVANCE) without bispecific-driven CRS.