On November 18, 2025, the US Food and Drug Administration approved epcoritamab-bysp in combination with rituximab and lenalidomide for adult patients with relapsed or refractory follicular lymphoma (FL). On the same day, the FDA also converted the prior accelerated approval of epcoritamab-bysp monotherapy in patients with FL who have received at least two prior lines of systemic therapy to full approval.

The combination approval was supported by data from EPCORE FL-1 (Study M20-638; NCT05409066), a phase 3, open-label, randomized trial enrolling 488 patients with relapsed or refractory FL. Patients were randomized 1:1 to receive epcoritamab-bysp with rituximab and lenalidomide (R²) or R² alone. The coprimary endpoints were progression-free survival (PFS) and overall response rate (ORR) assessed by independent review per Lugano 2014 criteria. ORR was 89% (95% CI, 84–93) in the epcoritamab arm compared to 74% (95% CI, 68–79) in the control arm. Median PFS was not reached in the epcoritamab arm (95% CI, 21.9 months–not reached) and was 11.2 months (95% CI, 10.5–not reached) in the R² arm, corresponding to a hazard ratio of 0.21 (95% CI, 0.13–0.33; P < .0001).

Treatment-related adverse events included cytokine release syndrome (CRS) in 24% of patients (12% serious) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 0.8%. Serious adverse reactions occurred in 51% of patients, including serious infections in 28%. Common adverse events (≥20%) included injection-site reactions, CRS, fatigue, upper respiratory tract infections, rash, diarrhea, pyrexia, cough, and headache. Grade 3–4 cytopenias included neutropenia (~30%), anemia (~10%), and thrombocytopenia (~8%). Epcoritamab-bysp is administered subcutaneously with a cycle 1 step-up dosing regimen followed by weekly and then every 4-week maintenance dosing.

This approval offers a fixed-duration, outpatient, chemotherapy-free treatment option for relapsed or refractory FL, a disease marked by inevitable relapse and treatment resistance. The addition of epcoritamab-bysp to R² provides a novel immunotherapeutic strategy with clinically meaningful improvements in PFS and response rates.

References:

US Food and Drug Administration. FDA approves epcoritamab-bysp for follicular lymphoma indications. FDA. Published November 18, 2025. Accessed November 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-epcoritamab-bysp-follicular-lymphoma-indications