FDA

Epkinly plus rituximab and lenalidomide OK’d for R/R follicular lymphoma

November 24, 2025

On November 18, 2025, FDA approved Epkinly (epcoritamab-bysp), a T-cell engaging bispecific antibody administered SC, in combination with rituximab and lenalidomide (EPKINLY + R2) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL).

Efficacy

Approval was based on results from the phase 3 EPCORE FL-1 study (NCT05409066) that evaluated fixed duration EPKINLY + R2 vs. standard of care R2. The study included a broad range of patients, including those with indolent to aggressive disease. In the study, EPKINLY + R2 reduced risk of disease progression or death by 79% (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.13% - 0.33%; p<0.0001) vs. standard of care R2 alone. In the dual primary endpoint of overall response rate (ORR), 89% of patients treated with EPKINLY + R2 responded to treatment (n=216/243; 95% CI, 84% - 93%; p<0.0001) vs. 74% of patients treated with R2 (n=181/245; 95% CI, 68%-79%). The median for dual primary endpoint of progression-free survival (PFS), wasn’t reached (NR) among patients treated with EPKINLY + R2 (95% CI, 21.9 months - NR) vs. 11.2 months for patients treated with R2 (95% CI, 10.5 months - NR). Among patients who were treated with EPKINLY + R2, 74% achieved a complete response (CR) (n=181/243; 95% CI, 69% - 80%; p<0.0001) vs. 43% of patients treated with R2 (n=106/245; 95% CI, 37% - 50%).

Safety

The safety profile of EPKINLY + R2 in the EPCORE FL-1 study was generally consistent with the known safety profiles of the individual regimens (epcoritamab and R2). The most common (≥ 20%) adverse reactions in patients who received EPKINLY + R2 were rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, cytokine release syndrome (CRS), pneumonia, COVID-19, and fever. The most common Grade 3 to 4 lab abnormalities (≥ 10%) were decreased neutrophil count, lymphocyte count, and platelets. CRS occurred in 24% of patients at the recommended 3 step-up dosage schedule, and was primarily low grade (19% Grade 1, 5% Grade 2). A single event of immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in one patient, grade 1 (0.8%). The prescribing information has a Boxed Warning for serious or life-threatening CRS and ICANS. Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity.

Sources:

Epkinly (epcoritamab-bysp) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761324s009lbl.pdf Revised November 2025. Accessed November 21, 2025.

AbbVie Announces U.S. FDA Approval of EPKINLY® (epcoritamab-bysp) in Combination with Rituximab and Lenalidomide for Relapsed or Refractory Follicular Lymphoma. [News release]. 2025. https://news.abbvie.com/2025-11-18-AbbVie-Announces-U-S-FDA-Approval-of-EPKINLY-R-epcoritamab-bysp-in-Combination-with-Rituximab-and-Lenalidomide-for-Relapsed-or-Refractory-Follicular-Lymphoma