Epcoritamab With Rituximab Plus Lenalidomide Approved for R/R Follicular Lymphoma in Second Line

The FDA has approved the bispecific antibody epcoritamab-bysp (Epkinly; Genmab/AbbVie) in combination with rituximab (Rituxan) and lenalidomide (Revlimid), also known as R², to treat adult patients with follicular lymphoma (FL) who have relapsed for the first time.

Epcoritamab, previously approved for FL and for diffuse large B-cell lymphoma after patients have received at least 2 prior treatments, is now the only bispecific therapy approved in second-line treatment of FL. Genmab announced the approval in a statement.

“Recurrent follicular lymphoma can be an incurable, complex, and persistent disease, creating a clear need for additional treatments that can change its course earlier in the treatment journey,” Lorenzo Falchi, MD, a lymphoma specialist from the Department of Medicine at Memorial Sloan Kettering Cancer Center, said in the statement from Genmab. “The results shown with [epcoritamab] + R² in the EPCORE FL-1 study are incredibly meaningful, demonstrating durable responses compared to patients treated with R² alone. These data, delivered by a regimen that’s chemotherapy-free and can be administered in the outpatient setting, suggest that [epcoritamab] + R² could potentially become a new standard of care.”

FL, the second most common type of non-Hodgkin lymphoma, is a slow-growing disease that accounts for 20% to 30% of all cases; it affects approximately 15,000 people per year in the US. FL is considered treatable but not curable, and the duration of each remission grows shorter with each relapse. Thus, the arrival of a fixed-duration regimen that offers extended progression-free survival (PFS) is an important development from a managed care perspective, as it promises patients a possible break from treatment as well as cost savings.

Approval is based on results from the phase 3 EPCORE FL-1 trial (NCT05409066), in which fixed-duration epcoritamab plus R² reduced the risk of disease progression or death by 79% (HR, 0.21; 95% CI, 0.13-0.33; P < .0001), compared with R² alone. Median PFS was not reached among those patients receiving the epcoritamab plus R² regimen, compared with 11.2 months for those treated with R². Patients received the regimen in 28-day cycles for 12 cycles or until disease progression or unacceptable toxicity, whichever occurred first.

Safety results from the epcoritamab plus R² combination in EPCORE FL-1 were generally consistent with the known profiles of individual regimens. Common adverse events 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 laboratory abnormalities, affecting at least 10% of patients, were decreased neutrophil count, lymphocyte count, and platelets.

CRS occurred in 24% of patients at the recommended 3 step-up dosing schedule; 19% of patients experienced grade 1 CRS, with 5% experiencing grade 2. One patient had a grade 1 event of immune effector cell–associated neurotoxicity syndrome (ICANS). FDA has included a boxed warning for serious or fatal CRS and ICANS.

“The FDA approval of EPKINLY + R² is an important advancement for patients with follicular lymphoma, enabling treatment at initial recurrence when more effective intervention is needed,” Judith Klimovsky, MD, executive vice president and chief development officer of Genmab, said in the statement. “This milestone also underscores EPKINLY’s potential as the core therapy for B-cell malignancies, demonstrating benefit in combination and earlier disease, and building on its established role as a single agent option in later lines of treatment.”

With the results from the confirmatory phase 3 EPCORE FL-1 study, the FDA has also converted the accelerated approval into a full approval. Data from the phase 3 EPCORE FL-1 study will be presented at the Annual Meeting and Exposition of the American Society of Hematology in December.

Reference

Genmab announces EPKINLY (epcoritamab-bysp) in combination with rituximab and lenalidomide approved by the U.S. Food and Drug Administration for the treatment of relapsed or refractory follicular lymphoma. News release. BusinessWire. November 18, 2025. Accessed November 18, 2025. https://www.businesswire.com/news/home/20251118608941/en/Genmab-Announces-EPKINLY-epcoritamab-bysp-in-Combination-with-Rituximab-and-Lenalidomide-Approved-by-the-U.S.-Food-and-Drug-Administration-for-the-Treatment-of-Relapsed-or-Refractory-Follicular-Lymphoma