Pune, India | November 19, 2025
The U.S. Food and Drug Administration (FDA) has granted full approval to epcoritamab-bysp (Epkinly) in combination with lenalidomide and rituximab. For adults with relapsed or refractory follicular lymphoma (FL). Previously, the FDA had given Epkinly accelerated approval for monotherapy in FL after patients had received two or more lines of systemic therapy. Subsequently, the agency converted this provisional approval into traditional approval, relying on robust evidence from a randomized Phase 3 clinical trial.
The EPCORE FL 1 trial enrolled 488 patients experiencing relapsed or refractory FL. Participants received either Epkinly plus lenalidomide-rituximab (R²) or R² alone. Consequently, trial results strongly favored the Epkinly combination arm. The hazard ratio for disease progression or death (PFS) reached 0.21, accompanied by a highly significant p-value below 0.0001.
In addition, the overall response rate (ORR) achieved 89% in the Epkinly-plus-R² group, compared to 74% in the control arm. Meanwhile, the median progression-free survival in the experimental arm remained unreached, whereas it measured 11.2 months for the control group. Despite these impressive outcomes, clinicians must carefully monitor patient safety. The prescribing information carries boxed warnings for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).
During the trial, 51% of patients in the Epkinly arm experienced serious adverse events. Notably, serious infections affected 28% of participants. CRS occurred in 24% of patients, with 12% experiencing severe cases. ICANS was rare, appearing in only 0.8% of participants. Clinicians should therefore remain vigilant and manage these events according to established protocols.
The recommended treatment schedule administers Epkinly via subcutaneous injection over twelve 28-day cycles. Lenalidomide is given on Days 1–21, while rituximab is administered for five cycles. To mitigate CRS risk, clinicians follow a step-up dosing schedule during Cycle 1: 0.16 mg on Day 1, 0.8 mg on Day 8, 3 mg on Day 15, and the full 48 mg on Day 22. After Cycle 1, patients continue Epkinly weekly during Cycles 2 and 3, then every four weeks from Cycle 4 through Cycle 12.
The FDA evaluated Epkinly using a Summary Review supported by the Assessment Aid, a voluntary submission that streamlined regulatory assessment. Additionally, the therapy had received Breakthrough Therapy Designation, Priority Review, and Orphan Drug Designation, highlighting the urgent need for effective FL treatments.
AbbVie, co-developing Epkinly with Genmab, celebrated the approval. The company emphasized that this marks the first FDA authorization for a bispecific antibody combination therapy in lymphoma, potentially transforming standard FL care. Dr. Lorenzo Falchi of Memorial Sloan Kettering Cancer Center described the trial outcomes as “incredibly meaningful,” noting that the chemotherapy-free, outpatient regimen may become a future standard of care.
Meghan Gutierrez, CEO of the Lymphoma Research Foundation, also highlighted the approval as significant progress for FL patients. She noted that broader access to bispecific therapy could deliver advanced treatment closer to patients’ homes across diverse clinical settings.
The Phase 3 results from EPCORE FL 1 will be presented at the American Society of Hematology (ASH) annual meeting in December 2025. In the meantime, healthcare professionals should report serious adverse events related to Epkinly via the FDA’s MedWatch system.
This new approval represents Epkinly’s third FDA indication, following its prior approval for diffuse large B-cell lymphoma (DLBCL). It also underscores the promise of bispecific T-cell engagers in B-cell malignancies, offering renewed hope to patients worldwide.
