FDA Approves AbbVie’s EPKINLY Combination for Relapsed or Refractory Follicular Lymphoma

The U.S. Food and Drug Administration (FDA) has approved AbbVie’s EPKINLY® (epcoritamab-bysp), a subcutaneously administered T-cell engaging bispecific antibody, in combination with rituximab and lenalidomide (EPKINLY + R2) for adults with relapsed or refractory (R/R) follicular lymphoma (FL). The decision is based on the pivotal Phase 3 EPCORE® FL-1 trial, which demonstrated the combination’s significant improvements over the standard R2 regimen.

Follicular lymphoma, an indolent form of non-Hodgkin lymphoma, affects about 15,000 people in the U.S. annually. Although treatable, FL is considered incurable with existing therapies and often relapses. In some cases, it progresses into a more aggressive condition such as diffuse large B-cell lymphoma.

The EPCORE FL-1 study showed that EPKINLY + R2 reduced the risk of disease progression or death by 79% compared to R2 alone. The overall response rate reached 89% with the combination therapy versus 74% with R2, and 74% of patients achieved a complete response—substantially higher than the 43% recorded among patients receiving R2 alone. Median progression-free survival was not reached in the EPKINLY + R2 group, compared with 11.2 months for the control arm.

Dr. Lorenzo Falchi of Memorial Sloan Kettering Cancer Center highlighted the significance of the results, noting that the regimen’s durability of response and chemotherapy-free nature “could potentially become a new standard of care.”

The safety profile of the combination was consistent with known effects of epcoritamab and R2. Common adverse reactions included rash, fatigue, injection site reactions, infections, diarrhea and constipation. Cytokine release syndrome occurred in 24% of patients but was mostly low grade. The treatment carries a boxed warning for serious CRS and ICANS.

Advocacy groups welcomed the approval. Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said it expands access to a therapy that can be administered in a variety of care settings, including closer to patients’ homes.

EPKINLY + R2 previously received Breakthrough Therapy Designation. The new approval also converts EPKINLY’s earlier accelerated approval for R/R FL into a full approval, based on confirmatory Phase 3 data. AbbVie says it will continue pursuing global regulatory submissions, with full results of the EPCORE FL-1 trial scheduled for presentation at the 2025 ASH Annual Meeting.