Pune, India | November 19, 2025
The U.S. Food and Drug Administration (FDA) has granted full approval for epcoritamab-bysp (Epkinly). Consequently, this approval permits its use in combination with lenalidomide and rituximab for adults battling relapsed or refractory follicular lymphoma (FL).
Initially, the FDA gave Epkinly accelerated approval for use as a monotherapy. This earlier approval covered FL patients who had already undergone two or more lines of systemic therapy. Subsequently, the agency officially converted that provisional approval into traditional approval. This decision stems from the powerful and persuasive evidence collected during a large, randomized Phase 3 clinical trial.
The crucial EPCORE FL 1 trial enrolled 488 total patients suffering from relapsed or refractory FL. The study randomly assigned participants to receive one of two treatment regimens. Specifically, they received either Epkinly plus lenalidomide-rituximab (R²) or R² alone, which served as the control arm. Results overwhelmingly favored the Epkinly combination arm over the control arm. For instance, the hazard ratio for disease progression or death (PFS) reached an impressive 0.21. Furthermore, the accompanying p-value was statistically significant, falling below 0.0001, which establishes high confidence in the findings.
The combination arm achieved an overall response rate (ORR) of 89%. Conversely, the control group only reported an ORR of 74%. In addition, the median progression-free survival in the experimental arm remains unreached to date. By contrast, the control group experienced a median PFS of 11.2 months. This marked difference highlights the profound clinical benefit of the Epkinly regimen.
Despite the positive efficacy data, clinicians must monitor patient safety with extreme vigilance. The prescribing information for Epkinly carries boxed warnings regarding two critical adverse events. These include cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).
During the EPCORE FL 1 trial, 51% of patients receiving Epkinly experienced serious adverse events. Notably, serious infections occurred in 28% of the trial participants. CRS presented in 24% of patients; however, only 12% of those experienced serious CRS events. Fortunately, ICANS proved rare, appearing in just 0.8% of patients receiving the combination therapy. Therefore, careful risk mitigation is essential for this treatment.
The recommended regimen delivers Epkinly via a subcutaneous injection. This administration schedule spans twelve total 28-day cycles. Lenalidomide is administered for 21 days (Days 1–21) of each cycle, while rituximab is given only during the first five cycles.
Clinicians follow a specific step-up dosing schedule during Cycle 1 to significantly mitigate the risk of CRS. The dosing schedule increases sequentially: 0.16 mg on Day 1, 0.8 mg on Day 8, 3 mg on Day 15, and finally the full 48 mg on Day 22. After patients complete Cycle 1, they receive Epkinly weekly throughout Cycles 2 and 3. Subsequently, patients move to an every-4-weeks schedule, continuing from Cycle 4 through Cycle 12.
The FDA reviewed Epkinly efficiently using a Summary Review process. This review was greatly aided by the Assessment Aid, a voluntary submission provided by the manufacturer to streamline the evaluation. Furthermore, the drug previously received several key designations. These included Breakthrough Therapy Designation, Priority Review, and Orphan Drug Designation. These designations emphasized the significant, urgent need for effective new follicular lymphoma therapies.
AbbVie, which co-developed Epkinly with Genmab, celebrated this landmark approval. The company proudly noted that this marks the first-ever FDA approval for a bispecific antibody used in a combination therapy for lymphoma. AbbVie strongly emphasizes the potential of this regimen to reshape the follicular lymphoma treatment landscape.
Dr. Lorenzo Falchi of Memorial Sloan Kettering Cancer Center described the trial results as “incredibly meaningful” for the patient community. He additionally stated that this chemotherapy-free, outpatient regimen could potentially become a new standard of care in the near future.
Meghan Gutierrez, CEO of the Lymphoma Research Foundation, commented that the approval marks significant progress for individuals living with follicular lymphoma. She highlighted that increasing patient access to bispecific therapy in diverse clinical settings brings powerful treatments closer to patients’ homes, greatly improving quality of life.
The detailed Phase 3 results from EPCORE FL 1 will be formally presented at the American Society of Hematology (ASH) annual meeting in December 2025. Meanwhile, healthcare professionals must report any serious adverse events related to Epkinly promptly through the FDA’s MedWatch system.
This approval now represents Epkinly’s third clinical indication. It follows the drug’s earlier approval for treating diffuse large B-cell lymphoma (DLBCL). Consequently, this successful development strongly reinforces the therapeutic potential of bispecific T-cell engagers in treating various B-cell malignancies. Ultimately, this new option offers much-needed hope to patients worldwide struggling with follicular lymphoma.
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