The U.S. Food and Drug Administration (FDA) has approved Epkinly (epcoritamab-bysp) plus Revlimid (lenalidomide) and Rituxan (rituximab) for the treatment of patients with relapsed or refractory follicular lymphoma (FL), according to an update from the regulatory agency.
Moreover, traditional approval was also granted for Epkinly monotherapy in relapsed or refractory FL after two or more lines of systemic therapy, following the drug’s accelerated approval for this indication in 2024, the update noted.
The approval of Epkinly with Revlimid and Rituxan was supported by findings from the EPCORE FL-1 clinical trial, which enrolled 488 patients with relapsed or refractory FL who were evenly randomized to receive Revlimid and Rituxan with or without Epkinly. Patients had received a median of one prior systemic therapy, with 24% and 17% having received two or three or more prior lines, respectively.
The study, according to the FDA release, showed superior progression-free survival and overall response rate in the Epkinly arm. The progression-free survival hazard ratio was 0.21, with the median progression-free survival not reached in the Epkinly arm and 11.2 months in the control arm. The overall response rate reached 89% in the Epkinly arm compared with 74% in the control arm.
According to the FDA, prescribing information for the regimen includes boxed warnings for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), along with warnings and precautions for infections and cytopenias.
Serious side effects occurred among 51% of patients treated with Epkinly, including serious infections in 28%, cytokine release syndrome in 24%, serious cytokine release syndrome in 12% and ICANS in 0.8%.
The agency also noted that the recommended regimen for Epkinly, Revlimid and Rituxan consists of subcutaneous administration of Epkinly for up to 12 28-day cycles, with Revlimid on days 1 to 21 of each cycle and Rituxan for five cycles.
More About the Epkinly Plus Revlimid and Rituxan Treatment Combination
Earlier this year, it was announced that among adult patients with relapsed or refractory FL, the combination of subcutaneous Epkinly with Rituxan and Revlimid, compared with Rituxan and Revlimid alone, reduced the risk of disease progression or death by 79%.
These findings came from a pre-planned interim analysis from the phase 3 EPCORE FL-1 clinical trial, announced in a news release by Epkinly manufacturer Genmab A.S., and were scheduled for submission for presentation at the 67th Annual Meeting and Exposition of the American Society of Hematology, which will be held Dec. 6 to 9 in Orlando, Florida.
“The nature of follicular lymphoma lies in the underlying pathogenesis. Essentially, this is a disease that is generally indolent, so it's generally slow growing, waxing and waning, but currently with our available therapies, it's still considered incurable, and so especially for our patients who are diagnosed at a younger age, there is a need for better therapies, or more therapies that will essentially prolong, that will help get the disease under control and actually control the disease for a long time. Ideally, we want this condition, obviously, to be curable. We want to be able to cure this, but I think at the end of the day, we want to make sure that this does not harm our patients or cause complications with their daily life,” Dr. Christina Poh, physician at Fred Hutch Cancer and assistant professor at the University of Washington School of Medicine, said in a 2024 interview with CURE.
References
- “FDA approves epcoritamab-bysp for follicular lymphoma indications,” by the U.S. FDA. News release; Nov. 18, 2025.
- “Epkinly Combo Reduces Risk of Progression or Death in Follicular Lymphoma,” by Alex Biese. CURE; Aug. 8, 2025. https://www.curetoday.com/view/epkinly-combo-reduces-risk-of-progression-or-death-in-follicular-lymphoma
- “What is Follicular Lymphoma and Why Are Better Treatments Needed,” by Alex Biese. CURE; Dec. 19, 2025. https://www.curetoday.com/view/what-is-follicular-lymphoma-and-why-are-better-treatments-needed-
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