Written By: Pharmacally Medical News Desk
AbbVie on 18 November 2025 has announced the U.S. Food and Drug Administration (FDA) approval of EPKINLY® (epcoritamab-bysp) in combination with rituximab and lenalidomide (R²) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). This approval marks a significant milestone as EPKINLY becomes the first bispecific antibody approved for follicular lymphoma in the second-line and beyond setting.
EPKINLY is a subcutaneously administered T-cell engaging bispecific antibody that targets CD20 on B cells and CD3 on T cells, effectively redirecting T cells to eliminate malignant B cells. The new indication expands upon earlier accelerated FDA approval granted in June 2024 for EPKINLY monotherapy in patients with R/R FL after two or more prior systemic therapies.
The FDA approval of the combination therapy is based on pivotal Phase III data from the EPCORE FL-1 trial (NCT05409066), which demonstrated that EPKINLY plus rituximab and lenalidomide significantly reduced the risk of disease progression or death by 79% compared to the standard rituximab and lenalidomide regimen alone. The regimen offers a chemotherapy-free treatment option, potentially shifting the therapeutic paradigm for patients with relapsed or refractory FL.
Safety considerations include risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which led to a Boxed Warning on the label. Most adverse events reported were manageable and consistent with known effects of T-cell engaging therapies.
During treatment with EPKINLY, patients should be closely monitored for signs of cytokine release syndrome (CRS), a common and potentially serious side effect. Symptoms of CRS include fever, low blood pressure, difficulty breathing, and fatigue. Patients are advised to promptly report any such symptoms to their healthcare provider. Treatment protocols involve withholding EPKINLY until CRS symptoms resolve, and supportive therapies such as corticosteroids or intensive care may be necessary for severe cases. Pre-medication and step-up dosing schedules are used to reduce the risk and severity of CRS. Patients should also stay well-hydrated and work closely with their medical team for timely management of any adverse reactions during therapy.
In June 2024, the FDA has granted accelerated approval to EPKINLY monotherapy for the treatment of relapsed or refractory follicular lymphoma (R/R FL) following two or more prior systemic therapies. Following positive confirmatory results from the Phase 3 EPCORE FL-1 study, the FDA has now converted this accelerated approval to full traditional approval, cementing EPKINLY’s role as an established treatment option in this setting.
Meghan Gutierrez, CEO of Lymphoma Research Foundation, said, “This milestone offers people with follicular lymphoma access to a bispecific therapy that can be given closer to home in diverse medical settings.”
Daejin Abidoye, MD, AbbVie VP and oncology head, stated, “EPKINLY is now the first bispecific antibody approved for second-line plus follicular lymphoma, addressing urgent needs for better options in relapsed or refractory disease.”
Lorenzo Falchi, MD, lymphoma specialist at Memorial Sloan Kettering Cancer Center, noted, “Recurrent follicular lymphoma remains complex and incurable, highlighting the need for treatments that alter its trajectory earlier. EPKINLY plus R² shows durable responses and could become a new outpatient chemotherapy-free standard of care.”
In summary, the FDA approval of EPKINLY combined with rituximab and lenalidomide offers a new, effective, and chemotherapy-free treatment approach for patients with relapsed or refractory follicular lymphoma, founded on robust Phase III clinical trial evidence that demonstrates superior progression-free survival over existing standards of care.
References
AbbVie Announces U.S. FDA Approval of EPKINLY® (epcoritamab-bysp) in Combination with Rituximab and Lenalidomide for Relapsed or Refractory Follicular Lymphoma, 18 November 2025, AbbVie, https://news.abbvie.com/2025-11-18-AbbVie-Announces-U-S-FDA-Approval-of-EPKINLY-R-epcoritamab-bysp-in-Combination-with-Rituximab-and-Lenalidomide-for-Relapsed-or-Refractory-Follicular-Lymphoma
Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease Activity in Adult Participants With Follicular Lymphoma (EPCORE FL-1), ClinicalTrials.gov ID NCT05409066, https://clinicaltrials.gov/study/NCT05409066
Lorenzo Falchi et al, EPCORE FL-1: Phase 3 Trial of Subcutaneous Epcoritamab with Rituximab and Lenalidomide (R 2) Vs R 2 Alone in Patients with Relapsed or Refractory Follicular Lymphoma. Blood 2023; 142 (Supplement 1): 3053. Doi: https://doi.org/10.1182/blood-2023-180092