U.S. FDA Approves Epcoritamab (Epkinly) for Follicular Lymphoma

On November 18, 2025, the U.S. Food and Drug Administration (FDA) approved epcoritamab-bysp (Epkinly, AbbVie) with rituximab (Rituxan, Genentech and Biogen) and lenalidomide (Revlimid, BMS) (R²) for adults with relapsed or refractory follicular lymphoma after at least one prior therapy. 

Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma that starts in B cells. About 15,000 people in the United States are diagnosed each year. People often respond well to first treatments, but many experience relapse. Some cases can also change into a faster-growing lymphoma, which can make ongoing treatment planning important.

Epcoritamab was first granted accelerated approval in June 2024 for people with follicular lymphoma who had tried at least two prior therapies. The new approval expands its use by allowing doctors to prescribe it earlier on in combination with rituximab and lenalidomide. 

"Recurrent follicular lymphoma can be an incurable, complex and persistent disease, creating a clear need for additional treatments that can change its course earlier in the treatment journey. The results shown with EPKINLY + R² in the EPCORE FL-1 study are incredibly meaningful, demonstrating durable responses compared to patients treated with R² alone. These data, delivered by a regimen that's chemotherapy-free and can be administered in the outpatient setting, suggest that EPKINLY + R² could potentially become a new standard of care." - Lorenzo Falchi, M.D., lymphoma specialist, department of medicine, Memorial Sloan Kettering Cancer Center.

How does epcoritamab with rituximab and lenalidomide treat follicular lymphoma?

Epcoritamab is a bispecific antibody that can connect two different cells at once. It attaches to the CD3 protein on T cells and the CD20 protein on follicular lymphoma cells. This helps the immune system find and remove the cancer cells more effectively. 

Rituximab is a monoclonal antibody. It attaches to the CD20 protein on follicular lymphoma cells and marks them so the immune system can recognize and clear them. Lenalidomide works by blocking signals that follicular lymphoma cells need to grow. It also activates certain immune cells so they can better attack cancer cells.

Epcoritamab is given as a subcutaneous injection (under the skin). During the first treatment cycle, doses are slowly increased using a “step-up” plan to lower the chance of side effects. Rituximab is given through an intravenous infusion, and lenalidomide is taken as a capsule by mouth. 

People receive epcoritamab in 28-day cycles for up to 12 cycles unless the follicular lymphoma grows or side effects outweigh the benefits of treatment. Lenalidomide is taken on days 1 through 21 of each cycle, and rituximab is given for the first 5 cycles. 

The study that led to the approval of epcoritamab + R² 

The Phase 3 EPCORE FL-1 trial included 488 adults with relapsed or refractory follicular lymphoma. Half received epcoritamab with rituximab and lenalidomide (R²), and half received standard R² treatment alone. Key results included: 

• Epcoritamab with R² lowered the risk of the cancer growing or death by 79% compared to R² alone.
• 89% of people taking epcoritamab with R² experienced remission, compared to 74% of people who received R² alone.
• At a median of 14.8 months since starting treatment, more than half of the people taking epcoritamab with R² were still alive and continued to have control over their cancer. For people who received R² alone, the median amount of time the treatment delayed cancer growth or death was 11.2 months. 

What are the common side effects of the epcoritamab + R²?

The most common side effects of epcoritamab + R² for people with follicular lymphoma were: 

• Rash
• Upper respiratory tract infections
• Fatigue
• Injection site reactions
• Constipation
• Diarrhea
• Cytokine release syndrome (CRS)
• Pneumonia
• COVID-19
• Fever
• Decreased white blood cells and decreased platelets 

During the clinical trial, fewer than 15% of patients stopped treatment due to side effects.  

Next steps for people living with follicular lymphoma

If you or a loved one has follicular lymphoma, ask your healthcare team about how your current treatment is working for you and if epcoritamab with rituximab and lenalidomide (R²) or ongoing studies may be right for you. 

Questions to ask your care team about epcoritamab + R²

Consider asking your care team the following questions about the combination of epcoritamab + R²: 

• How does epcoritamab + R² compare to my current treatment?
• What side effects should I watch for, and when should I call the clinic?
• How often will I need to come in for treatment?
• Will I need someone with me during the step-up dosing phase?
• What financial resources are available for this treatment? 

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Sources:

• AbbVie Announces U.S. FDA Approval of EPKINLY® (epcoritamab-bysp) in Combination with Rituximab and Lenalidomide for Relapsed or Refractory Follicular Lymphoma
• FDA approves epcoritamab-bysp for follicular lymphoma indications
• EPKINLY Prescribing Information