The European Commission has approved TEPKINLY (epcoritamab) plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma after at least one prior therapy, becoming Europe’s first bispecific antibody-based second-line treatment supported by Phase 3 EPCORE FL-1 results.
Written By: Kirti Kumbhar,
M.Pharm (QA)
Reviewed By: Pharmacally Editorial Team
The European Commission (EC) has approved TEPKINLY® (epcoritamab) in combination with lenalidomide and rituximab (R2) for the treatment of adults with relapsed or refractory (R/R) follicular lymphoma (FL) after at least one prior line of therapy. The decision makes TEPKINLY + R2 the first and only bispecific antibody-based therapy approved in Europe for second-line follicular lymphoma, introducing a fixed-duration, chemotherapy-free treatment option supported by positive Phase 3 data.
Phase 3 EPCORE FL-1 Met Dual Primary Endpoints
The approval is based on findings from the global Phase 3 EPCORE FL-1 trial (NCT05409066), which enrolled 488 patients with relapsed or refractory follicular lymphoma following at least one prior therapy. Patients were randomized to receive TEPKINLY + R2 (n=243) or standard R2 alone (n=245).
The study met both dual primary endpoints. TEPKINLY + R2 reduced the risk of disease progression or death by 79% compared with R2 alone (HR 0.21; 95% CI, 0.13-0.33; p<0.0001). The combination also produced a significantly higher overall response rate (ORR) of 96%, versus 81% with R2 alone (p<0.0001), while 74% of patients achieved a complete response, compared with 43% in the control arm. The pivotal results were published in The Lancet in January 2026.
Earlier Chemotherapy-Free Option for a Relapsing Disease
Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma and remains incurable despite its generally slow-growing course. Most patients eventually relapse, with remissions becoming progressively shorter after successive therapies. The EC approval introduces a new chemotherapy-free treatment option earlier in the disease course, where improving the depth and durability of response may help delay disease progression.
Epcoritamab is a subcutaneous CD3×CD20 bispecific IgG1 antibody developed using Genmab’s DuoBody® technology. By simultaneously binding CD3-positive T cells and CD20-positive malignant B cells, the therapy redirects the patient’s immune system to eliminate lymphoma cells.
Safety Profile Consistent with Previous Experience
The safety profile of TEPKINLY + R2 was consistent with the known safety profiles of epcoritamab and the R2 regimen, with no new safety signals identified. Serious adverse reactions occurred in 44% of treated patients, most commonly cytokine release syndrome (CRS), pneumonia, COVID-19, and febrile neutropenia. Frequently reported adverse events included neutropenia, rash, upper respiratory tract infections, fatigue, diarrhea, anemia, thrombocytopenia, hypogammaglobulinemia, and injection-site reactions.
Experts See Potential to Shift Second-Line Treatment
Catherine Thieblemont, MD, PhD, of Paris Cité University and Hôpital Saint-Louis, said the EPCORE FL-1 results demonstrate clinically meaningful improvements that could change second-line treatment by offering patients durable responses without chemotherapy.
AbbVie Chief Scientific Officer Roopal Thakkar, MD, said the approval expands treatment options for patients across Europe and addresses an important unmet need in relapsed or refractory follicular lymphoma.
Mitchell Smith, MD, PhD, Chief Medical Officer of the Follicular Lymphoma Foundation, added that the approval provides an important new option for patients facing repeated cycles of relapse and retreatment.
Development Program Continues Across B-Cell Malignancies
Epcoritamab is marketed as TEPKINLY® in the European Union and EPKINLY® in the United States and Japan and is approved for lymphoma indications in more than 65 territories. AbbVie and Genmab continue to evaluate the bispecific antibody across multiple Phase 3 studies, including earlier lines of follicular lymphoma and diffuse large B-cell lymphoma, as they pursue additional regulatory approvals and expand its role across B-cell malignancies.
Overall, the EC approval establishes TEPKINLY + R2 as the first bispecific antibody-based regimen available for second-line follicular lymphoma in Europe, adding a fixed-duration, chemotherapy-free immunotherapy option with compelling efficacy and a manageable safety profile for patients whose disease has relapsed after initial treatment.
What This Means for Patients
The approval gives adults with relapsed or refractory follicular lymphoma in Europe access to the first bispecific antibody-based, chemotherapy-free treatment in the second-line setting. Administered as a fixed-duration regimen, it may reduce long-term treatment burden. In the Phase 3 EPCORE FL-1 trial, TEPKINLY plus R2 significantly delayed disease progression and achieved high complete response rates, offering eligible patients a promising new option after their first relapse.
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About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.