Epcoritamab Plus Lenalidomide/Rituximab Win EU Approval for R/R Follicular Lymphoma

The European Commission has granted marketing authorization for epcoritamab (Tepkinly) plus lenalidomide (Revlimid) and rituximab (Rituxan) for the treatment of adult patients with relapsed or refractory follicular lymphoma.¹

The approval was supported by results from the phase 3 EPCORE FL-1 trial (NCT05409066), in which fixed-duration epcoritamab plus lenalidomide and rituximab (n = 243) reduced the risk of disease progression or death by 79% compared with lenalidomide plus rituximab alone (n = 245; HR, 0.21; 95% CI, 0.13-0.33; P < .0001).

The epcoritamab-based combination also produced an overall response rate (ORR) of 96% (95% CI, 90.2%-98.6%) compared with 81% (95% CI, 72.7%-87.7%) with lenalidomide/rituximab alone (P < .0001). Complete response (CR) was achieved by 74% (95% CI, 68.5%-79.8%) of patients who received epcoritamab plus lenalidomide and rituximab vs 43% (95% CI, 37.0%-49.7%) of those who received lenalidomide and rituximab alone.

"Follicular lymphoma is a persistent form of cancer that remains incurable, which means patients need more treatment options. Patients often relapse and experience shorter remissions and have fewer treatment options each time the disease returns," Catherine Thieblemont, MD, PhD, head of the hemato-oncology department, Paris Cité University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris, stated in a news release. "The results shown in the EPCORE FL-1 trial are clinically meaningful, demonstrating the potential for epcoritamab plus lenalidomide and rituximab to change the treatment paradigm for patients, offering the chance at a durable response with a chemotherapy-free option."

The regulatory decision follows the November 2025 FDA approval of epcoritamab in combination with lenalidomide and rituximab for patients with relapsed or refractory follicular lymphoma, which was also based on data from EPCORE FL-1.²

How was the EPCORE FL-1 trial designed?

EPCORE FL-1 was a phase 3, open-label, randomized trial that enrolled patients at least 18 years of age with follicular lymphoma who had received at least one prior line of systemic therapy containing an anti-CD20 monoclonal antibody in combination with chemotherapy.³ Patients also needed to have an ECOG performance status of 2 or less and an estimated creatinine clearance higher than 50 mL/min.

If patients were refractory to lenalidomide or had lenalidomide exposure 12 months prior to randomization, they were not enrolled in the trial.

Patients were randomly assigned to the epcoritamab-based regimen or lenalidomide plus rituximab alone.¹

Epcoritamab was administered in 28-day cycles for up to 12 cycles or until disease progression or unacceptable toxicity.

The dual primary end points were progression-free survival and ORR as determined by Lugano 2014 criteria and assessed by an independent review committee; CR rate and duration of response served as additional efficacy outcome measures.

What is the safety profile of epcoritamab plus rituximab/lenalidomide?

The safety profile of epcoritamab plus lenalidomide and rituximab in EPCORE FL-1 was consistent with the known safety profiles of the individual agents.

The most common any-grade adverse effects (AEs) that occurred in at least 20% of patients were neutropenia, rash, upper respiratory tract infections, fatigue, diarrhea, injection site reactions, anemia, constipation, thrombocytopenia, cytokine release syndrome (CRS), hypogammaglobulinemia, COVID-19, pyrexia, and pneumonia.

Serious AEs were experienced by 44% of patients who received the triplet; those reported in at least 5% of patients included CRS, pneumonia, COVID-19, and febrile neutropenia.

References

1. AbbVie announces TEPKINLY (epcoritamab) in combination with lenalidomide and rituximab is approved by the European Commission for the treatment of relapsed or refractory follicular lymphoma. News release. AbbVie. July 6, 2026. Accessed July 6, 2026. https://news.abbvie.com/2026-07-06-AbbVie-Announces-TEPKINLY-R-epcoritamab-in-Combination-with-Lenalidomide-and-Rituximab-is-Approved-by-the-European-Commission-for-the-Treatment-of-Relapsed-or-Refractory-Follicular-Lymphoma
2. FDA approves epcoritamab-bysp for follicular lymphoma indications. FDA. November 18, 2025. Accessed July 6, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-epcoritamab-bysp-follicular-lymphoma-indications
3. 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. Updated July 28, 2025. Accessed July 6, 2026. https://clinicaltrials.gov/study/NCT05409066