EPCORE FL-1: Epcoritamab Plus Lenalidomide and Rituximab for Follicular Lymphoma
Key Points
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The FDA approved epcoritamab plus lenalidomide and rituximab for relapsed or refractory follicular lymphoma based on the EPCORE FL-1 trial.
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Though the trial data are still maturing, the addition of epcoritamab was associated with improved progression-free survival (PFS) and overall response rate (ORR).
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Cytokine release syndrome (CRS) is a concerning adverse event, but primarily occurs during step-up dosing and is typically low grade.
Epcoritamab Approvals For Follicular Lymphoma
On November 18, 2025, the FDA approved subcutaneous epcoritamab in combination with lenalidomide and rituximab for patients with relapsed or refractory follicular lymphoma, based on the EPCORE FL-1 study. Previously, epcoritamab had accelerated approval as monotherapy for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
Gilles Salles, MD, PhD, of Memorial Sloan Kettering Cancer Center, joined the Oncology Brothers podcast with Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Goasin, MD, of Roswell Park Comprehensive Cancer Center, to discuss the findings from EPCORE FL-1 and how the approval will impact community medical oncologists.
EPCORE FL-1 Trial Design and Efficacy Data
The phase 3 EPCORE FL-1 trial compared epcoritamab plus lenalidomide and rituximab with lenalidomide and rituximab alone. The study enrolled 488 patients with CD20-positive stage II, III, or IV follicular lymphoma that was relapsed or refractory after 1 or more prior regimens including an anti-CD20 monoclonal antibody plus chemotherapy. Epcoritamab was administered with weekly step-up doses in cycle 1, weekly full doses in cycles 2 and 3, and monthly full doses starting in cycle 4 for up to 12 total cycles.
Per the AbbVie press release, median PFS was not reached (NR; 95% CI, 21.0-NR) in the epcoritamab arm compared with 11.2 months (95% CI, 10.5-NR) in the lenalidomide and rituximab arm (hazard ratio, 0.21; 95% CI, 0.13-0.33; P < .0001). Epcoritamab also improved the ORR in the control arm from 74% (95% CI, 68-79) to 89% (95% CI, 84-93; P < 0.0001). The complete response rate was 74% (95% CI, 69-80; P < .0001) with epcoritamab versus 43% (95% CI, 37-50) with lenalidomide and rituximab.
While the addition of epcoritamab makes the treatment more demanding, particularly in the first 3 cycles, the HR for median PFS is suggestive of a prolonged benefit once the fixed-duration therapy is complete. “After 1 year, [patients] may experience longer treatment-free intervals, which is important for the quality of life of our patients,” said Dr. Salles.
EPCORE FL-1 Safety Data
The most common adverse events, occurring in 20% or more of patients who received epcoritamab, included rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, CRS, pneumonia, COVID-19, and fever. The most common grade 3 or 4 laboratory abnormalities occurring in 10% or more of patients were decreased neutrophil, lymphocyte, and platelet counts. One case of grade 1 immune effector cell-associated neurotoxicity syndrome was reported.
CRS events occurred in 24% of patients at the step-up dosage schedule, and were primarily grade 1 (19%) or grade 2 (5%). Since CRS with bispecifics occurs shortly after drug administration, Dr. Salles recommended calling patients the following day and having them take dexamethasone if they feel feverish or unwell. In his experience, most CRS events occur in the first cycle and are resolved within a few days.
If epcoritamab doses are delayed by more than 2 weeks during the step-up schedule, treatment should restart at the previous dose level rather than the next intended step up. Dr. Salles noted that, “the longer the [delay] is, the better you go back to a lower dose to make sure the patients tolerate well.”
Overall, “I think what we can offer to the patient is a treatment that gives them a long treatment-free interval,” said Dr. Salles.