As reported in The Lancet by Falchi et al, an interim analysis of the phase III EPCORE FL-1 trial has shown that the addition of the bispecific antibody epcoritamab (for B-cell CD20 and T-cell CD3 antigens) to lenalidomide plus rituximab improved the objective response rate and progression-free survival among patients with relapsed or refractory follicular lymphoma.
Study Details
In the multinational open-label trial, 488 patients were randomly assigned between September 2022 and January 2025 to receive epcoritamab plus lenalidomide-rituximab (n = 243) or lenalidomide-rituximab alone (n = 245). Treatment was given in 28-day cycles for up to 12 cycles: epcoritamab was given subcutaneously at 48 mg weekly in cycles 1 to 3 and every 4 weeks in cycles 4 to 12; lenalidomide was given at 20 mg once daily on days 1 to 21 during cycles 1 to 12 and rituximab was given at 375 mg per m² weekly during cycle 1 (days 1, 8, 15, and 22) and monthly during cycles 2 to 5 (on day 1). The primary endpoints of the analysis were objective response rate and progression-free survival on independent review committee assessment.
Key Findings
Median follow-up at interim analysis was 14.8 months (interquartile range = 11.4–19.0 months).
Objective responses were observed in 231 patients (95%, 95% confidence interval [CI] = 92%–97%) in the epcoritamab group vs 194 patients (79%, 95% CI = 74%–84%) in the control group (P < .0001). Complete response was observed in 83% vs 50% of patients. Median response duration was not evaluable vs 11.5 months; median duration of complete response was not evaluable vs 18.6 months. Among all responders, responses were ongoing at 12 months in 89.2% vs 48.5%.
Median progression-free survival was not reached in the epcoritamab group vs 11.7 months (95% CI = 11.1–15.1 months) in the control group (hazard ratio [HR] = 0.21, 95% CI = 0.14–0.31, P < .0001). Estimated rates at 16 months were 85.5% vs 40.2%.
A total of 92.8% vs 64.9% of patients had not started their next antilymphoma treatment by 16 months (HR = 0.15, 95% CI = 0.09–0.27). Median overall survival was not reached in either group at time of analysis, with the hazard ratio favoring the epcoritamab group (HR = 0.38, 95% CI = 0.18–0.80, P = .0039).
Grade ≥ 3 adverse events occurred in 90% of patients in the epcoritamab group vs 68% of those in the control group. The most common grade ≥ 3 adverse events of special interest in both groups were neutropenia (69% vs 42%) and infections (33% vs 16%). Cytokine-release syndrome (all grade 1 or 2) occurred in 35% of the epcoritamab group and < 1% of the control group. Adverse events led to discontinuation of epcoritamab in 9% of patients, lenalidomide in 19% vs 12%, and rituximab in 3% vs 5%.
The investigators concluded: “Epcoritamab plus [lenalidomide-rituximab] resulted in significantly higher response rate and longer progression-free survival vs [lenalidomide-rituximab] among participants with follicular lymphoma who had received at least one line of therapy. Epcoritamab plus [lenalidomide-rituximab] had more grade 3 or higher adverse events vs [lenalidomide-rituximab]. Adverse events were manageable and consistent with the established safety profiles of the individual components, with no new safety findings identified. These findings position epcoritamab plus [lenalidomide-rituximab] as a new standard of care for second-line or subsequent treatment of follicular lymphoma.”
Franck Morschhauser, MD, of Université de Lille, Centre Hospitalier Universitaire de Lille, Lille, France, is the corresponding author for The Lancet article.
Disclosure: The study was funded by AbbVie and Genmab. For full disclosures of the study authors, visit thelancet.com.
