Fixed-Duration Epcoritamab Plus R2 Produces High Response Rates and Favorable Outcomes for R/R Follicular Lymphoma
Fixed-duration epcoritamab in combination with rituximab and lenalidomide (R2) provided deep and durable responses among patients with relapsed/refractory (R/R ) follicular lymphoma (FL), including those with high-risk disease features, according to updated results from arm 2 of the EPCORE NHL-2 trial, published in Blood.
Previous research has demonstrated efficacy for epcoritamab for the treatment of heavily pretreated R/R FL. Researchers conducted a phase 1b/2 open-label, multicenter trial to determine the efficacy of fixed-duration epcoritamab, up to 2 years, in addition to rituximab and lenalidomide after at least 1 line of prior therapy.
The primary end point was overall response rate (ORR), with secondary end points including complete response (CR) rate, duration of response (DOR), duration of complete response (DOCR), time to response, time to next therapy, progression-free survival (PFS), overall survival (OS), minimal residual disease (MRD) negativity, and safety.
Overall, 108 patients were treated with subcutaneous epcoritamab (48 mg following step-up dosing) administered for up to 2 years alongside rituximab and lenalidomide for up to 12 28-day cycles. The median age was 65 years, and the median prior lines of therapy was 1 (range, 1 to 7).
The median follow-up was 28.2 months (range, 2.4 to 39.0; 95% confidence interval [CI], 27.9 to 30.0). At follow-up 50% of patients discontinued treatment, including 24% due to adverse events and 16% due to progressive disease. The median duration of treatment with epcoritamab was 22 months (range, 0 to 26).
The ORR was 96% (95% CI 91 to 99), with a CR rate of 88% (95% CI, 80 to 93). CR rates remained high among patients identified as high-risk which were those with primary refractory disease (90%), those with disease progression within 24 months of first-line therapy (POD24; 89%) and those with more than 1 prior line of therapy (83%). The median time to response was 1.4 months (range, 1.0 to 3.1) and the median time to CR was 1.4 months (range, 1.0 to 8.4). The median DOR and DOCR was 26.2 months and the median PFS was slightly longer at 27.6 months. Additionally, the median OS was 28.2 months and 28.0 months until next therapy.
Estimated 2-year outcome estimates for remaining in CR was 82% (95% CI, 72 to 89), PFS was 76% (95% CI, 65 to 83), 90% (95% CI, 83 to 95) for OS, and 84% (95% CI, 75 to 90) for time to next therapy. Minimal residual disease (MRD) negativity was achieved in 86% of evaluable patients, supporting the depth of response.
In terms of safety, treatment-emergent adverse events were neutropenia (65%), COVID-19 infection (59%), and cytokine release syndrome (CRS; 51%). Grade ≥3 treatment-emergent adverse events occurred in 87% of patients.
The researchers concluded, “With more than 2 years of follow-up, fixed-duration epcoritamab plus R2 demonstrated highly encouraging results, with deep and durable responses observed across all patient populations treated, including patients with high-risk disease features.”
They added, “The high MRD-negativity rates further substantiate the depth of responses achieved with this potent regimen.”
Source:
Falchi L, Sureda A, Sirpa Leppä, et al. Fixed-Duration Epcoritamab Plus R2 Drives Favorable Outcomes in Relapsed or Refractory Follicular Lymphoma. Blood. Published online September 8, 2025. doi:10.1182/blood.2025029909
