Epcoritamab Plus R2 Achieves 88% Complete Response and 86% MRD Negativity in Relapsed Follicular Lymphoma
In the EPCORE NHL-2 expansion cohort, 108 patients with relapsed/refractory follicular lymphoma received fixed-duration epcoritamab plus rituximab-lenalidomide. The overall response rate was 96% with 88% complete responses, and MRD negativity by clonoSEQ was achieved in 86% of evaluable patients. Two-year estimates for remaining in CR and PFS were 82% and 76% respectively, with manageable toxicity including mostly low-grade cytokine release syndrome.
The original study
Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma.
- Authors
- Falchi L, Sureda A, Leppä S, Vermaat JSP, Nijland M, Christensen JH, et al.
- Journal
- Blood
- Type
- Journal Article, Clinical Trial, Phase II, Clinical Trial, Phase I, Multicenter Study
- PMID
- 40920572
Original abstract
Epcoritamab is a subcutaneous CD3×CD20 bispecific antibody approved as monotherapy for relapsed/refractory (R/R) follicular lymphoma (FL). We evaluated fixed-duration epcoritamab with rituximab plus lenalidomide (R2) in R/R FL in arm 2 of EPCORE NHL-2 (phase 1b/2). Patients received epcoritamab (2 step-up doses, then 48-mg full doses) for up to 2 years, and R2 for up to 12 cycles (28 days per cycle). The primary end point was overall response rate (ORR) per investigator assessment (Lugano criteria). As of 21 September 2024, 108 patients received ≥1 epcoritamab dose in expansion (median follow-up, 28.2 months). Median age was 65 years; 57% had 1 previous line of therapy. ORR and complete response (CR) rate were 96% and 88%, respectively; CR rates in patients with high-risk features were 90% (primary refractory), 82% (refractory to anti-CD20 and an alkylating agent), and 83% (disease progression within 24 months of first-line therapy). Two-year estimates for remaining in CR, progression-free survival, overall survival, and not starting next antilymphoma therapy were 82%, 76%, 90%, and 84%, respectively. Minimal residual disease negativity was observed in 86% of evaluable patients (clonoSEQ assay). Common treatment-emergent adverse events (TEAEs) included neutropenia (65%), COVID-19 (59%), and cytokine release syndrome (CRS; 51%). Grade ≥3 TEAEs occurred in 87% of patients; 5 had grade 5 TEAEs (all COVID-19). CRS events were mostly low grade (grade 1, 38%; grade 2, 11%; grade 3, 2%), all resolved, and none led to epcoritamab discontinuation. Fixed-duration epcoritamab plus R2 demonstrated deep, durable responses with manageable safety and favorable outcomes in R/R FL, irrespective of risk features. This trial was registered at www.ClinicalTrials.gov as #NCT04663347.