At the American Society of Hematology (ASH) 2025 meeting, updated results from the phase 2 EPCORE NHL‑2 (NCT04663347) trial highlighted the potential of epcoritamab combined wiht chemotherapy to improve outcomes for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), spanning both high-risk and frail or older populations.
Updated results highlight the promise of epcoritamab combined with chemotherapy for newly diagnosed DLBCL. | Image credit: LASZLO – stock.adobe.com
Epcoritamab Combination Therapy Shows Promise in Newly Diagnosed Diffuse Large B-Cell Lymphoma
Epcoritamab, a novel T-cell engaging bispecific antibody, is demonstrating notable efficacy and manageable safety when combined with chemotherapy for the treatment of newly diagnosed diffuse large B-cell lymphoma (DLBCL), particularly in patients with high-risk features. Recent data presented at the American Society of Hematology (ASH) 2025 conference from the EPCORE NHL-2 trial highlight promising outcomes with two different epcoritamab-based regimens.
Epcoritamab Plus R-mini-CHOP
The first analysis investigated epcoritamab in combination with a reduced-intensity R-mini-CHOP regimen. This approach resulted in extraordinary 2-year remission rates and high rates of minimal residual disease (MRD) negativity. Overall survival (OS) was 76% and 82%, respectively. Notably, 95% of evaluable patients achieved MRD negativity, even among those with high International Prognostic Index (IPI) scores (3-5) and bulky disease. Moreover, 86% of patients who were MRD-negative at cycle 3 day 1 (C3D1) maintained this negativity through cycle 6 day 1 (C6D1). However, treatment-related adverse events, specifically grade 3 or greater infections, occurred in 29% of patients, leading to 11% discontinuing epcoritamab.
Epcoritamab Plus R-CHOP
A second analysis evaluated a fixed-duration epcoritamab regimen combined with six cycles of standard R-CHOP chemotherapy,followed by up to one year of epcoritamab monotherapy. Epcoritamab was administered subcutaneously with a step-up dosing schedule in the first cycle, then weekly for cycles 1-4, every three weeks for cycles 5-6, and subsequently monthly as monotherapy.
In this arm of the EPCORE NHL-2 trial,47 patients with a median age of 64 received the combination. A high proportion of patients (57%) had an IPI score of 3, while 38% had scores of 4-5, indicating a high-risk group. after a median follow-up of 38.8 months, the overall response rate (ORR) was 98%, with a complete response (CR) rate of 85%. Importantly, 67% of responses and 75% of CRs remained ongoing at 33 months. [1]
High CR rates were observed consistently across different subgroups, including patients with IPI scores of 3 (86%) and 4-5 (83%), as well as varying ages and tumor characteristics. MRD negativity was achieved in 86% of evaluable patients by cycle 3 day 1, with sustained reductions in circulating tumor DNA (ctDNA) through cycle 6 day 1. A significant majority of patients (94%) completed all six cycles of R-CHOP, and 68% completed the planned treatment course.Among those who completed treatment, 30 of 32 patients achieved a CR, with 87% maintaining their response at a median follow-up of 25.3 months. [2]
The safety profile in this cohort was consistent with previous reports,with serious or grade 3 or greater infections occurring primarily during the first six months of treatment. No new grade 5 events (death related to treatment) were reported.
Implications for DLBCL Treatment
These findings suggest that epcoritamab-based combination therapies represent a promising new approach for the treatment of newly diagnosed DLBCL,particularly for patients with high-risk features. The high rates of MRD negativity and durable remissions observed in the EPCORE NHL-2 trial warrant further examination and may lead to improved outcomes for patients with this aggressive lymphoma.
References:
- Cheah C, Belada D, Darrah J, et al. Epcoritamab plus R-mini-CHOP results in 2-year remmissions and high MRD negativity rates in elderly patients with newly diagnosed DLBCL: Results from the EPCORE NHL-2 trial. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida. Poster 64.
- Falchi L, de Vos S, Brody J, et al.Fixed-duration epcoritamab plus R-CHOP in patients with newly diagnosed DLBCL and high IPI scores (3-5) led to sustained remissions and disease-free survival beyond 3 years: Results from the EPCORE NHL-2 trial. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida.Poster 1955.
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