Long-Term Follow-up Confirms Durable Responses With Epcoritamab in R/R LBCL

Key Clinical Summary

• In heavily pretreated relapsed or refractory large B-cell lymphoma (R/R LBCL) (n = 157), epcoritamab achieved a 59% overall response rate (41% complete response [CR]), with durable responses (median CR duration 36.1 months); 52% of complete responses remained ongoing at 3 years.
• Median overall survival (OS) was 18.5 months overall but not reached in complete responders; 63% of CR patients were alive and 53% progression-free at 3 years. Minimal residual disease (MRD) negativity correlated with improved progression-free survival (PFS).
• Long-term safety was manageable with no new cytokine release syndrome (CRS) or  immune effector cell-associated neurotoxicity syndrome (ICANS) signals; common adverse events (AEs) included CRS (51%), fatigue, and pyrexia, though infections (57%) and treatment discontinuation (17%) remain notable risks.

Epcoritamab monotherapy continues to show durable responses and manageable long-term safety at 3 years in heavily pretreated patients with R/R LBCL, according to study results published in Annals of Hematology.

Diffuse large B-cell lymphoma (DLBCL), the most common LBCL subtype, remains difficult to treat after relapse or refractory disease following initial therapy. Although CAR T-cell therapies have improved outcomes, limitations such as manufacturing delays, eligibility constraints, cost, and toxicity highlight the need for additional immunotherapy options. Epcoritamab, a subcutaneous CD3/CD20 bispecific antibody, redirects T cells to kill malignant B cells and is approved for adults with R/R DLBCL after at least 2 prior lines of therapy.

The authors reported updated 3-year follow-up results evaluating the efficacy and safety of epcoritamab monotherapy in patients with R/R LBCL treated in the expansion cohort of the EPCORE NHL-1 trial. In the overall population of 157 patients, the overall response rate was 59%, including a CR rate of 41% and a partial response rate of 17%. Responses were durable, with a median duration of response of 20.8 months, while the median duration of complete response reached 36.1 months.

At 3 years, an estimated 52% of CRs remained ongoing, and the longest ongoing CR exceeded 43 months. Median PFS was 4.2 months overall, but among patients who achieved complete response, it was 37.3 months, with 53% remaining progression-free at 3 years. Median OS was 18.5 months in the full cohort and was not reached among patients with complete response; an estimated 63% of complete responders were alive at 3 years.

MRD findings also supported the depth of response. Of 119 evaluable patients, 45% became MRD-negative at some point during the study. In a landmark analysis, the 3-year PFS rate was 52% in MRD-negative patients, compared with 18% in MRD-positive patients.

Safety remained consistent with prior reports. Treatment-emergent AEs occurred in 99% of patients and were treatment-related in 85%. The most common events were CRS (51%), fatigue (25%), and pyrexia (25%). No new cases of CRS or ICANS were reported with longer follow-up. Infections occurred in 57% of patients, including grade 3 infections in 24%, grade 4 infections in 2%, and grade 5 infections in 15 patients. Overall, 17% discontinued treatment because of adverse events.

“Long-term results with a 3-year follow-up demonstrate that epcoritamab treatment continued to provide deep and durable responses in patients from the expansion part of the EPCORE NHL-1 trial with heavily pretreated R/R LBCL,” concluded the study authors.

Reference

Karimi YH, Cheah CY, Clausen MR, et al. Efficacy and safety of epcoritamab in relapsed or refractory large B-cell lymphoma: 3-year update from the EPCORE NHL-1 trial. Ann Hematol. 2026;105(3):79. doi:10.1007/s00277-026-06798-4