Fixed-Duration Epcoritamab Combo Shows Superiority in Follicular Lymphoma

The addition of fixed-duration epcoritamab-bysp (Epkinly) to lenalidomide (Revlimid) and rituximab (Rituxan) exhibited superior outcomes vs lenalidomide/rituximab alone across key subgroups as a treatment for patients with relapsed/refractory follicular lymphoma (FL) previously treated with at least 1 prior therapy, including an anti-CD20 monoclonal antibody plus an alkylating agent, according to findings from a subgroup analysis of the phase 3 EPCORE FL-1 trial (NCT05409066) presented at the European Hematology Association (EHA) 2026 Congress.

Efficacy data from the analysis revealed that the epcoritamab regimen elicited an objective response rate (ORR) of 95% vs 79% with the control regimen, with a complete response (CR) rate of 83% vs 50%, respectively. Moreover, the progression-free survival (PFS) outcomes favored the investigational arm (HR, 0.21; 95% CI, 0.14-0.31).

Moreover, a subgroup analysis for age revealed that the efficacy benefit was maintained across patient subgroups. Among patients younger than 70 years of age, the ORR was 96% vs 78% in the investigational and control groups, respectively, with a CR rate of 84% vs 50%. The HR for PFS was 0.19 (95% CI, 0.12-0.31). Additionally, among those 70 and older, the ORR was 91% vs 81%, the CR rate was 79% vs 50%, and the HR for PFS was 0.29 (95% CI, 0.14-0.60).

Additionally, among patients with a low non-Hodgkin lymphoma comorbidity score (NHL-5), the ORR was 94% vs 76% in the epcoritamab and control arms, with a CR rate of 81% vs 50% and an HR for PFS of 0.27 (95% CI, 0.17-0.42). For patients with intermediate or high NHL-5, the ORR was 97% vs 84%, the CR rate was 86% vs 49%, and the HR for PFS was 0.14 (95% CI, 0.06-0.29).

Furthermore, epcoritamab conferred superior outcomes regardless of prior lines of therapy (LOTs). Among patients who received 1 prior LOT in the investigational and control arm, the ORR was 96% vs 80%, the CR rate was 87% vs 53%, and the HR for PFS was 0.20 (95% CI, 0.12-0.34). For those treated with at least 2 prior LOTs, the ORR was 94% vs 78%, respectively; the CR rate was 77% vs 45%, and the HR for PFS was 0.24 (95% CI, 0.13-0.42).

Finally, patients benefitted with epcoritamab regardless of Follicular Lymphoma International Prognostic Index (FLIPI) score. Among those with a FLIPI score of 0 to 2 treated in the investigational and control arms, the ORR was 96% vs 85%, the CR rate was 87% vs 62%, and the HR for PFS was 0.18 (95% CI, 0.10-0.33). For those with a FLIPI score of 3 to 5, the ORR was 93% vs 73%, the CR rate was 77% vs 35%, and the HR for PFS was 0.25 (95% CI, 0.15-0.42).

“Fixed-duration epcoritamab plus [lenalidomide and rituximab] was superior to [lenalidomide and rituximab alone] in the EPCORE FL-1 study [among] patients with FL in the [second-line setting or later],” Benoit Tessoulin, MD, PhD, of the Nantes University School of Medicine and University Hospital, as well as a member of the European Mantle Cell Lymphoma Network, stated in the presentation. “There was a 79% reduction in the risk of disease progression or death. The [epcoritamab combination] led to sustained, improved efficacy with manageable safety across clinically relevant subgroups, consistent with the findings in the overall population.”

In the phase 3 EPCORE-FL 1 protocol, patients with histologically confirmed CD20-positive relapsed/refractory FL were randomly assigned 1:1 to receive rituximab and lenalidomide with or without epcoritamab. Epcoritamab was initially given as 3 weekly step-up doses during cycle 1, followed by weekly at a consistent dose for cycles 2 and 3, and then every 4 weeks from cycles 4 to 12. Rituximab was administered at a dose of 375 mg/m² for 5 cycles, at a weekly schedule for cycle 1, and then every 4 weeks for cycles 2 to 5. Lenalidomide was given at 20 mg daily for twelve 21-day cycles.

The dual primary end points of the study included ORR and PFS, both per independent review committee (IRC) assessment. Secondary end points included CR rate per IRC assessment, overall survival, and safety.

Among patients younger than 70, treatment-emergent adverse effects (TEAEs) deemed grade 3 or higher, serious, or fatal occurred in 89% vs 64%, 54% vs 27%, and 1% vs 4% of the investigational and control arms. Moreover, TEAEs leading to discontinuation of treatment occurred in 15% vs 10%. In the 70 and older subgroup, the rates for grade 3 or higher, serious, or fatal TEAEs were 93% vs 76%, 60% vs 35%, and 7% vs 8%. TEAEs leading to discontinuation of therapy occurred in 31% vs 17% of each.

Furthermore, among patients with NHL-5–low disease, the rates for grade 3 or higher, serious, or fatal TEAEs in the epcoritamab and control arms were 90% vs 67%, 55% vs 24%, and 2% vs 5%. TEAEs leading to treatment discontinuation occurred in 17% vs 10%, respectively. Finally, for those with NHL-5–intermediate or high disease, the rates for grade 3 or higher, serious, or fatal TEAEs were 90% vs 69%, 56% vs 37%, and 4% vs 5%. Moreover, TEAEs leading to dose discontinuations occurred in 22% vs 15% of the respective groups.

Disclosures: Tessoulin received honoraria from AbbVie, AstraZeneca, Incyte, BMS, Eli Lilly, and Johnson & Johnson.

Reference

Nijland M, Falchi L, Linton K, et al. Clinically relevant subgroup analysis from the randomized phase 3 EPCORE FL-1 trial: treatment (tx) effect of epcoritamab with lenalidomide and rituximab (R²) IN R/R follicular lymphoma (FL). Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S229.