Epcoritamab Plus R2 Sustains Efficacy Across Subgroups in R/R Follicular Lymphoma

Epcoritamab (Epkinly) plus lenalidomide and rituximab (R2) produced consistent and durable responses across all clinically relevant patient subgroups in relapsed or refractory (R/R) follicular lymphoma (FL), regardless of comorbidity burden, prior lines of therapy, disease risk, or bulky disease status, according to post-hoc subgroup analyses from the phase 3 EPCORE FL-1 trial presented at the 2026 European Hematology Association Annual Congress.^1,2

In the overall intention-to-treat (ITT) population of 488 randomized patients, epcoritamab plus R2 (n = 243) demonstrated an overall response rate (ORR) of 95% and a complete response rate (CRR) of 83%, compared with 79% and 50%, respectively, with R2 alone (n = 245). The PFS hazard ratio (HR) in the overall ITT population was 0.21 (95% CI, 0.14-0.31), representing a 79% reduction in the risk of disease progression or death.^1,2

The PFS benefit was consistent across all age subgroups. In patients younger than 70 years, the ORR was 96% and CRR was 84% with epcoritamab plus R2 versus 78% and 50% with R2 alone (HR, 0.19; 95% CI, 0.12-0.31). In patients aged 70 years or older, the ORR was 91% and CRR was 79% versus 81% and 50% with R2 alone (HR, 0.29; 95% CI, 0.14-0.60), confirming that older patients derive comparable benefit.^1,2

Comorbidity burden, as assessed by the NHL-5 comorbidity index, did not diminish the epcoritamab benefit. In patients with low NHL-5 scores, the ORR was 94% and CRR was 81% versus 76% and 50% with R2 alone (HR, 0.27; 95% CI, 0.17-0.42). In patients with high or intermediate NHL-5 scores, the PFS HR was 0.14 (95% CI, 0.06-0.29), indicating an even more pronounced benefit in those with greater comorbidity burden.

The benefit was maintained across prior lines of therapy subgroups. In patients with 1 prior line of therapy (LOT), the ORR was 96% and CRR was 87% versus 80% and 53% with R2 alone (HR, 0.20; 95% CI, 0.12-0.34). In patients with 2 or more prior LOTs, the ORR was 94% and CRR was 77% versus 78% and 45% (HR, 0.24; 95% CI, 0.13-0.42).

Baseline Follicular Lymphoma International Prognostic Index (FLIPI) score did not influence the treatment benefit. In patients with FLIPI 0 to 2, the ORR was 96.5% and CRR was 86.6% versus 84.8% and 62.1% with R2 alone (HR, 0.18; 95% CI, 0.10-0.33). In patients with FLIPI 3 to 5, the ORR was 93.0% and CRR was 77.0% versus 72.6% and 35.4% (HR, 0.25; 95% CI, 0.15-0.42).

POD24 status did not influence outcomes. In patients without POD24, the ORR was 96% and CRR was 85.5% versus 85% and 57.6% with R2 alone (HR, 0.17; 95% CI, 0.09-0.32). In patients with POD24, the ORR was 95% and CRR was 80% versus 70% and 39% (HR, 0.22; 95% CI, 0.13-0.37).

The presence of bulky disease or double-refractory status did not negate the PFS benefit. In patients with bulky disease, the ORR was 96% and CRR was 79% versus 62% and 23% with R2 (HR, 0.12; 95% CI, 0.05-0.28), and in non-bulky patients the HR was 0.26 (95% CI, 0.17-0.41). For double-refractory patients, the ORR was 95% and CRR was 79% versus 69% and 35% (HR, 0.23; 95% CI, 0.13-0.39), and for non-double-refractory patients the HR was 0.19 (95% CI, 0.11-0.34).

The lenalidomide RDI analysis confirmed that the PFS benefit was maintained even when dose modifications were required. In patients receiving lenalidomide RDI greater than 70%, the HR was 0.13 (95% CI, 0.06-0.25), and in those receiving RDI of 50% or less, the HR remained 0.28 (95% CI, 0.15-0.51). A comprehensive forest plot confirmed PFS HRs consistently well below 1.0 across all subgroups.

"The EPCORE FL-1 trial, bolstered by this subgroup analysis, established fixed-duration epcoritamab in combination with R2 for relapsed or refractory follicular lymphoma," Benoit Tessoulin, MD, PhD, Nantes University School of Medicine and University Hospital, stated in a news release. "It delivers consistent efficacy and a manageable safety profile, regardless of comorbidity burden."

Safety Profile

The safety profile of epcoritamab plus R2 was generally manageable across all subgroups with no new safety signals.1 Grade ≥3 TEAEs occurred in 89% of patients younger than 70 years and 93% of those aged 70 or older in the epcoritamab arm, versus 64% and 76% with R2 alone. Grade ≥3 TEAEs were similarly high across NHL-5 low and NHL-5 high or intermediate patients (90% in both groups) in the epcoritamab arm. Although neutropenia and infections were more frequent in patients receiving lower lenalidomide doses, the PFS benefit was maintained, consistent with standard practice in which lenalidomide dose reductions are used to manage adverse events while preserving efficacy.1

Study Design and Patient Characteristics

EPCORE FL-1 (NCT05409066) is a global, randomized, open-label, phase 3 trial in adult patients with CD20-positive R/R FL who had received at least 1 prior anti-CD20-based regimen. Patients were randomized 1:1 to epcoritamab 48 mg subcutaneously plus R2 or R2 alone for 12 fixed-duration 28-day cycles. Dual primary endpoints were ORR and PFS by independent review committee. The data cutoff was May 24, 2025, with a median follow-up of 14.8 months.1 Epcoritamab is approved in the United States, Brazil, and China and received a positive CHMP opinion in the EU in May 2026 for this indication.1

"The EPCORE FL-1 subgroup analysis demonstrated consistent and deep responses with a manageable safety profile across all patient characteristics, including varying risk profiles and lenalidomide dosing schedule, which validate the potential of the combination therapy," Judith Klimovsky, MD, Executive Vice President and Chief Development Officer of Genmab, stated in a news release.¹ "These data strongly reinforce our belief that epcoritamab, combined with rituximab and lenalidomide, is poised to transform the treatment paradigm, offering a highly effective and broadly accessible option for relapsed or refractory follicular lymphoma."

References

1. Genmab Presents EPCORE® FL-1 Subgroup Data Demonstrating Consistent Efficacy and Safety Results for Epcoritamab in Combination with Rituximab and Lenalidomide (R2) Across Relapsed or Refractory (R/R) Follicular Lymphoma (FL) Patients. Posted and accessed June 11, 2026. https://sg.finance.yahoo.com/news/genmab-presents-epcore-fl-1-144500106.html

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