Fixed-Duration Epcoritamab Plus R2 Shows Strong Outcomes in R/R Follicular Lymphoma
Key Clinical Summary
- Fixed-duration epcoritamab combined with rituximab plus lenalidomide (R2) achieved a 96% overall response rate and 88% complete response (CR) rate in relapsed or refractory (R/R) follicular lymphoma.
- Durable outcomes were observed, with 2-year progression-free survival of 76% and overall survival of 90%.
- Safety was manageable, with mostly low-grade cytokine release syndrome (CRS) and no treatment discontinuations due to CRS.
Introduction
A phase 1b/2 study (EPCORE NHL-2) published in Blood evaluated fixed-duration epcoritamab plus R2 in patients with R/R follicular lymphoma. The combination demonstrated high response rates and durable remissions across risk groups, suggesting a promising chemotherapy-free option for this population.
Study Findings
The EPCORE NHL-2 trial assessed epcoritamab, a subcutaneous CD3×CD20 bispecific antibody, combined with rituximab and lenalidomide in patients with R/R follicular lymphoma after at least 1 prior therapy. A total of 108 patients received treatment, with a median follow-up of 28.2 months.
The primary endpoint—overall response rate—was 96%, with a CR rate of 88%. Notably, high-risk subgroups also demonstrated strong outcomes, including CR rates of 90% in primary refractory disease, 82% in double-refractory disease, and 83% in patients with early progression within 24 months.
Durability of response was substantial. At 2 years, 82% of patients remained in CR, while progression-free survival was 76%, overall survival 90%, and 84% had not initiated subsequent therapy. Minimal residual disease (MRD) negativity was achieved in 86% of evaluable patients using the clonoSEQ assay.
Safety findings showed common treatment-emergent adverse events (TEAEs), including neutropenia (65%), COVID-19 (59%), and CRS (51%). Grade ≥3 TEAEs occurred in 87% of patients, with five grade 5 events attributed to COVID-19. CRS events were predominantly low grade (grade 1-2 in 49% of patients), resolved in all cases, and did not lead to treatment discontinuation.
Clinical Implications
These findings highlight the potential of a fixed-duration, chemotherapy-free regimen in R/R follicular lymphoma, a setting where durable responses remain challenging. The high CR rate and MRD negativity suggest deep remissions, which may translate into prolonged disease control.
Importantly, efficacy was consistent across high-risk subgroups, including patients with early relapse or refractory disease, populations traditionally associated with poor outcomes. The data also suggest a possible advantage when the regimen is used earlier in the treatment sequence, as higher CR rates were observed in second-line compared with later-line settings.
The manageable safety profile further supports clinical feasibility. While CRS was common, it was largely low grade and reversible, aligning with expectations for bispecific antibodies. However, the high rate of infections, including COVID-19–related mortality, underscores the need for vigilant supportive care and infection prevention strategies.
Overall, this regimen may offer a new standard option for patients seeking effective, time-limited therapy without chemotherapy exposure.
The study authors noted that “the combination of epcoritamab and R2 demonstrated clinically meaningful antitumor activity,” with CR rates “higher than any previously published for other bispecific antibody–based regimens in R/R FL.” They also emphasized that responses were observed “across groups of patients with both standard-risk and high-risk disease features,” underscoring broad applicability.
Conclusion
Fixed-duration epcoritamab plus R2 delivers high response rates, durable remissions, and manageable safety in R/R follicular lymphoma. These results support further evaluation and potential earlier use of this chemotherapy-free combination in clinical practice.
Reference
Falchi L, Sureda A, Leppä S, et al. Fixed-duration epcoritamab plus R2 drives favorable outcomes in relapsed or refractory follicular lymphoma. Blood. 2025;146(22):2629-2640. doi:10.1182/blood.2025029909
