Clinical Summary: 

• Design/Population: Subgroup analysis of the phase 3 EPCORE FL-1 trial evaluating fixed-duration epcoritamab plus lenalidomide and rituximab versus rituximab alone in patients with relapsed or refractory follicular lymphoma.
• Key Outcomes: The addition of epcoritamab reduced the risk of progression or death by 79% in the overall study population. Across all evaluated subgroups—including age, comorbidity burden, prior lines of therapy, tumor burden, FLIPI risk score, and POD24 status—hazard ratios consistently ranged between 0.2 and 0.3, demonstrating a uniform progression-free survival benefit.
• Clinical Relevance: These findings indicate that the benefit of epcoritamab plus rituximab extends broadly across both low- and high-risk patient populations and support its use as a new standard treatment option for relapsed or refractory follicular lymphoma.

Benoit Tessoulin, MD, PhD, Nantes University Hospital, Nantes, France, discusses subgroup analyses from the phase 3 EPCORE FL-1 trial evaluating epcoritamab plus lenalidomide and rituximab in patients with relapsed or refractory follicular lymphoma. The primary study previously demonstrated substantial improvements in response rates and progression-free survival with the addition of the CD3×CD20 bispecific antibody epcoritamab to rituximab. 

The subgroup analysis confirmed that the magnitude of benefit was maintained across a wide range of clinically relevant patient populations, including those with high-risk disease features and multiple prior therapies. Safety analyses also demonstrated low discontinuation rates regardless of comorbidity burden, suggesting that the regimen remains feasible and manageable across diverse patient groups.

Dr Tessoulin presented these results at the European Hematological Association (EHA) Annual Meeting in Stockholm, Sweden. 

Transcript: 

I’m Professor Benoit Tessoulin, head of the lymphoma department at Nantes University Hospital, and I would like to present the subgroup analysis from the FL1 trial evaluating epcoritamab plus R² compared with R² alone in patients with relapsed/refractory follicular lymphoma.

As you may be aware, the FL1 trial demonstrated the superiority of epcoritamab plus R² over R² alone in a fixed-duration treatment approach of 12 cycles. The combination increased response rates and significantly improved progression-free survival, with a 79% reduction in the risk of progression or death, corresponding to a hazard ratio of 0.21.

The main objective of this particular analysis was to determine whether patients in different low-risk and high-risk subgroups derived a similar benefit compared with the overall study population.To make a long story short, the answer is yes.

When we looked across a range of patient characteristics—including age, comorbidity burden, number of prior lines of therapy, tumor burden, FLIPI score, POD24 status, and other clinical factors—we found that all patient groups appeared to benefit from the combination. The hazard ratios across these different subgroups generally ranged between 0.2 and 0.3, which is very consistent with the hazard ratio of 0.21 observed in the overall study population.

We also wanted to ensure that the treatment benefit remained manageable across these different patient groups. When we examined adverse events, we found that even among patients with a higher burden of comorbidities, treatment discontinuation rates remained low and did not appear to be associated with the level of comorbidity. In other words, the regimen was generally manageable across all patient populations evaluated.

So overall, these data suggest that epcoritamab plus R² is an effective treatment option across a broad range of patients with relapsed/refractory follicular lymphoma. The benefit appears consistent regardless of baseline risk factors, and the safety profile remains manageable.

Taken together, these findings support epcoritamab plus R² as a new standard treatment option compared with R² alone for patients with relapsed/refractory follicular lymphoma.

Source: 

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 EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-3041.