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 in this setting.

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 Benoît Tessoulin, head of the lymphoma department at Nantes University Hospital, and I will present the subgroup analysis of the FL1 trial with epcoritamab plus R² compared to R² in patients with relapsed or refractory follicular lymphoma.

As you may be aware, the FL1 trial demonstrated the superiority of epcoritamab plus R² compared to R² in a fixed-duration treatment of 12 cycles by increasing the response rate and progression-free survival, with a 79% reduction in the risk of progression or death and a hazard ratio of 0.21. The main analysis we looked at in this particular study was whether patients in different low- or high-risk subgroups had a similar benefit compared with the overall population. 

To make a long story short, yes, all patients benefited from this new combination. When you look at the age of the patient, the burden of comorbidity, the number of prior lines of therapy, the size of the tumor, the FLIPI score, POD24 status, etc and what you see is that all the hazard ratios for those populations and subpopulations lie between 0.2 and 0.3, which is perfectly aligned with the hazard ratio of 0.21 seen in the overall population. 

Just to make sure that the benefit was manageable for all patients, we also looked at the adverse events. What we can see is that even in patients with comorbidities, the rate of treatment discontinuation is pretty low and does not relate to the burden of comorbidity, meaning that the treatment is generally manageable.

So, all in all, this is a good combination for all comers with relapsed or refractory follicular lymphoma and should be considered the standard compared with R². 

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.