Epcoritamab Improves Outcomes, HRQOL in Patients With Relapsed/Refractory Follicular Lymphoma

Patients with relapsed/refractory (R/R) follicular lymphoma reported consistent or increased response rates, survival benefits, and health-related quality of life (HRQOL) when taking epcoritamab in various different forms, as 3 posters presented at the European Hematology Association annual meeting, held in Milan, Italy, from June 12 to 15, 2025, shared new results from studies looking at the efficacy of epcoritamab in this population.

Epcoritamab was found to improve progression-free survival and enhance health-related quality of life in posters presented at the European Hematology Association annual meeting | Image credit: Dr_Microbe - stock.adobe.com

Subcutaneous epcoritamab as a monotherapy has been used as a method of treatment for R/R follicular lymphoma in patients with 2 or more prior lines of therapy based on previous study results. A poster1 reported on the 3-year follow-up of the NHL-3 follicular lymphoma expansion cohorts as well as updating the NHL-1 C1 optimization cohort in patients with follicular lymphoma with at least 2 other lines of therapy.

Participants received epcoritamab every 28 days until either toxicity or the progression of their disease. The NHL-1 cohort consisted of 128 participants, and the NHL-3 cohort consisted of 21 participants, for a total of 149 participants overall. All patients had a high risk of R/R follicular lymphoma. The expansion cohort had a primary end point of efficacy, with minimal residual disease acting as the secondary end point.

The median follow-up time was 35 months in the expansion cohort and 15.5 months in the optimization cohort. The overall response rate (ORR) was 84.6% in the pooled expansion cohort, and the complete response rate (CRR) was 67.1%. Safety was in line with previous reports, as 28% of patients discontinued the medication due to treatment-related adverse events. The optimization cohort had an ORR of 91.9% and a CRR of 73.3%, and 93% of the patients were alive after 3 years. Safety was similar in this cohort, with 11% of the participants discontinuing due to treatment-related adverse events.

Epcoritamab was also tested for efficacy in R/R follicular lymphoma when paired with lenalidomide and rituximab.2 The study aimed to build on results found in the EPCORE NHL-2 trial that found there was efficacy and safety in treating R/R follicular lymphoma with this combination as a means of giving patients an option for treatment that did not involve chemotherapy.

Data from EPCORE NHL-2 Arm 2 were used to compare with the electronic health records from COTA from community and academic centers in the US. Participants received epcoritamab for up to 2 years with the recommended step-up dosing up to 48 mg. The primary outcomes included ORR, CRR, duration of response, duration of complete response, overall survival (OS), and progression-free survival (PFS).

There were 111 patients included in this analysis who were treated with epcoritamab with lenalidomide and rituximab compared with 380 patients who received usual care. Those who took the combination therapy had a 20% higher chance of achieving overall response compared with usual care (96.9% vs 80.5%). They were also 60% more likely to achieve complete response compared with usual care (90.2% vs 55.1%). The risk of progression or death was reduced by 57% in those who took the combination therapy (PFS: HR, 0.43; 95% CI, 0.28-0.68), and the risk of mortality was reduced by 67% (OS: HR, 0.33; 95% CI, 0.16-0.70). Patients also had a 71% reduction in the risk of losing response (HR, 0.29; 95% CI, 0.18-0.47) and a 69% reduction in risk of losing complete response (HR, 0.31; 95% CI, 0.17-0.55) compared with usual care.

Whether epcoritamab taken alone could improve or maintain the HRQOL of the patients taking it for R/R follicular lymphoma, both with and without characteristics that put them at high risk, was also evaluated in a separate study.3

Participants were from the EPCORE NHL-1 study, and patient-reported outcomes were used as a method of evaluation. Participants completed the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) at baseline, cycle 3, cycle 5, cycle 7, cycle 9, and at the end of treatment. Published literature was used to calculate the minimally important differences. Body pain, fever, lack of energy, night sweats, tiredness, and weight loss were all symptoms that could be identified using FACT-Lym, with the mean change from scores at baseline calculated for each participant.

The researchers found that HRQOL was maintained by at least 80% of all participants on epcoritamab based on their total score in the FACT-Lym (range, 80.0%-83.8%) and the Lymphoma Subscale (range, 84.3%-94.6%). The Lymphoma Subscale also recorded numeric improvements in HRQOL in those with symptoms at baseline and improvements in HRQOL in those with 3 or more symptoms at baseline.

All 3 studies have shown that epcoritamab is effective in patients with R/R follicular lymphoma in various combinations and for various purposes. These results back up the continued use of epcoritamab both as a monotherapy and in combination with lenalidomide and rituximab to maintain HRQOL and to improve response and survival in individuals living with R/R follicular lymphoma.

References

1. Vitolo U, Jurczak W, Lugtenburg PJ, et al. Epcoritamab monotherapy demonstrates deep and durable responses at 3-year follow-up in patients with relapsed/refractory follicular lymphoma. Presented at: European Hematology Association 2025; June 12-15, 2025; Milan, Italy. Abstract PF881.

2. Falchi L, Hutchings M, Tybor D, et al. Epcoritamab plus lenalidomide and rituximab achieves high response rates and survival benefits compared with usual care in relapsed/refractory follicular lymphoma: a comparative analysis. Presented at: European Hematology Association 2025; June 12-15, 2025; Milan, Italy. Abstract PF885.

3. Johnson PC, Dueck A, Ghione P, et al. Patient-reported outcomes in patients with relapsed/refractory follicular lymphoma treated with epcoritamab within the entire study cohort and in patients with symptoms at baseline. Presented at: European Hematology Association 2025; June 12-15, 2025; Milan, Italy. Abstract PS1898.