Epcoritamab Expands Treatment Options in Relapsed or Refractory Follicular Lymphoma

Key Summary

• Epcoritamab monotherapy produced an overall response rate of 82% and a complete response rate of 62.5% in heavily pretreated relapsed or refractory follicular lymphoma (R/R FL) in the phase 1/2 EPCORE NHL-1 study.
• In a cycle 1 optimization cohort, cytokine release syndrome fell from 66% to 49%, with no grade 3 or higher events and no immune effector cell–associated neurotoxicity syndrome reported.
• Subcutaneous administration, outpatient feasibility, and comparable efficacy to other CD20×CD3 bispecific antibodies may make epcoritamab an attractive option in selected patients.

Epcoritamab is emerging as an important chemotherapy-free option in FL, according to an editorial commentary reviewing results from the EPCORE NHL-1 trial and the evolving role of CD20×CD3 bispecific antibodies in this setting. The discussion highlights epcoritamab’s activity in high-risk patients and its potential relevance for treatment sequencing, safety, and health care resource use.

Main News

FL remains incurable in advanced stages despite therapeutic advances, and outcomes are particularly poor for patients with progression of disease within 24 months of first-line treatment or multiply relapsed disease. In EPCORE NHL-1, epcoritamab was evaluated in patients with grade 1-3A FL who had received at least 2 prior lines of therapy, including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide.

The pivotal cohort enrolled 128 patients. Median age was 65 years, 60% had stage IV disease, 54% had primary refractory disease, 42% had progression of disease within 24 months after first-line chemoimmunotherapy, and 31% had received 4 or more prior lines of therapy. Five percent had prior chimeric antigen receptor (CAR) T-cell therapy exposure.

Overall response rate was 82%, and 62.5% achieved complete response. Median time to response was 1.4 months. At a median follow-up of 17.4 months, 49.4% remained progression-free at 18 months, including 73.8% of those with complete response, and 70.2% were alive. Measurable residual disease negativity was observed in 61 of 91 evaluable patients and was associated with improved progression-free survival.

Safety findings showed cytokine release syndrome in 66% of the pivotal cohort, nearly all grade 1-2, with only 2 grade 3 events. Immune effector cell–associated neurotoxicity syndrome was reported in 6%, all low grade. In the cycle 1 optimization cohort of 86 patients, cytokine release syndrome decreased to 49%, with no grade 3 or higher events and no immune effector cell–associated neurotoxicity syndrome.

Clinical Implications

For managed care and oncology stakeholders, epcoritamab’s profile raises several practical considerations. Its subcutaneous administration may be more convenient than intravenous bispecific antibodies and may reduce infusion-related logistics and resource use. The cycle 1 optimization approach also removed the need for hospitalization, supporting broader outpatient delivery.

The editorial notes that efficacy and safety appear broadly comparable across available CD20×CD3 bispecific antibodies, including mosunetuzumab, glofitamab, and odronextamab, though cross-trial comparisons remain limited by differences in patient populations and trial design. In this environment, factors such as route of administration, treatment duration, supportive care requirements, and cost may increasingly influence treatment selection.

The commentary also frames epcoritamab within a broader sequencing debate with CAR T-cell therapies. Bispecific antibodies may be favored in older or frailer patients because of lower rates of high-grade cytokine release syndrome and neurotoxicity, easier access, and administration outside specialized centers.

Conclusion

Epcoritamab adds another active bispecific antibody option for FL and may offer meaningful clinical and operational advantages in selected patients. As additional combinations and earlier-line studies mature, its role in sequencing and long-term management will become clearer.

Reference

Bouziana S, Patten Piers PEM. Epcoritamab: the next frontier in the treatment of relapsed/refractory follicular lymphoma. AME Clin Trials Rev. 2025;3(1):54. doi:10.21037/actr-24-264