Epcoritamab in combination with rituximab and lenalidomide has the potential to be the new standard of care in patients with second-line follicular lymphoma, according to results from the phase 3 EPCORE-FL-1 trial.
The results were presented during an oral abstract session at the American Society of Hematology Annual Meeting and Exposition in Orlando, Florida, by Lorenzo Falchi, MD, a lymphoma specialist at Memorial Sloan Kettering Cancer Center in New York.
“E+R² [epcoritamab plus rituximab and lenalidomide] sets a new benchmark as a readily available treatment, is suitable for outpatient administration, and has the potential to become a new standard of care in 2L+ FL,” the authors wrote in the abstract.
The phase 3 EPCORE-FL-1 trial evaluated the safety and efficacy of epcoritamab, a CD20xCD3 bispecific antibody, in combination with rituximab and lenalidomide compared to rituximab and lenalidomide alone in patients with relapsed or refractory follicular lymphoma. To be enrolled, eligible patients had to be 18 years and older, have an ECOG performance status 0–2, be eligible to be treated with rituximab plus lenalidomide, and have relapsed or refractory disease after ≥1 prior anti-CD20–based chemoimmunotherapy regimen and the other following characteristics:
- FDG-PET–positive disease with at least one measurable nodal (≥1.5 cm) or extranodal lesion (≥1.0 cm) on CT or MRI.
- Histologically confirmed classic follicular lymphoma (grade 1–3a), stage II–IV, CD20-positive, with no transformation to aggressive lymphoma.
- Adequate renal function (creatinine clearance ≥50 mL/min).
In the presented abstract, Dr. Falchi and colleagues reported that as of the data cut-off date, 488 patients who received the treatment had clear and clinically meaningful improvements over R² alone. Patients receiving the combination had higher response and complete response rates, more durable responses, and a longer progression-free survival, translating to an approximately 80% reduction in the risk of disease progression or death. These benefits were consistent across key high-risk subgroups. The safety profile was manageable, with mostly low-grade cytokine release syndrome and infrequent neurologic events, though higher rates of cytopenias and infections were observed with the combination, the investigators reported.
“[Epcoritamab] is the first CD20xCD3 bispecific antibody to demonstrate clinical benefit over standard of care in a randomized phase 3 trial in patients with FL, with statistically significant improvements in ORR, CR rate, and a 79% reduction in the risk of progression or death,” the authors wrote.
Reference
Falchi L, Nijland M, Huang H. Primary phase 3 results from the EPCORE FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma. Abstract #466. Presented at the 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, Florida.
