Epcoritamab Triplet Shows ‘Deep, Durable Responses’ in Follicular Lymphoma in Two-Year Follow-Up

Fixed-duration epcoritamab with rituximab plus lenalidomide (R²) drives deep and durable responses in patients with relapsed or refractory follicular lymphoma (FL), according to results from the two-year follow-up of the EPCORE NHL-2 trial presented at the 66^th American Society of Hematology Annual Meeting & Exposition.

While R² is an accepted regimen based on the AUGMENT trial, “there exists a clear need for improvement of outcomes, especially for [patients] with high-risk features, including disease progression within 24 months of first-line chemoimmunotherapy or primary/double-refractory disease, for whom there is no established standard of care,” the researchers wrote.

In EPCORE NHL-2, subcutaneous epcoritamab was administered in a two-step step-up-dosing regimen at 0.16 mg and 0.8 mg in cycle 1. For up to two years, patients also received full doses of 48 mg at one of two dosing frequencies:

• Arm 2a: 48 mg once a week (QW) in cycles 1-3, Q2W in cycles 4-9, and Q4W in cycles 10 and beyond
• Atm 2b: 48 mg QW in cycles 1-2 and Q4W in cycles 3 and beyond

Of the 111 patients, most (61%) had stage IV disease. Of the 57% who had one line of prior treatment, most received alkylating agents (93%) and anthracyclines (64%), while 3% received chimeric antigen receptor T-cell therapy.

At a median follow-up of 25.3 months, the overall response rate (ORR) was 96% and the complete response (CR) rate was 87%. CR rates were comparable among those with high-risk features versus those without.

The researchers also performed measurable residual disease (MRD) analysis on peripheral blood mononuclear cell samples using clonoSEQ® assay. Of 73 evaluable patients, 64 (88%) achieved MRD negativity.

The researchers noted that most patients were enrolled and treated during the COVID-19 pandemic. Fifty-seven percent of patients experienced COVID-19, which led to epcoritamab discontinuation in 11% of patients. Other treatment-emergent adverse events (TEAEs) included neutropenia (62%) and cytokine release syndrome (CRS; 51%). However, the researchers noted that CRS events were low grade with the two-step dosing regimen. Grade 1 immune effector cell-associated neurotoxicity syndrome, which occurred in one patient, was resolved.

“With more than [two years] of follow-up, fixed-duration epcoritamab [plus] R² continued to show deep and durable responses,” the researchers concluded. “Considering limitations of cross-trial comparisons, these results (estimated [two-year progression-free survival], 70%) compare favorably with those reported for R² alone in the AUGMENT trial.”

The ongoing, randomized phase III EPCORE FL-1 trial will further evaluate this triplet treatment regimen.

Reference

Falchi L, Balari AS, Leppä L, et al. “Fixed-duration epcoritamab + R2 drives deep and durable responses in patients with relapsed or refractory follicular lymphoma: 2-year follow-up from arm 2 of the epcore NHL-2 trial.” Abstract #342. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.