Odronextamab Shows Durable Response in Relapsed Follicular Lymphoma

Odronextamab is a safe and effective treatment for patients with relapsed or refractory follicular lymphoma (FL), according to two-year follow-up results of the ELM-2 trial presented at the 2025 American Society of Clinical Society Annual Meeting by Deepa Jagadeesh, MD, of the Cleveland Clinic.

A total of 157 patients received intravenous odronextamab, an investigational off-the-shelf CD20×CD3 bispecific antibody, for a median of 19 cycles until disease progression or unacceptable toxicity. Cycle 1 step-up dosing was implemented to reduce the risk for cytokine release syndrome (CRS). Patients who maintained a complete response (CR) for at least nine months switched from maintenance dosing once every two weeks to once every four weeks.

The primary endpoint was the objective response rate (ORR). Secondary endpoints were CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of 128 efficacy-evaluable patients, the ORR was 80.5% and the CR rate was 74.2% at a median follow-up of 28.3 months. The median DOR was 26.0 months, with a median duration of CR of 32.2 months. Among high-risk subgroups, the ORR was 78.4% for patients with a Follicular Lymphoma International Prognostic Index score of 3–5 and 81.0% for patients who had disease progression within two years of frontline therapy.

The median PFS and OS were 23.0 months and 54.2 months, respectively. Patients who were measurable residual disease (MRD) negative at week 12 had a longer PFS (42.4 months) than patients who were MRD positive (21.6 months) at week 12.

As for safety, all 157 patients experienced treatment-emergent adverse events (TEAEs), with 86.0% being grade 3 or higher. Treatment discontinuation from TEAEs, most commonly COVID-19, occurred in 15.3% of patients.

With 0.7/4/20 mg step-up dosing, 46.1% of patients experienced grade 1 CRS, 13.5% experienced grade 2 CRS, and one patient experienced grade 3 CRS. One patient experienced grade 2 immune effector cell-associated neurotoxicity syndrome and 79.0% of patients experienced an infection, most commonly COVID-19 in 38.2% of patients.

“With longer follow-up, odronextamab demonstrated durable responses in heavily pretreated pts with R/R FL from ELM-2, with robust efficacy in those with high-risk features, and a generally manageable safety profile,” Dr. Jagadeesh and colleagues wrote. “Overall, these compelling results support odronextamab as a potential off-the-shelf treatment option for pts with R/R FL.”