Odronextamab Demonstrates Durable Responses, Manageable Safety Among Patients With Heavily Pretreated R/R Follicular Lymphoma

According to results from the ELM-2 study, odronextamab treatment achieved high complete response rates among heavily pretreated patients with relapsed/refractory (R/R) follicular lymphoma (FL), while demonstrating a manageable safety profile.

“Odronextamab, a [CD20-CD3] bispecific antibody that engages cytotoxic T-cells to destroy malignant B-cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL),” stated lead study author Tae Min Kim, MS, PhD, Seoul National University Cancer Research Institute, Seoul, South Korea, and colleagues.

This phase 2 trial examined odronextamab among patients with R/R FL following 2 or more lines of systemic therapy. Investigators noted the primary end point was objective response rate (ORR) by independent central review, and secondary end points included ORR per local investigator assessment, complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), patient-reported outcomes (PROs), and pharmacokinetics. Study participants received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help moderate the risk of cytokine release syndrome (CRS), until either disease progression or unacceptable toxicity.

At the data cutoff, 128 eligible patients with R/R FL had enrolled at 49 sites between December 18, 2019, and July 27, 2022. Trial participants completed a median of 19.4 treatment cycles, with 95% completing cycle 1 and 85% completing 4 or more cycles. It was noted that 29 patients (23%) remained on treatment at the time of data cut-off.

Results demonstrated that at the 20.1 months’ efficacy follow-up, the ORR was 80% and CR rate was 73.4%. Additionally, the median duration of CR was 25.1 months, and the median PFS was 20.7 months. It was noted the median OS was not reached.

The safety profile showed the most common reasons for treatment discontinuation were disease progression (25%), adverse events (16%), death (all due to adverse events), physician decision, and patient withdrawal (each 10%). The most common treatment-related adverse events were cytokine release syndrome [56%; grade ≥ 3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%).

“In this study, odronextamab treatment achieved deep and durable responses in heavily pretreated patients with R/R FL and demonstrated a generally manageable safety profile,” concluded Dr Kim and colleagues.

“These data are consistent with those from patients with R/R FL in the ELM-1 study and with results reported in patients with R/R diffuse large B-cell lymphoma, supporting the potential of odronextamab for management of indolent and aggressive B-NHL,” they added.

Source:

Kim TM, Taszner M, Novelli S, et al. Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma. Ann of Onc. Published online August 13, 2024. doi: 10.1016/j.annonc.2024.08.2239