Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma.

in Annals of oncology : official journal of the European Society for Medical Oncology by T M Kim, M Taszner, S Novelli, S-G Cho, J C Villasboas, M Merli, A J Ubieto, B Tessoulin, L M Poon, D Tucker, J Walewski, S Yi, Y Song, G Chong, E Bachy, S Guidez, A Alonso, D Jagadeesh, W Zhang, L Magnano, E Iskierka-Jażdżewska, M Tani, B Shen, A Uppala, M Zhu, S Shariff, J Brouwer-Visser, A Chaudhry, H Mohamed, S Ambati, S Luminari,

TLDR

  • Odronextamab is a new treatment option for patients with relapsed/refractory follicular lymphoma (FL) who have tried other treatments and failed. The study showed that odronextamab was effective in these patients, achieving an ORR of 80.0% and complete response rate of 73.4% at 20.1 months' efficacy follow-up. However, the study had limitations, such as a small sample size and short follow-up period. Future research should address these limitations to improve our understanding of odronextamab's effectiveness and safety.

Abstract

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. This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review. Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%). Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.

Overview

  • The study focuses on the efficacy and safety of odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory follicular lymphoma (FL) after ≥2 lines of systemic therapy. The methodology involves intravenous odronextamab in 21-day cycles with step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary objective is to evaluate the objective response rate (ORR) by independent central review. The study aims to answer the question of whether odronextamab is effective and safe in heavily pretreated R/R FL patients.

Comparative Analysis & Findings

  • The study compared odronextamab with previous treatments in patients with R/R FL. The results showed an ORR of 80.0% and complete response rate of 73.4% at 20.1 months' efficacy follow-up. The median duration of complete response was 25.1 months, and median progression-free survival was 20.7 months. The median overall survival was not reached. These findings suggest that odronextamab is effective in heavily pretreated R/R FL patients.

Implications and Future Directions

  • The study's findings highlight the potential of odronextamab as a new treatment option for R/R FL patients. However, the study has limitations, such as a small sample size and short follow-up period. Future research should address these limitations by increasing the sample size and extending the follow-up period. Additionally, further studies should evaluate odronextamab in combination with other therapies to improve its efficacy and safety.
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