Outcomes of odronextamab in non-Hodgkin lymphoma: A systematic review and meta-analysis.

Abstract

e19006 Background: Emerging therapeutic strategies for Non-Hodgkin Lymphoma (NHL) include bispecific antibodies like odronextamab, a CD20×CD3 agent that directs T cells to destroy malignant B cells. This meta-analysis reviews the outcomes of odronextamab in the NHL. Methods: A systematic search was conducted on PubMed, Medline, and Embase following PRISMA guidelines and four studies reporting outcomes of Odronextamab in NHL were included after screening of 103 studies. Inter-study variance was assessed using the Der Simonian-Laird Estimator, and pooled analysis was conducted with 95% confidence intervals using the ‘meta’ package in R (version 4.16-2). Results: A total of 386 patients from 4 studies (2022-2024) were included for analysis. The median age was 61.5 (22-84) years and majority were male (62%, n=176). Studies included three clinical trials (phase 1, 2, and 3) and one retrospective analysis. NHL included Follicular lymphoma which was the most common type of NHL (73%, n=281) followed by Diffuse Large B cell lymphoma (DLBCL) (22%, n=85). 85% (n=232/273) had Ann Arbor stage III-IV and 59% (n=143/241) had FLIPI score 3-5. ECOG performance status was 0 (45%, n=123/273) and ≥1 (55%, n=150). 97% (n=373) received ≥2 prior lines of therapy. The pooled rates of overall response (OR), complete response (CR), and partial response (PR) were 62.7% (95% CI 0.58-0.68, I 2 =92%, p<0.01, n=378), 48.4% (95% CI 0.43-0.54, I 2 =95%, p<0.01, n=378), and 11.1% (95% CI 0.08-0.15, I 2 =70%, p=0.02, n=378), respectively. Median duration of CR was 11.8 (2.2-31.1) months. The pooled rates of stable disease (SD) and progressive disease (PD) were 22.7% (95% CI 0.18-0.28, I 2 =0%, p=0.99, n=273) and 34.5% (95% CI 0.29-0.40, I 2 =90%, p<0.01, n=273), respectively. The pooled progression free survival (PFS) at 6, 12, 18, and 24-months was 68.8% (95% CI 0.63-0.75, I 2 =91%, p<0.01, n=250), 58.5% (95% CI 0.52-0.65, I 2 =82%, p=0.02, n=250), 49.2% (95% CI 0.43-0.55, I 2 =84%, p=0.01, n=250), and 43.6% (95% CI 0.38-0.50, I 2 =0%, p=0.42, n=250), respectively. Median duration of response was 23 (1.6-NE) months. The pooled rates of discontinuation and mortality were 63.8% (95% CI 0.58-0.69, I 2 =95%, p<0.01, n=286) and 12% (95% CI 0.08-0.16, I 2 =0%, p=0.37, n=273), respectively. The pooled rate of treatment emergent adverse events (TEAEs) was 79.9% (95% CI 0.75-0.85, I 2 =96%, p<0.01, n=286) and cytokine release syndrome (41%, n=117/286), neutropenia (23%, n=66), and pyrexia (17%, n=42) were the most common TEAEs. At 6, 12, and 24 months, Kim et al. reported overall survival (OS) of 89.8%, 86%, and 70.3%. Conclusions: This meta-analysis shows the good efficacy of odronextamab in the NHL with a modest safety profile. However, the meta-analysis is limited by a small sample size, necessitating the need for large randomized controlled trials in the future.