Matching-Adjusted Indirect Comparisons (MAICs) of Odronextamab Versus Mosunetuzumab and Epcoritamab for the Treatment of Patients with Relapsed/Refractory Follicular Lymphoma (R/R FL) after Two or More Lines of Systemic Therapy
Authors: Jagadeesh Deepa , Novelli Silvana , Luminari Stefano , Taszner Michal , Merli Michele , Xu Yingzxin , Kamat Siddhesh , Mastikhina Liza , Ambati Srikanth , Chen Jenny , Chan Keith , Cope Shannon , Keeping Sam , Caisip Clyde , Mohamed Hesham , Chaudhry Aafia , Harnett James , Villasboas Bisneto Jose C. 
Published: December 2024

Introduction
In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort study, odronextamab monotherapy demonstrated encouraging clinical efficacy, generally manageable safety, and maintenance of patient-reported outcomes in R/R FL (Chong et al. AACR 2024; Tessoulin et al. ASH 2023). In the absence of head-to-head clinical trials comparing CD20×CD3 bispecific antibodies in R/R FL, two unanchored MAICs were conducted to evaluate the efficacy of odronextamab versus mosunetuzumab and epcoritamab in patients with R/R FL in the third-line or later (3L+) setting.
Methods
Patient-level data from the ELM-2 R/R FL cohort receiving odronextamab (N=128; data cutoff: October 2023) were compared with published data from similar cohorts in the GO29781 trial of mosunetuzumab (N=90; Budde et al. Lancet Oncol 2022) and EPCORE NHL-1 trial of epcoritamab (N=128; Linton et al. Lancet Haematol 2024). To adjust for baseline differences in the trial populations, a priori-identified prognostic variables (progression of disease within 2 years, primary refractory, refractory to last line of therapy [LOT], number of prior LOTs, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group performance status, Follicular Lymphoma International Prognostic Index, age at start of LOT, and Ann Arbor disease stage) were included in the base-case MAICs. Two additional variables (double refractory and prior autologous stem cell transplant), reported in ELM-2 and the comparator studies, were included in a sensitivity analysis. The MAICs reported here were focused on response outcomes as assessed by independent central review, which were reported across trials. Relative treatment effects before and after matching were presented as odds ratios (ORs), along with 95% confidence intervals (CIs).
Results
The effective sample size for odronextamab was 102.0 after matching with mosunetuzumab and 90.6 after matching with epcoritamab in the base-case MAICs. All key prognostic variables were balanced between ELM-2 and both comparator trials in each analysis. Before and after matching, odronextamab demonstrated comparable objective response rates (ORRs) and significantly higher complete response (CR) rates versus mosunetuzumab (before matching: ORR 80.5% vs 80.0%, OR 1.03 [95% CI 0.52-2.03], p=0.93; CR rate 73.4% vs 60.0%, OR 1.84 [95% CI 1.04-3.28], p=0.04; after matching: ORR 83.5% vs 80.0%, OR 1.27 [95% CI 0.61-2.65], p=0.53; CR rate 75.7% vs 60.0%, OR 2.08 [95% CI 1.12-3.86], p=0.02). Odronextamab demonstrated numerically higher CR rates versus epcoritamab before and after matching (before matching: CR rate 73.4% vs 62.5%, OR 1.66 [95% CI 0.98-2.82], p=0.06; after matching: CR rate 69.4% vs 62.5%, OR 1.36 [95% CI 0.77-2.41], p=0.29). The ORRs of odronextamab and epcoritamab were comparable before matching (ORR 80.5% vs 82.0%, OR 0.90 [95% CI 0.48-1.69], p=0.75) and after matching (ORR 78.1% vs 82.0%, OR 0.78 [95% CI 0.40-1.53], p=0.47). Consistent results were observed in the sensitivity analyses.
Conclusions
In the absence of head-to-head clinical trials comparing bispecific antibodies in the setting of 3L+ FL, MAICs demonstrate that odronextamab was associated with higher CR rates compared with mosunetuzumab and epcoritamab. Since achieving a CR in the R/R FL setting is an important treatment goal, our results highlight the potential of odronextamab as an effective treatment option in R/R FL.