ABCL-411 Matching-Adjusted Indirect Comparison of Axicabtagene Ciloleucel Vs Odronextamab for the Treatment of Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) after 2 Prior Lines of Systemic Treatment

Context/Objective R/R disease is common in LBCL, and treatment options continue evolving. We estimated the comparative efficacy and safety of axicabtagene ciloleucel (axi-cel; autologous anti-CD19 CAR T-cell therapy) to odronextamab (anti-CD3×CD20 bispecific antibody) for treatment of patients with R/R LBCL and ≥2 prior lines of systemic therapy. Design/Setting/Patients Our matching-adjusted indirect comparisons (MAICs) used individual patient data (IPD) from the ZUMA-1 trial for axi-cel (cohorts 1&2; n=101) and aggregate-level data, with reconstructed pseudo-IPD for time-to-event outcomes, from the ELM-2 odronextamab trial (n=127). The MAICs adjusted for between-trial imbalances in prespecified, clinically relevant variables (International Prognostic Index score 3+, ECOG 0, disease stage III-IV, refractory last therapy, 3+ prior therapies, primary refractory, LBCL subtypes, prior autologous stem cell transplantation) by weighting ZUMA-1 patients’ data to align with the ELM-2 population. Time-to-event outcomes (OS and PFS) were analyzed using weighted Cox regression and restricted mean survival times (RMST), and dichotomous outcomes (overall response rate [ORR], complete response rate [CRR], adverse events) using weighted logistic regression. Neurotoxicity was not reported for ELM-2 and therefore not analyzed in this study. Sensitivity analyses added ZUMA-1 cohorts 4&6 and varied matching variables. Results For OS, the population-adjusted hazard ratio (HR) of 0.52 (95% CI, 0.34-0.80) and the 36-month RMST mean difference of 7.53 months (95% CI, 2.20-12.86), favored axi-cel over odronextamab. Axi-cel also demonstrated superior PFS (HR, 0.51; 95% CI, 0.33-0.79), ORR (odds ratio [OR], 2.72; 95% CI, 1.00-7.39), and CRR (OR, 2.34; 95% CI, 1.05-5.26) relative to odronextamab. Axi-cel versus odronextamab had higher odds of grade 3+ cytokine release syndrome (OR, 4.21; 95% CI, 1.23-14.45), which reduced to 3.26 (95% CI, 0.97-10.99) when including evidence with updated safety protocols (ZUMA-1 cohorts 4&6). The treatments showed no significant differences for thrombocytopenia and neutropenia; risk of grade 5 adverse events was lower for axi-cel versus odronextamab (OR, 0.16; 95% CI, 0.05-0.45). Conclusions MAIC results suggest that one-time axi-cel treatment is associated with superior efficacy, including OS and PFS, relative to odronextamab, which is used in a treat-to-progression fashion. Although odronextamab patients appear to be at lower risk of grade 3+ CRS, these differences may be reduced using current safety protocols.