Real-World Comparison of Axicabtagene Ciloleucel and Lisocabtagene Maraleucel in Relapsed/Refractory Large B-Cell Lymphoma: A Target Trial Emulation.

BACKGROUND: Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) are approved chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory large B-cell lymphoma (r/r LBCL). However, no head-to-head randomized trials have directly compared their effectiveness and safety. OBJECTIVES: To compare the real-world effectiveness and safety of axi-cel and liso-cel in adults with r/r LBCL using a target trial emulation. METHODS: Using a target trial emulation framework, we conducted a retrospective study of data from the TriNetX US Collaborative Network to compare axi-cel and liso-cel in adults with r/r LBCL. Time zero was defined as the date of CAR T-cell infusion, and patients were followed until the occurrence of an outcome, last encounter, or administrative censoring. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Primary outcomes were overall survival (OS) and event-free survival (EFS). Safety outcomes included the cumulative incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) at 30, 60, and 90 days. RESULTS: Among 1,070 patients (709 axi-cel; 361 liso-cel), baseline characteristics were well balanced after IPTW. Median weighted OS was not reached for axi-cel and was 41.4 months for liso-cel (weighted hazard ratio [HR], 1.20; 95% CI, 0.87-1.66). Median weighted EFS was not reached for axi-cel and was 31.2 months for liso-cel (weighted HR, 1.22; 95% CI, 0.89-1.67). Secondary time-varying analyses suggested differences in mortality hazards during longer follow-up, with a higher relative hazard of death for liso-cel at 24 months (weighted HR: 1.76; 95% CI, 1.01-3.06). Liso-cel was associated with lower risks of CRS and ICANS across all time points (CRS at 30 days: weighted RR, 0.68; 95% CI, 0.56-0.83). Severe CRS was rare and similar across groups, whereas severe ICANS was more frequent with axi-cel (10.9% vs 5.8%). CONCLUSIONS: Primary IPTW analyses showed no significant difference in OS and EFS between axi-cel and liso-cel. Secondary time-varying analyses suggested differences in OS hazards during longer follow-up, favoring axi-cel. Liso-cel demonstrated a more favorable safety profile, with lower risk of CRS and ICANS compared with axi-cel. These findings should be interpreted cautiously given differential follow-up between treatment groups and the potential for residual confounding.