Comparative effectiveness of CAR-T and bispecific antibodies in relapsed/refractory large B-cell lymphoma: A network meta-analysis of phase III trials.

Abstract

7090 Background: Second-line and later-line cellular therapies and bispecific antibodies have transformed the management of relapsed/refractory large B-cell lymphoma (LBCL), yet comparative efficacy across platforms remains uncertain due to the absence of head-to-head trials. We conducted a network meta-analysis (NMA) to compare disease control and overall survival (OS) across contemporary randomized phase III studies, representing the first synthesis of contemporary CAR-T and bispecific antibody phase III data. Methods: A frequentist graph-theoretical NMA was performed using trial-level hazard ratios (HRs) extracted from five randomized phase III trials (ZUMA-7, TRANSFORM, BELINDA, STARGLO, SUNMO). Treatments included axicabtagene ciloleucel, lisocabtagene maraleucel, tisagenlecleucel, glofitamab-GemOx, mosunetuzumab-polatuzumab, and chemoimmunotherapy as the reference. Outcomes were disease control (EFS/PFS) and OS. Random-effects models were applied, and P-scores were used to rank treatment hierarchy. Results: Five trials encompassing approximately 2,000 patients were included. For disease control, lisocabtagene maraleucel (HR 0.35, 95% CI 0.23–0.53), axicabtagene ciloleucel (HR 0.40, 95% CI 0.31–0.51), glofitamab-GemOx (HR 0.40, 95% CI 0.28–0.57), and mosunetuzumab-polatuzumab (HR 0.41, 95% CI 0.29–0.58) each significantly improved outcomes, whereas tisagenlecleucel did not (HR 1.07, 95% CI 0.82–1.40). Ranking favored lisocabtagene maraleucel (P-score 0.82), followed by axicabtagene ciloleucel (0.67), glofitamab-GemOx (0.67), and mosunetuzumab-polatuzumab (0.64). For OS, lisocabtagene maraleucel (HR 0.59, 95% CI 0.40–0.87), glofitamab-GemOx (HR 0.62, 95% CI 0.43–0.89), and axicabtagene ciloleucel (HR 0.73, 95% CI 0.55–0.97) significantly improved survival, while mosunetuzumab-polatuzumab showed a non-significant favorable trend (HR 0.80, 95% CI 0.52–1.24). Tisagenlecleucel did not improve OS (HR 1.24, 95% CI 0.83–1.85). OS rankings again favored lisocabtagene maraleucel (P-score 0.84), followed by glofitamab-GemOx (0.80) and axicabtagene ciloleucel (0.61). Conclusions: Across randomized phase III evidence, lisocabtagene maraleucel demonstrated the highest probability of being the most effective therapy for both disease control and overall survival in relapsed/refractory LBCL, followed closely by glofitamab-GemOx and axicabtagene ciloleucel, while tisagenlecleucel consistently ranked lowest. Although limited by cross-trial heterogeneity inherent to indirect comparisons, these findings highlight meaningful differences across platforms and may inform treatment sequencing while prospective head-to-head studies mature.