Comparative efficacy and safety of CD19 chimeric antigen receptor T-cell therapy versus CD3/CD20 bispecific antibodies in relapsed/refractory mantle cell lymphoma: a meta-analysis of clinical trials and real-world studies

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies and CD3/CD20-directed bispecific antibodies (BsAbs) showed high efficacy in relapsed/refractory mantle cell lymphoma, though comparative data are limited. We performed a meta-analysis of clinical trials and real-world evidence (RWE) studies, including 12 studies with 1392 patients: 4 CAR-T trials, 6 brexucabtagene autoleucel (brexu-cel) RWE studies, and 2 BsAb trials. Efficacy outcomes were similar, with overall response rates of 91%, 90%, 83%, and 86% ( P = 0.312) and complete response rates of 69%, 77%, 72%, and 78% ( P = 0.277) for brexu-cel trials, brexu-cel RWE studies, lisocabtagene maraleucel (liso-cel) trial, and BsAb trials, respectively. Progression-free survival rates at 12 months were 67.8% (95% CI 50.8–81.1), 57.3% (95% CI 50.1–64.3), 52.8% (95% CI 41.4–64.0), and 65.3% (95% CI 45.9–80.7), respectively ( P = 0.430), and overall survival rates at 12 months were 83.9% (95% CI 65.2–93.5), 75.2% (95% CI 71.8–78.4), 61.8% (95% CI 50.8–71.7), and 77.6% (95% CI 67.3–85.4), respectively, modestly lower with liso-cel than brexu-cel and BsAbs ( P = 0.037). Brexu-cel had similar cytokine release syndrome rates in trials versus RWE studies (all-grade 93% vs 89%; grade ≥3: 8% vs 11%), higher than in liso-cel (61%; 1%) and BsAb trials (57%; 4%) ( P < 0.001 for all-grade and P = 0.002 for grade ≥3). Immune effector cell-associated neurotoxicity syndrome rates were also similar in brexu-cel trials versus RWE studies (all-grade 71% vs 60%; grade ≥3: 29% vs 24%), higher than in liso-cel (31%; 9%) and BsAb trials (7%; 0%) ( P < 0.001 for both all-grade and grade ≥3). Overall, CAR-T and BsAbs demonstrated broadly comparable efficacy, with BsAbs and liso-cel demonstrating lower toxicity than brexu-cel.