Techaapornkun Pisanupong, Rojpalakorn Waranyoo, Mejun Nuthchaya, Khaniya Asmita, Thammahong Arsa, Thu May Soe, Hirankarn Nattiya, Pitakkitnukun Palada
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Medical Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Ann Hematol. 2025 Sep 9. doi: 10.1007/s00277-025-06524-6.
Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis. We systematically searched PubMed, Embase, and the Cochrane Library up to October 2, 2024, for studies evaluating BCMA-directed CAR-T or BiTEs therapies in R/R MM. Twenty-six studies comprising 2,246 patients were included. A random-effects meta-analysis and meta-regression were performed to assess pooled efficacy and safety outcomes and examine the impact of CAR-T constructs and patient-level characteristics. CAR-T therapies showed a higher overall response rate (ORR) of 84% and CR/stringent CR (CR/sCR) of 55%, compared to 65% and 41%, respectively, for BiTEs. Dual-targeted CAR-T therapies (e.g., anti-BCMA + anti-CD38/CD19) had the highest efficacy (ORR 92%). CAR-T was associated with more hematologic toxicity and cytokine release syndrome, while BiTEs had fewer severe events but higher infection rates. Meta-regression confirmed CAR-T significantly outperformed BiTEs. Unlike previous analyses, this study integrates interventional and real-world data, evaluates dual-target CAR-Ts, and offers detailed product- and subgroup-level comparisons. BCMA-targeted CAR-T therapies yield deeper responses but greater toxicity. BiTEs offer safer, though less potent, alternatives, supporting more personalized decisions in BCMA-directed immunotherapy for MM.
尽管治疗取得了进展，但多发性骨髓瘤（MM）仍然无法治愈，尤其是在复发/难治性（R/R）病例中。B细胞成熟抗原（BCMA）是新型免疫疗法的关键靶点，包括嵌合抗原受体T细胞（CAR-T）疗法和双特异性T细胞衔接器（BiTE），它们在疗效、毒性和可及性方面存在差异。通过系统评价和荟萃分析比较BCMA导向的CAR-T疗法和BiTE在R/R MM中的疗效和安全性。我们系统检索了截至2024年10月2日的PubMed、Embase和Cochrane图书馆，以查找评估BCMA导向的CAR-T或BiTE疗法在R/R MM中的研究。纳入了26项研究，共2246例患者。进行随机效应荟萃分析和荟萃回归，以评估汇总的疗效和安全性结果，并检查CAR-T构建体和患者水平特征的影响。与BiTE分别为65%和41%相比，CAR-T疗法显示出更高的总缓解率（ORR），为84%，完全缓解/严格完全缓解（CR/sCR）为55%。双靶点CAR-T疗法（如抗BCMA + 抗CD38/CD19）疗效最高（ORR 92%）。CAR-T与更多的血液学毒性和细胞因子释放综合征相关，而BiTE严重事件较少，但感染率较高。荟萃回归证实CAR-T明显优于BiTE。与以往分析不同，本研究整合了干预性和真实世界数据，评估了双靶点CAR-T，并提供了详细的产品和亚组水平比较。以BCMA为靶点的CAR-T疗法产生更深的缓解，但毒性更大。BiTE提供了更安全但效力较低的替代方案，支持在MM的BCMA导向免疫治疗中做出更个性化的决策。
