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抗BCMA嵌合抗原受体T细胞治疗复发/难治性多发性骨髓瘤的有效性和安全性:前瞻性临床试验的综合综述与荟萃分析

Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.

作者信息

Hu Dingyuan, Chen Liming, Yan Diqin, Dong Wenliang, Chen Min, Niu Suping, Wang Simin, Zhang Jiaojiao, Nie Xiaoyan, Fang Yi

机构信息

Clinical Trial Institution, Peking University People's Hospital, Beijing, China.

Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.

出版信息

Front Pharmacol. 2023 Jun 20;14:1149138. doi: 10.3389/fphar.2023.1149138. eCollection 2023.

Abstract

Chimeric antigen receptor T cells treatment targeting B cell maturation antigen (BCMA) is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) and has demonstrated outstanding outcomes in clinical studies. The aim of this comprehensive review and meta-analysis was to summarize the effectiveness and safety of anti-BCMA CAR-T treatment for patients with relapsed/refractory multiple myeloma (RRMM). Our research identifies variables influencing outcome measures to provide additional evidence for CAR-T product updates, clinical trial design, and clinical treatment guidance. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard was followed for conducting this comprehensive review and meta-analysis, which was submitted to PROSPERO (CRD42023390037). From the inception of the study until 10 September 2022, PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and WanFang databases were searched for eligible studies. Stata software (version 16.0) was used to assess effectiveness and safety outcomes. Out of 875 papers, we found 21 relevant trials with 761 patients diagnosed as RRMM and were given anti-BCMA CAR-T treatment. The overall response rate (ORR) for the entire sample was 87% (95% CI: 80-93%) complete response rate (CRR) was 44% (95% CI: 34-54%). The minimal residual disease (MRD) negativity rate within responders was 78% (95% CI: 65-89%). The combined incidence of cytokine release syndrome was 82% (95% CI: 72-91%) and neurotoxicity was 10% (95% CI: 5%-17%). The median progression-free survival (PFS) was 8.77 months (95% CI: 7.48-10.06), the median overall survival (OS) was 18.87 months (95% CI: 17.20-20.54) and the median duration of response (DOR) was 10.32 months (95% CI: 9.34-11.31). According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety. Subgroup analysis confirmed the anticipated inter-study heterogeneity and pinpointed potential factors contributing to safety and efficacy, which may help with the development of CAR-T cell studies and lead to optimized BCMA CAR-T-cell products. Clinicaltrials.gov, PROSPERO, CRD42023390037.

摘要

靶向B细胞成熟抗原(BCMA)的嵌合抗原受体T细胞疗法是复发/难治性多发性骨髓瘤(RRMM)的一种新兴治疗选择,并且在临床研究中已显示出出色的疗效。本综述和荟萃分析的目的是总结抗BCMA嵌合抗原受体T细胞(CAR-T)疗法治疗复发/难治性多发性骨髓瘤(RRMM)患者的有效性和安全性。我们的研究确定了影响疗效指标的变量,为CAR-T产品更新、临床试验设计和临床治疗指导提供更多证据。本综述和荟萃分析遵循系统评价和荟萃分析的首选报告项目(PRISMA)标准,并已提交至国际前瞻性系统评价注册库(PROSPERO,注册号:CRD42023390037)。从研究开始至2022年9月10日,检索了PubMed、科学网、EMBASE、考克兰图书馆、中国知网和万方数据库,以查找符合条件的研究。使用Stata软件(版本16.0)评估有效性和安全性结果。在875篇论文中,我们找到了21项相关试验,共有761例被诊断为RRMM的患者接受了抗BCMA CAR-T治疗。整个样本的总缓解率(ORR)为87%(95%置信区间:80%-93%),完全缓解率(CRR)为44%(95%置信区间:34%-54%)。缓解者中的微小残留病(MRD)阴性率为78%(95%置信区间:65%-89%)。细胞因子释放综合征的合并发生率为82%(95%置信区间:72%-91%),神经毒性为10%(95%置信区间:5%-17%)。无进展生存期(PFS)的中位数为8.77个月(95%置信区间:7.48-10.06),总生存期(OS)的中位数为18.87个月(95%置信区间:17.20-20.54),缓解持续时间(DOR)的中位数为10.32个月(95%置信区间:9.34-11.31)。根据这项荟萃分析,接受抗BCMA CAR-T治疗的RRMM患者已显示出有效性和安全性。亚组分析证实了预期的研究间异质性,并确定了影响安全性和疗效的潜在因素,这可能有助于CAR-T细胞研究的开展,并带来优化的BCMA CAR-T细胞产品。Clinicaltrials.gov,PROSPERO,CRD42023390037

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e931/10318167/618eac113105/fphar-14-1149138-g001.jpg

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