双靶点嵌合抗原受体-T细胞治疗复发难治多发性骨髓瘤患者疗效和安全性的Meta分析  

Efficacy and Safety of Dual-targeted Chimeric Antigen Receptor-T Cell Therapy in Patients with Refractory-relapsed Multiple Myeloma:a Meta-analysis

作　　者：于海搏 张天宇 李新[1] 张佳佳[1] 申曼[1] 詹晓凯[1] 汤然 范斯斌 赵凤仪 黄仲夏[1] YU Haibo;ZHANG Tianyu;LI Xin;ZHANG Jiajia;SHEN Man;ZHAN Xiaokai;TANG Ran;FAN Sibin;ZHAO Fengyi;HUANG Zhongxia(Department of Hematology and Oncology,Beijing Chao-yang Hospital,Capital Medical University,Beijing 100020,China)

机构地区：[1]首都医科大学附属北京朝阳医院血液与肿瘤科,北京市100020

出　　处：《中国全科医学》2024年第8期985-994,共10页Chinese General Practice

基　　金：北京市科技计划项目(Z171100000417010);北京市石景山区卫生与健康委员会医学重点学科建设项目(石卫健医发〔2021〕2号)。

摘　　要：背景嵌合抗原受体(CAR)-T细胞免疫疗法已在多发性骨髓瘤(MM)中取得较好的疗效,最常见的靶点为B细胞成熟抗原(BCMA)。单靶点CAR-T细胞免疫疗法的缺点是会导致疾病抵抗和复发,可能与抗原逃逸有关。为此,改进开发了双靶点CAR-T细胞治疗复发难治多发性骨髓瘤(RRMM),此方面尚缺乏系统的临床分析。目的对RRMM患者应用双靶点CAR-T细胞免疫疗法治疗的有效性及安全性进行Meta分析。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网7个数据库中有关双靶点CAR-T细胞治疗RRMM的单组率研究,检索时限为建库至2023-02-06。由2名研究人员使用自制的数据表单来提取收集数据,并采用非随机对照试验方法学评价指标进行文献质量评价。采用R Studio软件进行数据分析。结果共纳入9篇文献,包括200例既往接受过多线治疗的RRMM患者。双靶点CAR-T细胞疗法根据不同靶点可分为4类:BCMA+CD19、BCMA+CD38,BCMA+跨膜剂与钙调节亲环素配体的相互作用者(TACI)、BCMA+人信号淋巴细胞激活分子家族成员7(CS1),其中BCMA+CD19靶点的研究较多。根据输注形式不同CAR-T细胞疗法可分为4类:双特异性CAR-T细胞、联合或序贯输注两种不同CAR-T细胞、双顺反子结构、共转导。Meta分析显示,双靶点CAR-T细胞治疗RRMM的总缓解率(ORR)为90.0%(95%CI=0.849~0.943),完全缓解率(CRR)为54.6%(95%CI=0.416~0.673),微小残留病(MRD)阴性率为75.6%(95%CI=0.489~0.952),髓外病变(EMD)总缓解率为55.1%(95%CI=0.234~0.851),最后一次随访时的复发率为29.7%(95%CI=0.141~0.454),最后一次随访时的生存率为75.6%(95%CI=0.554~0.915),3~4级细胞释放因子综合征(CRS)发生率为16.4%(95%CI=0.094~0.245),神经毒性(ICANS)发生率为4.0%(95%CI=0~0.120)。敏感性分析提示结果稳定。Egger's检验结果显示,ORR(P=0.03)及EMD总缓解率(P=0.02)提示存在一定的偏倚风险;CRR(P=Background Chimeric antigen receptor(CAR)-T cell immunotherapy has achieved good therapeutic effect in multiple myeloma(MM),and the most common target is B cell maturation antigen(BCMA).The disadvantage of single target CAR-T cell immunotherapy is that it can lead to disease resistance and recurrence,which may be related to antigen escape.Therefore,the dual-targeted CAR-T cell therapy for refractory-relapsed multiple myeloma(RRMM)has been improved and developed,but there is still a lack of systematic clinical analysis in this field.Objective A meta-analysis was conducted on the efficacy and safety of dual-targeted CAR-T cell therapy for RRMM patients.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,and VIP were searched for single-group rate studies on dual-targeted CAR-T cell therapy in patients with RRMM from inception to 2023-02-06.The data were extracted for collection by 2 investigators using a self-designed form and the quality of literature was evaluated using the methodological index for non-randomized studies(MINORS).The data analysis was conducted using RStudio software.Results A total of 9 clinical studies,involving 200 RRMM patients who had previously received multi-line therapy were included in the study.Dual-targeted CAR-T cell therapy can be mainly divided into four categories based on different targets of BCMA/CD19,BCMA/CD38,BCMA/TACI,and BCMA/CS1,of which the BCMA+CD19 target is more studied.Dual-targeted CAR-T cell therapy also can be divided into four categories of bispecific categories,combined/sequential infusion of two different CAR-T cells,bicistronic or cotransduction according to the different forms of infusion.Meta-analysis showed that the overall response rate(ORR)of dual-targeted CAR-T cells for RRMM was 90.0%(95%CI=0.849-0.943),and the complete response rate(CRR)was 54.6%(95%CI=0.416-0.673),the negative rate of minimal residual disease(MRD)was 75.6%(95%CI=0.489-0.952),the ORR of extramedullary diseases(EMD)was 55.1%(95%CI=0.234-0.851),the recurrence rate at the

关 键 词：多发性骨髓瘤 复发难治多发性骨髓瘤 双靶点CAR-T细胞免疫疗法 META分析 

分 类 号：R733.3[医药卫生—肿瘤]