关键词: 多发性骨髓瘤, 嵌合抗原受体T淋巴细胞, 总反应率, 不良事件, 细胞因子释放综合征, Meta分析, 系统评价

Abstract: Background　Multiple myeloma（MM）is a malignant plasma cell neoplasm，which is refractory，and prone to relapse.Moreover，there is no cure for it.Chimeric antigen receptor T-cell（CAR-T）is an innovative immunotherapy with great potentials in the treatment of MM，but its efficacy and safety are not well evaluated currently.Objective　To evaluate the efficacy and safety of CAR-T in the treatment of MM systematically，providing evidence-based medical basis for safe and efficient application of the therapy.Methods　Databases of PubMed，EMBase，and the Cochrane Library were systematically searched for published clinical trials articles in English about CAR-T for MM from inception to November 2019.The overall response rate，incidence of severe adverse events（≥ grade 3）and incidence of cytokine release syndrome were used as major therapeutic outcome indicators.R software was used to perform a Meta-analysis of major therapeutic outcomes of patients with CAR-T.Meta-regression analysis was conducted to further analyze major therapeutic outcomes in patients with CAR-T according to pretreatment regimen，costimulatory molecule and the antigen epitope type of CAR-T.Results　A total of 8 articles were included，including 191 patients.Meta-analysis showed that the overall response rate of CAR-T treatment of MM was 0.88 〔95% CI（0.83，0.93）〕，the incidence of serious adverse events was 0.90 〔95%CI（0.83，0.98）〕，and the incidence of cytokine release syndrome was 0.92〔95%CI（0.85，1.00）〕.Further Meta regression analysis suggested：（1）The incidence of severe adverse reactions and cytokine release syndrome differed significantly by pretreatment regimen（P=0.013，P<0.001）.To be specific，Flu+Cy ，Cy pretreatment and no pretreatment subgroup had higher incidence of severe adverse reactions HDM+ASCT pretreatment subgroups（P<0.05）.（2）Costimulatory molecule 4-1BB subgroup had higher overall response rate but lower incidence of severe adverse reactions than costimulatory molecule CD28 subgroup（P<0.05）.（3）The overall response rate，and incidence of severe adverse reactions and cytokine release syndrome in MM patients with different antigen epitope types were statistically significant（P=0.004，0.049，0.023）.BCMA subgroup had lower overall response rate than LCAR-B38M and BCMA +CD19 subgroups（P<0.05），and had higher incidence of severe adverse reactions and cytokine release syndrome than CD19 subgroups（P<0.05）.The incidence of severe adverse reactions and cytokine release syndrome in BCMA+CD19 subgroup was higher than that of CD19 subgroup（P<0.05）.Conclusion　CAR-T may have a good effect on MM，although there are certain controllable safety risks.The pretreatment regimen，costimulatory molecule，and CAR-T antigen type may be factors associated with its efficacy and safety.Due to small sample size and different qualities of the included studies，the above conclusions need to be further verified by large-sample，high-quality randomized controlled clinical trials.

Key words: Multiple myeloma, Chimeric antigen receptor T cell, Overall response rate, Adverse events, Cytokine release syndrome, Meta-analysis, System evaluation