嵌合抗原受体T细胞治疗消化道恶性肿瘤疗效及安全性的Meta分析

Meta-analysis of the efficacy of chimeric antigen receptor T cells therapy in the treatment of gastrointestinal malignant tumors

目的:系统评价嵌合抗原受体T细胞(CAR-T)治疗消化道恶性肿瘤的疾病控制率、严重不良反应发生率及预后情况。方法:计算机检索PubMed、Embase、The Cochrane Library、CNKI、Wan Fang和VIP数据库,搜集利用CAR-T治疗消化道恶性肿瘤的队列研究,检索时限从建库截至2020年03月01日。由2位评价者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用R软件和stata12.0软件进行单组率的Meta分析。结果:共纳入6项相关研究,共计55例患者。单组率Meta分析结果显示,CAR-T治疗消化道恶性肿瘤的疾病控制率为53%[95%CI(0.38,0.67)];亚组分析和Meta回归结果显示,转导方式(P=0.0148)和给药途径(P=0.0148)是影响疾病控制率的主要因素。严重不良反应发生率为57%[95%CI(0.23,0.85)]。Kaplan-Meier生存曲线显示患者6个月的无进展生存(progression-free survival,PFS)和总生存(overall survival,OS)率为26.1%和50.0%,1年的PFS和OS率为8.7%和16.7%;中位PFS为(4.0±0.16)个月;中位OS为(5.7±2.33)个月。结论:CAR-T治疗消化道恶性肿瘤具有较好的疗效,转导方式和给药途径是影响疾病控制率的主要因素。虽然CAR-T相关的严重不良反应发生率较高,但均能被积极控制且不会危及生命;CAR-T治疗能明显改善患者预后,更多的临床经验需要进一步研究和积累。

Objective:To evaluate the efficacy,incidence of severe adverse reactions and prognosis of chimeric antigen receptor T cells(CAR-T)in the treatment of digestive tract malignant tumors.Methods:PubMed,Embase,The Cochrane Library,CNKI,Wan Fang and VIP were searched to identify the cohort studies on CAR-T for gastrointestinal malignant tumors from the establishment of databases to March 01,2020.Two researchers independently screened the literature,extracted data,and evaluated the risk of bias in the included studies,using R software and stata12.0 software for single group rate Meta-analysis.Results:A total of 55 patients were included in 6 related studies.The results of Meta-analysis of single group rate showed that the disease control rate of CAR-T in the treatment of gastrointestinal malignant tumors was 53%[95%CI(0.38,0.67)].The results of subgroup analysis showed that transduction mode(P=0.0148)and administration method(P=0.0148)were the main factors affecting the disease control rate.The incidence of severe adverse reaction is 57%[95%CI(0.23,0.85)].The Kaplan-Meier survival curve shows that the progression-free survival and overall survival of 6 months were 26.1%and 50.0%,and the progression-free survival and overall survival of 1 year were 8.7%and 16.7%,respectively.The median PFS was(4.0±0.16)months,and the median OS was(5.7±2.33)months.Conclusion:CAR-T has a good effect for gastrointestinal malignant tumors,and the transduction mode and administration method are the main factors affecting the disease control rate.Although the incidence of CAR-T related severe adverse reaction is high,it can be actively controlled without life-threatening.CAR-T treatment can significantly improve the prognosis of patients,and we need to further study and accumulate more clinical experience.