CD19嵌合抗原受体T细胞治疗B细胞血液系统恶性肿瘤临床反应单组率的Meta分析

Clinical response rate of CD19 chimeric antigen receptor modified-T cells in the treatment of B cell hematological malignancies: a single rate meta-analysis

目的系统评价CD19嵌合抗原受体T细胞(CD19CART)治疗B细胞血液系统恶性肿瘤临床反应率。方法计算机检索Pub Med、EMbase、CNKI、Wan Fang Data和VIP数据库,搜集CD19CART治疗B细胞血液系统恶性肿瘤的队列研究,检索时限从2000年至2016年。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SPSS 16.0软件进行单个率的Meta分析。结果共纳入13个前瞻性队列研究。单组率的Meta分析结果显示,CD19CART治疗B细胞血液系统恶性肿瘤总体反应率为68%[95%CI(0.51,0.82)]。Kaplan-Meier评估CD19CART治疗后的6个月和1年的无进展生存率(PFS)分别为46%[95%CI(0.35,0.56)]和24%[95%CI(0.16,0.34)],中位持续时间为180天[95%CI(138,222)]。COX回归模型显示淋巴细胞清除术是影响PFS的唯一因素。结论 CD19CART治疗B细胞血液系统恶性肿瘤具有较好的临床反应率。淋巴细胞清除术是唯一对患者的反应率和PFS有重要影响的因素。受纳入研究数量和质量的限制,上述结论尚待开展更多高质量研究予以验证。

ObjectivesTo systematically review the clinical response rate of CD19 chimeric antigen receptor modified-T cells （CD19CART） in the treatment of B cell hematological malignancies.MethodsPubMed, EMbase, CNKI, WanFang Data and VIP databases were searched to collect cohort studies about CD19CART in the treatment of B cell hematological malignancies from 2000 to 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, a single rate meta-analysis was performed by R software and SPSS 16.0 software.ResultsA total of 13 prospective cohort studies were included. The results of single group rate meta-analysis showed that the overall pooled response rate of CD19 CART was 68% （95%CI 0.51 to 0.82）. The 6 months and 1-year PFS after CD19 CART infused by Kaplan-Meier were 46% （95%CI 0.35 to 0.56） and 24% （95%CI 0.16 to 0.34）, respectively. The median duration was 180 days （95%CI 138 to 222）. The COX regression model showed lymphodepletion to be the only influence factor of PFS.ConclusionsCD19 CART has a good clinical response rate in the treatment of B cell hematological malignancies. Lymphodepletion is the only important impact on the response rate and PFS. Due to limited quality and quantity of included studies, more high quality studies are required to verify the above conclusions.