CD19靶向CAR-T治疗复发/难治性弥漫大B细胞淋巴瘤疗效和安全性的Meta分析

Efficacy and safety of CD19-targeted CAR-T therapy for relapsed/refractory diffuse large B-cell lymphoma:a meta-analysis

目的探讨CD19靶向嵌合抗原受体T细胞(CAR-T)治疗复发/难治性弥漫大B细胞淋巴瘤(R/R DLBCL)的疗效及其不良反应,为更加合理、高效地应用CAR-T提供循证依据。方法检索PubMed、Embase、Cochrane、ClinicalTrials.gov、中国知网、万方数据库、维普网并筛选从建库至2022年4月公开发表的CD19靶向CAR-T治疗R/R DLBCL的文献。以客观缓解率(ORR)、完全缓解率(CRR)和不良反应发生率作为结局指标,根据CAR-T细胞共刺激因子及研究类型的不同进行亚组分析,采用R 4.1.2软件进行Meta分析、敏感性分析和发表偏倚分析。结果共筛选出11篇文献,共计1466名患者。CD19靶向CAR-T细胞治疗R/R DLBCL的ORR为72.1%(95%CI:62.3%~81.9%),CRR为50.8%(95%CI:41.1%~60.5%),细胞因子释放综合征(CRS)发生率为77.5%(95%CI:65.6%~89.4%),神经毒性发生率为41.4%(95%CI:26.8%~56.1%)。亚组分析结果显示:共刺激因子CD28亚组患者的ORR、CRR、CRS发生率及神经毒性发生率均高于4-1BB亚组,观察性试验亚组患者的ORR、CRR、CRS发生率及神经毒性发生率均高于干预性试验亚组。结论CD19靶向CAR-T治疗R/R DLBCL具有较高的ORR、CRR,同时也具有较高的不良反应发生率。共刺激因子CD28亚组患者与4-1BB亚组相比,有更高的ORR、CRR、CRS发生率和神经毒性发生率。

OBJECTIVE To investigate the efficacy and adverse reaction of CD19-targeted chimeric antigen receptor T cells(CAR-T)in the treatment of relapsed/refractory diffuse large B-cell lymphoma(R/R DLBCL),so as to provide an evidence-based basis for more reasonable and efficient application of CAR-T.METHODS Retrieved from PubMed,Embase,Cochrane,ClinicalTrials.gov,CNKI,Wanfang,VIP database,the literature about CD19 targeted CAR-T in the treatment of R/R DLBCL that were published from the inception to April 2022 were screened.Taking objective remission rate(ORR),complete remission rate(CRR)and incidence of adverse reactions as outcome indicators,subgroup analysis was performed according to the costimulatory factor of CAR-T and the different types of research.R 4.1.2 software was used for meta-analysis,sensitivity analysis and publication bias analysis.RESULTS A total of 11 pieces of literature were screened,involving 1466 patients.The ORR of CD-19 targeted CAR-T cells in the treatment of R/R DLBCL was 72.1%(95%CI:62.3%-81.9%),the CRR was 50.8%(95%CI:41.1%-60.5%),the incidence of cytokine release syndrome(CRS)was 77.5%(95%CI:65.6%-89.4%),the incidence of neurotoxicity was 41.4%(95%CI:26.8%-56.1%).Results of subgroup analysis showed that the incidence of ORR,CRR,CRS and neurotoxicity in costimulatory factor CD28 subgroup were higher than those in 4-1BB subgroup.The incidence of ORR,CRR,CRS and neurotoxicity in the observational experimental subgroup were higher than those in the intervention experimental subgroup.CONCLUSIONS CD19 targeted CAR-T has high ORR and CRR for R/R DLBCL,as well as higher incidence of adverse reactions.Co-stimulatory factor CD28 has higher ORR,CRR,CRS incidence and neurotoxicity incidence than 4-1BB.