CD19靶向的嵌合抗原受体(CAR)T细胞是用于管理B细胞恶性肿瘤的最显著的细胞疗法之一。然而,长期无病生存仍然是一个需要克服的挑战.这里,我们评估了不同铰链的影响,跨膜(TM),和共刺激CAR结构域,以及制造条件,蜂窝产品类型,剂量,病人的年龄,和肿瘤类型对用CD19CART细胞治疗的B细胞癌患者临床结局的影响。主要结果定义为最佳完全缓解(BCR),次要结局是最佳客观缓解(BOR)和12个月总生存期(OS).考虑的协变量是铰链的类型,TM,和CAR中的共刺激结构域,CAR-T细胞制造条件,用CAR转导的细胞群,CART细胞输注的数量,注射的CART细胞量/Kg,CD19汽车类型(名称),肿瘤类型,和年龄。56项研究(3493例)纳入系统评价,46项(3421例)纳入荟萃分析。整体BCR率为56%,60%OS和75%BOR。年轻患者的BCR患病率明显较高,而OS无差异。汽车铰链中CD28的存在,TM,和共刺激结构域改善了所有评估结果.从1到490万细胞/kg的剂量导致更好的临床结果。我们的数据还表明,无论患者是否有很高的客观反应,他们可能从CD19CART治疗中获益.这种荟萃分析是一种关键的假设生成工具,缺乏随机临床试验和大型观察性研究的CD19CART细胞文献中的捕获效应。
CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient\'s age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic
review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR\'s hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.