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文章来源: http://www.ncbi.nlm.nih.gov/pubmed/26376680

Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis

ABSTRACT

Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed (p < 0.001, I2=88.3%).ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.

CD19嵌合抗原受体修饰T细胞对B细胞恶性肿瘤治疗的I期临床试验的有效性荟萃分析

摘要:

嵌合抗原受体（CAR）修饰的靶向CD19T细胞在B淋巴细胞恶性肿瘤例如慢性淋巴细胞白血病（CLL）、急性淋巴细胞白血病（ALL）和其他惰性淋巴瘤中展现了具有前景的治疗效果。然而，在不同的试验中，临床获益有很大的不同。这份荟萃分析调查了CD19 靶向的CAR-T细胞治疗B淋巴细胞恶性肿瘤1期临床试验的有效性（反应速度和存活时间），我们搜索了从1991年到2014年PubMed和Web of Science上出版的文章。使用随机效应模型计算汇总总有效率。通过小组分析和荟萃回归分析差异性。四十个临床试验，共计119名试验者，12个临床试验中有62名患者有资格进行无进展生存分析。整体CD19细胞的有效应为73%(95%的可信区间[CI]：46-94%)。评估的有效性被观察到具有明显的差异性（P＜0.001，I2 = 88.3%）。 ALL病人的有效性（(93%, 95% CI: 65-100%)）比CLL (62%, 95% CI: 27-93%)和淋巴患者(36%, 95% CI: 1-83%)更高。荟萃回顾分析表明淋巴细胞缺失和没有IL-2处理的T细胞是两个关键因素，治疗会有较好的临床效应。淋巴细胞缺失和高数量的CAR-T细胞输注会有一个更好的预后。总之，这一荟萃分析显示CD19 CAR-T细胞为基础的免疫治疗B淋巴细胞恶性肿瘤有较高的临床有效性。淋巴细胞缺失和增加注入CD19-CAR T细胞数量与疗效呈正相关，相反，不推荐使用IL-2处理T细胞。