CD19嵌合抗原受體修飾T細胞對B細胞惡性*的I期臨床試驗的有效性薈萃分析
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-*) 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嵌合抗原受體修飾T細胞對B細胞惡性*的I期臨床試驗的有效性薈萃分析
摘要:
嵌合抗原受體（CAR）修飾的靶向CD19T細胞在B淋巴細胞惡性腫瘤例如慢性淋巴細胞白血病（CLL）、急性淋巴細胞白血病（ALL）和其他惰性淋巴瘤中展現了具有前景的治療效果。然而，在不同的試驗中，臨床獲益有很大的不同。這份薈萃分析調查了CD19 靶向的CAR-T細胞治療B淋巴細胞惡性腫瘤1期臨床試驗的有效性（反應速度和存活時間），我們搜索了從1991年到2014年PubMed和Web of Science上出版的文章。使用隨機效應模型計算匯總總有效率。通過小組分析和薈萃回歸分析差異性。四十個臨床試驗，共計119名試驗者，12個臨床試驗中有62名患者有資格進行無進展生存分析。整體CD19細胞的有效應為73%(95%的可信區間[CI]：46-94%)。評估的有效性被觀察到具有明顯的差異性（P＜0.001，I2 = 88.3%）。 ALL病人的有效性（(93%, 95% CI: 65-*)）比CLL (62%, 95% CI: 27-93%)和淋巴患者(36%, 95% CI: 1-83%)更高。薈萃回顧分析表明淋巴細胞缺失和沒有IL-2處理的T細胞是兩個關鍵因素，治療會有較好的臨床效應。淋巴細胞缺失和高數量的CAR-T細胞輸注會有一個更好的預后。總之，這一薈萃分析顯示CD19 CAR-T細胞為基礎的*B淋巴細胞惡性腫瘤有較高的臨床有效性。淋巴細胞缺失和增加注入CD19-CAR T細胞數量與療效呈正相關，相反，不*使用IL-2處理T細胞。
