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Meta-Analysis
. 2015 Oct 20;6(32):33961-71.
doi: 10.18632/oncotarget.5582.

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

Tengfei Zhang  1   2 , Ling Cao  1   3 , Jing Xie  4 , Ni Shi  5 , Zhen Zhang  1   3 , Zhenzhen Luo  1   3 , Dongli Yue  1   3 , Zimeng Zhang  6 , Liping Wang  3 , Weidong Han  7 , Zhongwei Xu  8 , Hu Chen  9 , Yi Zhang  1   3   10   11
Affiliations
Meta-Analysis

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

Tengfei Zhang et al. Oncotarget. .

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.

Keywords: B cell malignancies; CD19; chimeric antigen receptor; efficiency; meta analysis.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. Flow diagram of study selection process
Figure 2
Figure 2. Forest plot for response rates and confidence intervals in each study and the overall
Figure 3
Figure 3. Forest plot for response rates and confidence internals in ALL, CLL and lymphoma patients
Figure 4
Figure 4. Forest plot for response rates and confidence internals in patients received IL-2 administrated T cells and patients received no IL-2 administrated T cells
Figure 5
Figure 5. Forest plot for response rates and confidence internals in patients received lymphodepletion and patients without lymphodepletion
Figure 6
Figure 6. Progression-free survival (PFS) curves
A. the PFS for total 62 patients; B. patients benefited from lymphodepletion; C. patients benefited from more than 108 infused total CAR T cells.
See this image and copyright information in PMC

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