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Review
. 2019 Jan 7;11(1):47.
doi: 10.3390/cancers11010047.

Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety-A Systematic Review with Meta-Analysis

Wen-Liang Yu  1   2 , Zi-Chun Hua  3   4   5
Affiliations
Review

Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety-A Systematic Review with Meta-Analysis

Wen-Liang Yu et al. Cancers (Basel). .

Abstract

Chimeric antigen receptors T cells (CAR T) had been used for treating various tumor patients in clinic, and owned an incredible efficacy in part of malignancies. However, CAR T therapy remains controversial due to doubts about its efficacy and safety in the clinical treatment of various malignancies. A total of 997 tumor patients from 52 studies were included in this review. Eligible studies were searched and reviewed from the databases of PubMed, Web of Science, Wanfang and Clinicaltrials.gov. Then meta-analysis and subgroup analysis were used to investigate the overall response rate (ORR), complete response rate (CRR), common side effect rate (CSER) and relapse rate (RR) of CAR T therapy for patients in clinical researches, respectively. The results further confirmed that CAR T therapy had a higher response rate for hematologic malignancies. More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies. Cell cultured without the addition of IL-2 and total administration less than 10⁸ cells were recommended. This study offers a reference for future research regarding the application in solid and hematologic malignancies, side effects and relapse, and even the production processes of CAR T cells.

Keywords: chimeric antigen receptor T cell; meta-analysis; meta-regression analysis; relapse; response; side effect; subgroup analysis.

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Conflict of interest statement

The authors declare no competing interests. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Research results and quality assessment: (a) Flow-diagram of the literature selection process; (b) Results of the methodologic assessment by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tools.
Figure 2
Figure 2
The forest plots of meta-analysis about ORR: (a) Forest plot for ORR and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for ORR and CI in different B-cell malignancies patients of each study and the overall.
Figure 2
Figure 2
The forest plots of meta-analysis about ORR: (a) Forest plot for ORR and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for ORR and CI in different B-cell malignancies patients of each study and the overall.
Figure 3
Figure 3
The forest plots of meta-analysis about CRR: (a) Forest plot for CRR and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for CRR and CI in different B-cell malignancies patients of each study and the overall.
Figure 3
Figure 3
The forest plots of meta-analysis about CRR: (a) Forest plot for CRR and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for CRR and CI in different B-cell malignancies patients of each study and the overall.
Figure 4
Figure 4
The forest plots of meta-analysis about CSER and RR: (a) Forest plot for CRS rate and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for NS rate and CI in hematologic malignancies patients of each study and the overall; (c) Forest plot for RR and CI in solid and hematologic malignancies patients of each study and the overall.
Figure 4
Figure 4
The forest plots of meta-analysis about CSER and RR: (a) Forest plot for CRS rate and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for NS rate and CI in hematologic malignancies patients of each study and the overall; (c) Forest plot for RR and CI in solid and hematologic malignancies patients of each study and the overall.
Figure 4
Figure 4
The forest plots of meta-analysis about CSER and RR: (a) Forest plot for CRS rate and CI in solid and hematologic malignancies patients of each study and the overall; (b) Forest plot for NS rate and CI in hematologic malignancies patients of each study and the overall; (c) Forest plot for RR and CI in solid and hematologic malignancies patients of each study and the overall.
Figure 5
Figure 5
The forest plots of meta-regression analysis: (a) Forest plot for ORR and CI of cell culture with IL-2 addition and cell culture without IL-2 addition of each study and the overall; (b) Forest plot for CRR and CI of the total administration dose more than 108 cells and less than 108 cells of each study and the overall.
Figure 5
Figure 5
The forest plots of meta-regression analysis: (a) Forest plot for ORR and CI of cell culture with IL-2 addition and cell culture without IL-2 addition of each study and the overall; (b) Forest plot for CRR and CI of the total administration dose more than 108 cells and less than 108 cells of each study and the overall.
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