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

作者信息

Zhang Tengfei, Cao Ling, Xie Jing, Shi Ni, Zhang Zhen, Luo Zhenzhen, Yue Dongli, Zhang Zimeng, Wang Liping, Han Weidong, Xu Zhongwei, Chen Hu, Zhang Yi

机构信息

Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Department of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

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


DOI:10.18632/oncotarget.5582
PMID:26376680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4741817/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/1303fe2d66f2/oncotarget-06-33961-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/766381e29c1d/oncotarget-06-33961-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/b55a26cce1ec/oncotarget-06-33961-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/d60fa5225545/oncotarget-06-33961-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/6668f3fc8421/oncotarget-06-33961-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/e6f9ca31a29c/oncotarget-06-33961-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/1303fe2d66f2/oncotarget-06-33961-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/766381e29c1d/oncotarget-06-33961-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/b55a26cce1ec/oncotarget-06-33961-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/d60fa5225545/oncotarget-06-33961-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/6668f3fc8421/oncotarget-06-33961-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/e6f9ca31a29c/oncotarget-06-33961-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d12/4741817/1303fe2d66f2/oncotarget-06-33961-g006.jpg

相似文献

[1]
Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis.

Oncotarget. 2015-10-20

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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J Hematol Oncol. 2016-11-25

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[2]
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Front Oncol. 2025-6-18

[3]
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Front Immunol. 2025-3-13

[4]
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Brief Bioinform. 2024-5-23

[5]
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[6]
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Transplant Cell Ther. 2024-2

[7]
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[8]
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Curr Issues Mol Biol. 2023-4-12

[9]
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[10]
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本文引用的文献

[1]
CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells.

Clin Cancer Res. 2015-7-1

[2]
Metaprop: a Stata command to perform meta-analysis of binomial data.

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The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells.

Front Pharmacol. 2014-10-28

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Lancet. 2015-2-7

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N Engl J Med. 2014-10-16

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Blood. 2014-11-13

[7]
Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor.

J Clin Oncol. 2015-2-20

[8]
Antibody-modified T cells: CARs take the front seat for hematologic malignancies.

Blood. 2014-2-27

[9]
Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia.

Sci Transl Med. 2014-2-19

[10]
Dasatinib in combination with fludarabine in patients with refractory chronic lymphocytic leukemia: a multicenter phase 2 study.

Leuk Res. 2013-10-28

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