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Review Article

Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety

[ Vol. 26 , Issue. 17 ]

Author(s):

Lu Hao, Tongtong Li, Lung-Ji Chang* and Xiaochuan Chen*   Pages 3068 - 3079 ( 12 )

Abstract:


Background: Adoptive infusion of chimeric antigen receptor transduced T- cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results.

Objective: In this report, we performed a meta-analysis to evaluate the efficacy and side effects of CAR-T on refractory and/or relapsed B-cell malignancies, including leukemia and lymphoma.

Methods: Clinical studies investigating efficacy and safety of CAR-T in acute and chronic lymphocytic leukemia and lymphoma were identified by searching PubMed and EMBASE. Outcomes of efficacy subjected to analysis were the rates of complete remission (CR) and partial remission (PR). The safety parameters were the prevalence of adverse effects including fever, hypotension, and acute renal failure. Meta analyses were performed using R software. Weighted hazard ratio (HR) with 95% confidence intervals was calculated for each outcome. Fixed or random-effects models were employed depending on the heterogeneity across the included studies.

Results: Nineteen published clinical studies with a total of 391 patients were included for the meta-analysis. The pooled rate of complete remission was 55% (95% CI 41%-69%); the pooled rate of partial remission was 25% (95% CI: 19%-33%). The prevalence of fever was 62% (95% CI: 41%-79%), the hypotension was 22% (95% CI: 15%-31%), and the acute renal failure was 24% (95% CI: 16%-34%). All adverse effects were manageable and no death was reported due to toxicity.

Conclusion: CD19-targeted CAR-T is an effective modality in treating refractory B-cell malignancies including leukemia and lymphoma. However, there is still a need to develop strategies to improve the safety in its clinical use.

Keywords:

Chimeric antigen receptor, adoptive T cell therapy, B-cell malignancies, leukemia, lymphoma, safety.

Affiliation:

Shenzhen Geno-Immune Medical Institute, Shenzhen 518057, Clinical Medicine Program, Nanchang University Medical College, Nanchang 330006, Shenzhen Geno-Immune Medical Institute, Shenzhen 518057, Shenzhen Geno-Immune Medical Institute, Shenzhen 518057



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