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

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Author(s): Lu Hao, Tongtong Li, Lung-Ji Chang*, Xiaochuan Chen.

Journal Name: Current Medicinal Chemistry

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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(CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results.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 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%); 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 acute and chronic lymphatic leukemia, Hodjkin’s and non-Hodjkin’s lymphoma.

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

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(E-pub Ahead of Print)
DOI: 10.2174/0929867324666170801101842
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