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Preliminary assessment of cardiotoxicity in chimeric antigen receptor T cell therapy: a systematic review and meta-analysis

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Abstract

As a novel anticancer therapy, chimeric antigen receptor T (CAR T) cell therapy may lead to cardiotoxic reactions. However, the exact incidence remains unclear. Our study aimed to preliminarily assess the prevalence of cardiotoxicity after CAR T cell treatment using a systematic review and meta-analysis. PubMed, Embase, Web of Science, and Cochrane databases were searched for potentially relevant studies. All types of relevant clinical studies were screened and assessed for risk bias. In most instances, random-effect models were used for data analysis, and heterogeneity between studies was evaluated. Standard quality assessment tools were used to assess quality. The study was registered with PROSPERO (CRD42022304611). Eight eligible studies comprising 3567 patients, including seven observational studies and one controlled study, were identified. The incidence of cardiovascular events was 16.7% [95% confidence interval (CI) 0.138–0.200, P < 0.01)]. Arrhythmia was the most common disorder, with an incidence of 6.5% (95% CI 0.029–0.115, P < 0.01). The occurrence of cardiotoxicity was associated with cytokine release syndrome (CRS), with a prevalence of 18.7% (95% CI 0.107–0.315, P < 0.01). Moreover, such adverse reactions were more common when CRS > 2 (OR = 0.07, 95% CI 0.02–0.29, P < 0.01). The risk of cardiotoxicity was not notably higher in patients receiving CAR T cell therapy than in those receiving traditional anticancer treatment. However, sufficient attention should be paid to this. And further evidence from large-scale clinical trials are needed.

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Availability of data and materials

The datasets generated and analysed during the current study are available in scientific databases.

Abbreviations

CAR T:

Chimeric antigen receptor T

ICIs:

Immune checkpoint inhibitors

HF:

Heart failure

FDA:

The Food and Drug Administration

MINORS:

The methodological index for non-randomized studies

CRS:

Cytokine release syndrome

OR:

Odds Ratio

SE:

Standard Error

CI:

Confidence Interval

ALL:

Acute lymphoblastic lymphoma

DLBCL:

Diffuse large B-cell lymphoma

Tisa:

Tisagenlecleucel

Axi-cel:

Axicabtagene ciloleucel

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Acknowledgements

We thank all the researchers for their contributions to this study.

Funding

This study was funded by grants from the Xuzhou Science and Technology Bureau to Defeng Pan [Grant Number: KC20097] and Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX21_2671].

Author information

Author notes

  1. Minjia Guo and Xiaotong Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, 221004, Jiangsu, China

    Minjia Guo, Xiaotong Wang, Aili Liu, Tao Xu, Chunyan Huan, Hong Zhu & Defeng Pan

  2. Department of General Practice, The Affiliated Hospital of Xuzhou Medical University, 99 Huaihai West Road, Xuzhou, 221004, Jiangsu, China

    Huimin Wu, Yue Hu & Shuaishuai Zhou

  3. Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China

    Shengjue Xiao

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  1. Minjia Guo
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Contributions

DP, HZ, MG, and XW participated in the design and execution of the study and drafted the manuscript. AL and SX conducted literature search to screen eligible studies. TX and CH extracted data and performed statistical analyses. HW, YH, and SZ analysed and interpreted the results. All authors have rigorously reviewed the essential elements of the report and approved the final version of the manuscript. The authors contributed equally to this work.

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Correspondence to Hong Zhu or Defeng Pan.

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Guo, M., Wang, X., Xiao, S. et al. Preliminary assessment of cardiotoxicity in chimeric antigen receptor T cell therapy: a systematic review and meta-analysis. Clin Exp Med 23, 2041–2050 (2023). https://doi.org/10.1007/s10238-023-01042-z

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