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Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study

Cancer Gene Therapy (2024)Cite this article

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Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has achieved durable response in patients with hematological malignancies, however, therapy-associated multisystem toxicities are commonly observed. Here, we systematically analyzed CAR-T-related gastrointestinal adverse events (GAEs) using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC). Among 105,087,611 reports in FAERS, 1518 CAR-T-related GAEs reports were identified. 23 GAEs (n = 281, 18.51%) were significantly overreported following CAR-T therapy compared with the full database, of which 11 GAEs (n = 156, 10.28%) were associated with gastrointestinal infections (GI), such as clostridium difficile colitis (n = 44 [2.90%], ROR = 5.55), enterovirus infection (n = 23 [1.52%], ROR = 20.02), and mucormycosis (n = 15 [0.99%], ROR = 3.09). Overall, the fatality rate of 11 GI-related AEs was 29.49%, especially mucormycosis causing substantial mortality with 60%. In addition, 4 of 23 overreported GAEs were related to haemorrhage and the mortality of gastrointestinal haemorrhage was 73.17%. Lastly, 29 death-related GAEs were identified. These findings could help clinicians early alert those rarely reported but lethal GAEs, thus reducing the risk of severe toxicities.

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Fig. 1: Overall comparations of CAR-T-related GAEs and GAEs-associated mortality among different CAR-T products.
Fig. 2: Comparation of various concurrent GAEs with death reports between axi-cel and tisagenlecleucel.
Fig. 3: Comparation of the occurrence of GAEs among different groups and overlap between GAEs and CRS or HGG.
Fig. 4: Number of reports of 11 GI-associated adverse events and corresponding fatality rates (number of reported deaths/reported adverse events).

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Data availability

This study was performed based on the data from Food and Drug Administration adverse event reporting system (FAERS), a publicly available and anonymized database (https://www.fda.gov/regulatory-information/freedom-information).

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Acknowledgements

The authors thank all the participants and information uploaders in the FAERS.

Funding

J Yang received funding from the National Natural Science Foundation of China (81770209, 82270202) and Shanghai 2021 “Action Plan of Technological Innovation” Biomedical Science and Technology Support Special Project (21S11906100). J Chen received funding from the National Natural Science Foundation of China (81970178). N Liu received funding from the National Natural Science Foundation of China (82100162). Y Wang received funding from the National Natural Science Foundation of China (82300257). Y Wang received funding from the Youth Start-up Foundation of the First Affiliated Hospital of Second Military Medical University (2020QNB03, 2022QN067).

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  1. These authors contributed equally: Zhiqiang Song, Yang Wang, Ping Liu.

Authors and Affiliations

  1. Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Zhiqiang Song, Yang Wang, Ping Liu, Yuke Geng, Na Liu, Jie Chen & Jianmin Yang

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Contributions

Na Liu, Jie Chen, Jianmin Yang: Conceptualization, Methodology, Software; Zhiqiang Song, Yang Wang, Ping Liu: Data curation, Visualization, Investigation, Writing-Original draft preparation; Jianmin Yang: Supervision; Zhiqiang Song, Yang Wang, Yuke Geng: Software, Validation; Na Liu, Jie Chen, Jianmin Yang: Writing-Reviewing and Editing.

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Correspondence to Na Liu, Jie Chen or Jianmin Yang.

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Song, Z., Wang, Y., Liu, P. et al. Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00752-0

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