Abstract
Histone deacetylase (HDAC) inhibitors are emerging as promising treatments for hematological malignancies, with potential applications extending to solid tumors in the future. Given their wide-ranging biological effects, there is a pressing need for a thorough understanding of the toxicities linked to HDAC inhibition. In this study, a pharmacovigilance analysis was conducted using the FDA Adverse Event Reporting System database. Suspected adverse events linked to HDAC inhibitors were detected through various statistical methodologies, including reporting odds ratio, proportional reporting ratio, information component, and Empirical Bayes Geometric Mean. Our study findings have illuminated that, among the total reported cases examined, gastrointestinal disorders accounted for 13% patients of the cohort, while lymphatic system disorders comprised 8% cases of the cohort, all of which manifested as adverse events induced by HDAC inhibitors. Importantly, the usage of HDAC inhibitors was found to be associated with incidents of atrial fibrillation, heart failure, respiratory failure, hepatic dysfunction, and acute kidney injury. Romidepsin and belinostat demonstrated more pronounced signals of adverse events compared to panobinostat and vorinostat, emphasizing the need for vigilant monitoring of adverse events in this particular population. Furthermore, atrial fibrillation (clinical priority score of 7 points) emerged as the paramount medical event warranting utmost clinical attention. Eventually, multiple adverse events were observe to emerge within the initial and second months following the initiation of treatment. Vigilant monitoring and supportive care strategies are critical in addressing the toxicities associated with HDAC inhibitors, particularly those concerning cardiotoxicity, respiratory toxicity, renal toxicity, and hepatotoxicity.
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Data availability
No datasets were generated or analysed during the current study.
Abbreviations
- AEs:
-
Adverse events
- CTL:
-
Cutaneous T-cell lymphoma
- EBGM:
-
Empirical Bayes Geometric Mean
- EMA:
-
European Medicines Agency
- FDA:
-
United States Food and Drug Administration
- FAERS:
-
FDA Adverse Event Reporting System
- HDACs:
-
Histone deacetylases
- IC:
-
Information component
- MM:
-
Multiple myeloma
- PTL:
-
Peripheral T-cell lymphoma
- PRR:
-
Proportional reporting ratio
- PT:
-
Preferred term
- ROR:
-
Reporting odds ratio
- SOCs:
-
System organ classes
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Acknowledgements
We appreciate the work of the FAERS database (https://www.fda.gov/).
Funding
This work was supported by the Science and Technology Program of Guangzhou, China (202102080498 to W. Wang).
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Wenjie Li & YiMing Fu: Conceptualization, methodology, data curation, software and writing-review & editing. Wei Wang: Funding acquisition, project administration, supervision and validation. The work reported in the paper has been performed by the authors, unless clearly specified in the text.
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Highlights
(1) Neglected post-marketing research on HDAC inhibitors prompts pharmacovigilance analysis.
(2) Our Study finds gastrointestinal disorders and lymphatic system disorders as major AEs.
(3) HDAC inhibitors link to atrial fibrillation, heart/respiratory failure, hepatic dysfunction, kidney injury.
(4) Romidepsin and belinostat show stronger signals of adverse events; vigilant monitoring imperative.
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Li, W., Fu, Y. & Wang, W. A real-world pharmacovigilance study investigating the toxicities of histone deacetylase inhibitors. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05691-2
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DOI: https://doi.org/10.1007/s00277-024-05691-2