A real-world pharmacovigilance study investigating the toxicities of histone deacetylase inhibitors.

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.