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.
摘要：
组蛋白去乙酰化酶（HDAC）抑制剂正在成为血液恶性肿瘤的有希望的治疗方法。具有潜在的应用扩展到实体瘤的未来。鉴于其广泛的生物学效应,迫切需要彻底了解与HDAC抑制相关的毒性。在这项研究中,使用FDA不良事件报告系统数据库进行药物警戒分析.通过各种统计方法检测到与HDAC抑制剂相关的可疑不良事件，包括报告赔率比，比例报告比率，信息组件，和经验贝叶斯几何均值。我们的研究结果表明，在报告的所有案件中，胃肠道疾病占队列患者的13%，而淋巴系统疾病占队列的8%，所有这些都表现为HDAC抑制剂诱导的不良事件。重要的是,发现HDAC抑制剂的使用与房颤事件有关，心力衰竭,呼吸衰竭,肝功能障碍,和急性肾损伤。Romidepsin和belinostat与panobinostat和vorinostat相比，表现出更明显的不良事件信号，强调需要对这一特定人群的不良事件进行警惕监测。此外，心房颤动(临床优先评分为7分)是最重要的医学事件,值得临床关注.最终,观察到在治疗开始后的第1个月和第2个月内出现多个不良事件.警惕监测和支持护理策略对于解决与HDAC抑制剂相关的毒性至关重要。特别是那些关于心脏毒性的，呼吸毒性，肾毒性,和肝毒性。
