Li Dan, Zhang Yuan, Ni Jia Qi, Zhu Juan, Lu Wen Ting, Chen Ya Lin, Cheng Lei, Wang Yu Qi, Li Qian Jiang, Wang Jie, Lu Yan Bing, Chen Jia, Chen Li
Zhejiang Provincial People's Hospital Bijie Hospital, Bijie, Guizhou, China.
West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Pharmacol. 2024 May 13;15:1372401. doi: 10.3389/fphar.2024.1372401. eCollection 2024.
Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time. Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.
苯达莫司汀被批准用于治疗慢性淋巴细胞白血病和惰性B细胞非霍奇金淋巴瘤。尽管其具有治疗益处，但苯达莫司汀在大量人群中的长期安全性仍未得到充分了解。本研究使用真实世界药物警戒数据库评估与苯达莫司汀相关的不良事件（AE），以支持其临床应用。我们进行了一项上市后风险分析，以评估苯达莫司汀与其不良事件之间的关联。数据从美国食品药品监督管理局（FDA）的不良事件报告系统（FAERS）中提取，涵盖2017年1月至2023年9月期间。进一步分析了苯达莫司汀相关不良事件的特征和发病时间。使用MYSQL 8.0、Navicat Premium 15、Microsoft EXCEL 2016和Minitab 21.0进行统计分析。从FAERS数据库中收集了9,461,874份报告，其中9,131份将苯达莫司汀确定为“主要疑似”药物。我们确定了331个显著不成比例的首选术语（PT）。常见的不良事件包括发热、中性粒细胞减少、输液部位反应、进行性多灶性白质脑病（PML）、注射部位血管炎和肺炎——所有这些都记录在苯达莫司汀的标签上。值得注意的是，发现了16种意外且显著的不良事件，包括低丙种球蛋白血症，鉴于其在苯达莫司汀治疗后可能增加感染易感性，这令人担忧。其他显著发现包括过敏反应、PML和皮肤恶性肿瘤，表明可能需要更新该药物的标签。医生应监测患者的神经和皮肤变化，如果怀疑患有PML应停止治疗。此外，苯达莫司汀相关不良事件的中位发病时间为13天，四分位间距[IQR]为0 - 59天，主要发生在开始治疗后的第一天。苯达莫司汀相关不良事件的β值表明风险随时间降低。我们的研究发现了一些与苯达莫司汀相关的潜在药物警戒信号，为其安全有效的临床应用提供了重要见解。
