Department of Pharmacy, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Expert Opin Drug Saf. 2024 May;23(5):581-591. doi: 10.1080/14740338.2024.2328321. Epub 2024 Apr 10.
Daratumumab, a first-in-class humanized IgG1κ monoclonal antibody that targets the CD38 epitope, has been approved for treatment of multiple myeloma by FDA. The current study was to evaluate daratumumab-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).
Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of daratumumab-associated AEs.
Out of 10,378,816 reports collected from the FAERS database, 8727 reports of daratumumab-associated AEs were identified. A total of 183 significant disproportionality preferred terms (PTs) were retained. Unexpected significant AEs such as meningitis aseptic, leukoencephalopathy, tumor lysis syndrome, disseminated intravascular coagulation, hyperviscosity syndrome, sudden hearing loss, ileus and diverticular perforation were also detected. The median onset time of daratumumab-related AEs was 11 days (interquartile range [IQR] 0-76 days), and most of the cases occurred within 30 days.
Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship.
达雷妥尤单抗是一种针对 CD38 表位的首创人源化 IgG1κ 单克隆抗体，已被美国食品药品监督管理局（FDA）批准用于多发性骨髓瘤的治疗。本研究旨在通过美国食品药品监督管理局不良事件报告系统（FAERS）的数据挖掘，评估达雷妥尤单抗相关不良事件（AE）。
采用不稳定性分析，包括报告比值比（ROR）、比例报告比值（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项伽马泊松收缩器（MGPS）算法，来量化达雷妥尤单抗相关 AE 的信号。
从 FAERS 数据库中收集的 10378816 份报告中，确定了 8727 份与达雷妥尤单抗相关的 AE 报告。共保留了 183 个显著的不稳定性首选术语（PT）。还检测到一些意外的显著 AE，如无菌性脑膜炎、脑白质病、肿瘤溶解综合征、弥漫性血管内凝血、高粘滞综合征、突发性听力损失、肠梗阻和憩室穿孔。达雷妥尤单抗相关 AE 的中位发病时间为 11 天（四分位距[IQR]0-76 天），大多数病例发生在 30 天内。
本研究发现了达雷妥尤单抗的潜在新的和意外的 AE 信号，表明需要进行前瞻性临床研究来证实这些结果并阐明它们之间的关系。
