Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.
International Research Center for Precision Medicine, Transformative Technology and Software Services, Changsha, China.
Clin Pharmacol Ther. 2023 Jul;114(1):211-219. doi: 10.1002/cpt.2920. Epub 2023 May 11.
Although some tumor lysis syndrome (TLS) cases have been reported with patients with multiple myeloma (MM) taking monoclonal antibodies (mAbs), the association between TLS and mAbs remains mostly unknown. We aim to investigate the association between TLS and mAbs and describe clinical features. We conducted a disproportionality analysis to investigate the link between mAbs and TLS by excluding known confounders and compared with other anticancer drugs. The association between mAbs and TLS was evaluated using information component (IC). Drug-drug interaction signals were calculated based on the Ω shrinkage measure. Parametric distribution with the goodness-of-fit test was used for the reported time-to-onset analysis. From 2016 Q1, to 2022 Q4, a total of 274 TLS with mAbs were reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. There were 27% of patients with TLS with mAbs who died and 20.1% occurred a life-threatening situation. Daratumumab, elotuzumab, and belantamab mafodotin presented a robust disproportionate signal of TLS after excluding known confounders (IC > 0). Daratumumab had the highest disproportionate signal of TLS among all anticancer drugs for MM. Reported time-to-onset analysis showed the median days for TLS with daratumumab, isatuximab, elotuzumab, and belantamab mafodotin were 1.5, 14.5, 5.5, and 5.5 days, respectively. The drug-drug interaction analysis showed the co-administration of drugs known to increase urate, induce hyperkalemia, or hypocalcemia elevated the reporting frequency for TLS with mAbs (Ω > 0). Our postmarketing pharmacovigilance analysis detected the reporting association of TLS and mAbs in patients with MM. Additional studies with robust epidemiological study designs that can validate these findings are warranted.
尽管已有报道称多发性骨髓瘤（MM）患者在使用单克隆抗体（mAbs）时会发生肿瘤溶解综合征（TLS），但 TLS 与 mAbs 之间的关联仍知之甚少。我们旨在调查 TLS 与 mAbs 之间的关联，并描述其临床特征。我们通过排除已知混杂因素进行了一项不成比例分析，以调查 mAbs 与 TLS 之间的联系，并与其他抗癌药物进行了比较。使用信息成分（IC）评估 mAbs 与 TLS 之间的关联。基于Ω收缩度量计算药物-药物相互作用信号。根据拟合优度检验进行参数分布以用于报告的发病时间分析。从 2016 年第 1 季度到 2022 年第 4 季度，美国食品和药物管理局不良事件报告系统（FAERS）数据库共报告了 274 例使用 mAbs 的 TLS 病例。有 27%的 mAbs 相关 TLS 患者死亡，20.1%发生危及生命的情况。排除已知混杂因素后，达雷妥尤单抗、埃罗妥珠单抗和贝兰他单抗mafodotin 呈现出与 TLS 不成比例的强烈信号（IC > 0）。在所有用于 MM 的抗癌药物中，达雷妥尤单抗与 TLS 的不成比例信号最高。报告的发病时间分析显示，达雷妥尤单抗、伊沙妥昔单抗、埃罗妥珠单抗和贝兰他单抗 mafodotin 发生 TLS 的中位时间分别为 1.5、14.5、5.5 和 5.5 天。药物-药物相互作用分析表明，联合使用已知能增加尿酸、引起高钾血症或低钙血症的药物会增加 mAbs 相关 TLS 的报告频率（Ω > 0）。我们的上市后药物警戒分析检测到 MM 患者中 TLS 与 mAbs 的报告关联。需要进行具有稳健的流行病学研究设计的额外研究来验证这些发现。
