揭示多发性骨髓瘤中单克隆抗体的心血管和呼吸毒性：来自FDA不良事件报告系统的歧化分析。

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2025-03-17 DOI:10.1007/s00228-025-03824-8

Maria Antonietta Barbieri, Giulia Russo, Giuseppe Cicala, Giuseppe Andò, Tindara Franchina, Nicola Silvestris, Mariacarmela Santarpia, Edoardo Spina

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引用次数: 0

摘要

单克隆抗体（mab）已经彻底改变了多发性骨髓瘤（MM）的治疗，尽管存在潜在的不良事件（ae），但仍显示出显着的有效性。本研究旨在确定MM治疗中与单克隆抗体相关的心血管（CV）和呼吸系统ae的不成比例报告（SDRs）的意外信号。方法：分析2015年1月至2023年12月美国食品药品监督管理局不良事件报告系统（FAERS）数据库中涉及可疑药物（daratumumab、elotuzumab、elranatamab、isatuximab、belantamab mafodotin、teclistamab和talquetamab）的报告。描述性分析之后进行歧化分析，首先比较单克隆抗体与所有其他药物（参照组，RG1），随后进行对其他MM药物（RG2）的敏感性分析。结果：在13,496,241例报告中，31,052例（0.2%）与MM相关，6574例（0.1%）与CV和呼吸不良事件相关，主要涉及老年人(n = 3441；52.3%)和男性(n = 3338；50.8%)患者。不成比例分析确定了daratumumab意想不到的特别提款权，包括心力衰竭(n = 322；Rg1: ror = 4.74, ci 95% = 4.24-5.29；RG2: ROR = 4.42, 95% CI = 3.91-4.99)，栓塞性和血栓性事件，如肺栓塞(162；RG1: 2.44, 2.09-2.85)，深静脉血栓形成(126；RG1: 2.95, 2.47-3.52)，呼吸衰竭(192；Rg1: 4.06, 3.52-4.68；Rg2: 4.2, 3.59-4.91)。Isatuximab与心律失常有关，如心房颤动(46；Rg1: 2.54, 1.9-3.4；RG2: 1.35, 1.01-1.81)，栓塞和血栓事件，包括深静脉血栓形成(26；RG1: 2.93, 1.99-4.3)和肺栓塞(89；Rg1: 6.56, 5.32-8.1；Rg2: 2.93, 2.37-3.63)。Elotuzumab对房颤也有特别的疗效(56；Rg1: 3.68, 2.82-4.79；RG2: 1.96, 1.5-2.56)和深静脉血栓形成(41；Rg1: 5.49, 4.03-7.47)。结论：以往文献中未报道的与临床相关的意外CV和呼吸不良事件，强调了药物警戒的重要性。

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Unveiling cardiovascular and respiratory toxicities with monoclonal antibodies in multiple myeloma: disproportionality analysis from the FDA Adverse Event Reporting System.

Introduction: Monoclonal antibodies (mAbs) have revolutionized the treatment of multiple myeloma (MM), demonstrating remarkable effectiveness, despite potential adverse events (AEs). This study aims to identify unexpected signals of disproportionate reporting (SDRs) for cardiovascular (CV) and respiratory AEs associated with mAbs in MM treatment.

Methods: From January 2015 to December 2023, reports involving suspected drugs (daratumumab, elotuzumab, elranatamab, isatuximab, belantamab mafodotin, teclistamab, and talquetamab) were analyzed in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Descriptive analysis was followed by disproportionality analyses first comparing mAbs to all other drugs (reference group, RG1), and subsequently conducting a sensitivity analysis against other MM drugs (RG2).

Results: Out of 13,496,241 reports, 31,052 (0.2%) were associated with MM, with 6574 (0.1%) linked to CV and respiratory adverse events, primarily involving older population (n = 3441; 52.3%) and male (n = 3338; 50.8%) patients. Disproportionality analyses identified unexpected SDRs for daratumumab, including cardiac failure (n = 322; RG1: ROR = 4.74, CI 95% = 4.24-5.29; RG2: ROR = 4.42, 95% CI = 3.91-4.99), embolic and thrombotic event, such as pulmonary embolism (162; RG1: 2.44, 2.09-2.85), deep vein thrombosis (126; RG1: 2.95, 2.47-3.52), and respiratory failure (192; RG1: 4.06, 3.52-4.68; RG2: 4.2, 3.59-4.91). Isatuximab was linked to cardiac arrhythmia, such as atrial fibrillation (46; RG1: 2.54, 1.9-3.4; RG2: 1.35, 1.01-1.81), embolic and thrombotic event, including deep vein thrombosis (26; RG1: 2.93, 1.99-4.3) and pulmonary embolism (89; RG1: 6.56, 5.32-8.1; RG2: 2.93, 2.37-3.63). Elotuzumab showed also SDRs for atrial fibrillation (56; RG1: 3.68, 2.82-4.79; RG2: 1.96, 1.5-2.56) and deep vein thrombosis (41; RG1: 5.49, 4.03-7.47).

Conclusion: Unexpected CV and respiratory AEs with clinical relevance not previously reported in literature have been identified underlining the importance of pharmacovigilance.

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.