利用单克隆抗体揭示多发性骨髓瘤中的心血管和呼吸系统毒性：来自美国食品药品监督管理局不良事件报告系统的不成比例分析
Unveiling cardiovascular and respiratory toxicities with monoclonal antibodies in multiple myeloma: disproportionality analysis from the FDA Adverse Event Reporting System.
作者信息
Barbieri Maria Antonietta, Russo Giulia, Cicala Giuseppe, Andò Giuseppe, Franchina Tindara, Silvestris Nicola, Santarpia Mariacarmela, Spina Edoardo
机构信息
Department of Clinical and Experimental Medicine, University of Messina, 98125, Messina, Italy.
Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, 98125, Messina, Italy.
出版信息
Eur J Clin Pharmacol. 2025 May;81(5):755-770. doi: 10.1007/s00228-025-03824-8. Epub 2025 Mar 17.
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.
引言
单克隆抗体（mAbs）彻底改变了多发性骨髓瘤（MM）的治疗方式，尽管存在潜在不良事件（AE），但仍显示出显著疗效。本研究旨在确定MM治疗中与mAbs相关的心血管（CV）和呼吸系统AE不成比例报告的意外信号（SDRs）。
方法
2015年1月至2023年12月，在美国食品药品监督管理局不良事件报告系统（FAERS）数据库中分析了涉及可疑药物（达雷妥尤单抗、埃罗妥珠单抗、伊拉纳单抗、isatuximab、贝兰他单抗莫福汀、替西妥单抗和talquetamab）的报告。进行描述性分析后进行不成比例分析，首先将mAbs与所有其他药物进行比较（参考组，RG1），随后针对其他MM药物进行敏感性分析（RG2）。
结果
在13496241份报告中，31052份（0.2%）与MM相关，6574份（0.1%）与CV和呼吸系统不良事件相关，主要涉及老年人群（n = 3441；52.3%）和男性患者（n = 3338；50.8%）。不成比例分析确定了达雷妥尤单抗的意外SDRs，包括心力衰竭（n = 322；RG1：风险比（ROR）= 4.74，95%置信区间（CI）= 4.24 - 5.29；RG2：ROR = 4.42，95% CI = 3.91 - 4.99）、栓塞和血栓形成事件，如肺栓塞（162例；RG1：2.44，2.09 - 2.85）、深静脉血栓形成（126例；RG1：2.95，2.47 - 3.52）和呼吸衰竭（192例；RG1：4.06，3.52 - 4.68；RG2：4.2，3.59 - 4.91）。Isatuximab与心律失常相关，如心房颤动（46例；RG1：2.54，1.9 - 3.4；RG2：1.35，1.01 - 1.81）、栓塞和血栓形成事件，包括深静脉血栓形成（26例；RG1：2.93，1.99 - 4.3）和肺栓塞（89例；RG1：6.56，5.32 - 8.1；RG2：2.93，2.37 - 3.63）。埃罗妥珠单抗也显示出心房颤动（56例；RG1：3.68，2.82 - 4.79；RG2：1.96，1.5 - 2.56）和深静脉血栓形成（41例；RG1：5.49，4.03 - 7.47）的SDRs。
结论
已识别出文献中先前未报道的具有临床相关性的意外CV和呼吸系统AE，强调了药物警戒的重要性。
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