Al-Yafeai Zaki, Ghoweba Mohamed, Ananthaneni Anil, Abduljabar Hamzah, Aziz David
Department of Internal Medicine, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
Department of Internal Medicine, CHRISTUS Good Shepherd/Texas A&M College of Medicine, Longview, TX, USA.
Br J Clin Pharmacol. 2023 Feb;89(2):641-648. doi: 10.1111/bcp.15499. Epub 2022 Sep 9.
Multiple myeloma accounts for over 10-15% of haematological malignancies. Continued molecular advances have resulted in the development of new drugs for treatment of multiple myeloma. Four drugs were approved by the Food and Drug Administration (FDA) in 2015, but their safety is not well defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs.
We reviewed the adverse cardiac events of newly approved FDA drugs since 2015 using the US FDA Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval (CIs) for the drugs that have the highest incidence of cardiovascular adverse events.
Among the medications that have approved for multiple myeloma between 2015 and 2020, 4 novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, ixazomib, daratumumab and panobinostat compared to other FAERS drugs was 5.8 (4.4-7.7), 1.9 (1.5-2.3), 4.8 (4.2-5.6) and 5.7 (4.1-8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4-10.5), 4.7 (4.1-5.4), 5.8 (4.9-6.7) and 5.6 (3.8-8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9-3.9), 2.7 (2.3-3.2), 2.3 (1.9-2.8) and 4.6 (3.2-6.6) due to elotuzumab, ixazomib, daratumumab and panobinostat compared to all other drugs in FAERS.
Our results demonstrated that certain newly approved antimyeloma therapies are significantly associated with previously unknown cardiotoxicity. These results warrant further studies and highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.
多发性骨髓瘤占血液系统恶性肿瘤的10 - 15%以上。分子研究的不断进展促使了用于治疗多发性骨髓瘤的新药的开发。2015年美国食品药品监督管理局（FDA）批准了四种药物，但它们的安全性尚未明确界定。本研究的目的是描述这些药物的心血管不良事件。
我们使用美国FDA不良事件报告系统（FAERS）数据库回顾了自2015年以来FDA新批准药物的心脏不良事件。我们计算了心血管不良事件发生率最高的药物的报告比值比（ROR）及其95%置信区间（CI）。
在2015年至2020年期间获批用于多发性骨髓瘤的药物中，4种新药显示出最高的心脏毒性发生率。与其他FAERS药物相比，埃罗妥珠单抗、伊沙佐米、达雷妥尤单抗和帕比司他导致房颤的ROR（95%CI）分别为5.8（4.4 - 7.7）、1.9（1.5 - 2.3）、4.8（4.2 - 5.6）和5.7（4.1 - 8.1）。与FAERS中的所有其他药物相比，埃罗妥珠单抗、伊沙佐米、达雷妥尤单抗和帕比司他导致心力衰竭的ROR（95%CI）分别为8.2（6.4 - 10.5）、4.7（4.1 - 5.4）、5.8（4.9 - 6.7）和5.6（3.8 - 8.1），导致冠心病的ROR（95%CI）分别为2.7（1.9 - 3.9）、2.7（2.3 - 3.2）、2.3（1.9 - 2.8）和4.6（3.2 - 6.6）。
我们的结果表明，某些新批准的抗骨髓瘤疗法与先前未知的心脏毒性显著相关。这些结果值得进一步研究，并突出了在使用这些新型药物时考虑多发性骨髓瘤患者心脏病史的重要性。
