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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1400101
This article is part of the Research Topic A silent Threat: Novel Treatments and Therapies to Prevent Cancer Treatment-Induced Cardiotoxicity View all articles

Cardiovascular adverse events associated with targeted therapies for multiple myeloma: A pharmacovigilance study Brief Title: Cardiovascular AEs in MM-targeted therapy

Provisionally accepted
Yanli Zhang Yanli Zhang 1Chang Shan Chang Shan 1Xinxin Zhang Xinxin Zhang 1Ying Liu Ying Liu 1*Yun L. Xia Yun L. Xia 1*Yanfeng Wang Yanfeng Wang 2*
  • 1 First Affiliated Hospital, Dalian Medical University, Dalian, China
  • 2 Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    Multiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated.This study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs).Disproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs)A total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after one year. This trend was observed for all cardiovascular AEs. The Kaplan-Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab (P<0.001).MM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management.

    Keywords: Multiple Myeloma, Cardio-oncology, Cardiovascular adverse event, targeted therapy, Cardiovascular safety

    Received: 13 Mar 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Zhang, Shan, Zhang, Liu, Xia and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ying Liu, First Affiliated Hospital, Dalian Medical University, Dalian, China
    Yun L. Xia, First Affiliated Hospital, Dalian Medical University, Dalian, China
    Yanfeng Wang, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, Beijing Municipality, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.