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Cardiotoxicities of novel cancer immunotherapies
  1. Ashley F Stein-Merlob1,
  2. Michael V Rothberg2,
  3. Antoni Ribas3,
  4. Eric H Yang4
  1. 1 Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
  2. 2 University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA
  3. 3 Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
  4. 4 UCLA-Cardio-Oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
  1. Correspondence to Dr Ashley F Stein-Merlob, UCLA Division of Cardiology, Department of Medicine 650 Charles E Young Drive South, University of California at Los Angeles, Los Angeles, CA, USA; asteinmerlob{at}mednet.ucla.edu

Abstract

Immunotherapy revolutionised oncology by harnessing the native immune system to effectively treat a wide variety of malignancies even at advanced stages. Off-target immune activation leads to immune-related adverse events affecting multiple organ systems, including the cardiovascular system. In this review, we discuss the current literature describing the epidemiology, mechanisms and proposed management of cardiotoxicities related to immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers. ICIs are monoclonal antibody antagonists that block a co-inhibitory pathway used by tumour cells to evade a T cell-mediated immune response. ICI-associated cardiotoxicities include myocarditis, pericarditis, atherosclerosis, arrhythmias and vasculitis. ICI-associated myocarditis is the most recognised and potentially fatal cardiotoxicity with mortality approaching 50%. Recently, ICI-associated dysregulation of the atherosclerotic plaque immune response with prolonged use has been linked to early progression of atherosclerosis and myocardial infarction. Treatment strategies include immunosuppression with corticosteroids and supportive care. In CAR T-cell therapy, autologous T cells are genetically engineered to express receptors targeted to cancer cells. While stimulating an effective tumour response, they also elicit a profound immune reaction called cytokine release syndrome (CRS). High-grade CRS causes significant systemic abnormalities, including cardiovascular effects such as arrhythmias, haemodynamic compromise and cardiomyopathy. Treatment with interleukin-6 inhibitors and corticosteroids is associated with improved outcomes. The evidence shows that, although uncommon, immunotherapy-related cardiovascular toxicities confer significant risk of morbidity and mortality and benefit from rapid immunosuppressive treatment. As new immunotherapies are developed and adopted, it will be imperative to closely monitor for cardiotoxicity.

  • cardiomyopathies
  • myocarditis
  • drug monitoring
  • diagnostic imaging

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Footnotes

  • Twitter @A_SteinMerlob, @mvrothberg, @datsunian

  • Contributors All authors significantly contributed to manuscript design, planning, writing, visual design and editing and revision.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests EY reports receiving research funding from CSL Behring (non-relevant). AFS-M is supported by the National Institutes of Health Cardiovascular Scientist Training Program (T32 HL007895). MVR has no conflicts of interest to report. AR has received honoraria from consulting with Amgen, Bristol-Myers Squibb, Chugai, Genentech, Merck, Novartis, Roche, Sanofi and Vedanta, is or has been a member of the scientific advisory board and holds stock in Advaxis, Apricity, Arcus, Compugen, CytomX, Five Prime, Highlight, ImaginAb, Isoplexis, Kalthera, Kite-Gilead, Merus, PACT Pharma, RAPT, Rgenix and Tango, has received research funding from Agilent and from Bristol-Myers Squibb through Stand Up to Cancer (SU2C).

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Author note Additional references w1–8 can be found in online supplemental file 1.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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