Case Report: Sudden very late-onset near fatal PD1 inhibitor-associated myocarditis with out-of-hospital cardiac arrest after >2.5 years of pembrolizumab treatment

Richard I Lewis; Katharina Seuthe; Simon Lennartz; Jan-Phillip Weber; Nicole Kreuzberg; Karin Klingel; Paul J Bröckelmann

doi:10.3389/fcvm.2024.1328378

Case Report: Sudden very late-onset near fatal PD1 inhibitor-associated myocarditis with out-of-hospital cardiac arrest after >2.5 years of pembrolizumab treatment

Front Cardiovasc Med. 2024 Feb 19:11:1328378. doi: 10.3389/fcvm.2024.1328378. eCollection 2024.

Authors

Richard I Lewis¹, Katharina Seuthe², Simon Lennartz³, Jan-Phillip Weber⁴, Nicole Kreuzberg⁵, Karin Klingel⁶, Paul J Bröckelmann¹

Affiliations

¹ Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
² Department III of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
³ Department of Radiology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
⁴ Center for Hematology and Oncology, Oncology Cologne, Cologne, Germany.
⁵ Department of Dermatology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.
⁶ Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany.

Abstract

Introduction: Immune checkpoint inhibitors have advanced the outcomes of many different types of cancer. A rare but extraordinarily severe complication of these agents resembles immune checkpoint inhibitor-related myocarditis, which typically occurs within the first few weeks after treatment initiation with a mortality of 25%-50%.

Case report: A 57-year-old woman had uneventfully received pembrolizumab for metastatic non-small cell lung cancer for over 2.5 years and was admitted after an out-of-hospital cardiac arrest due to ventricular fibrillation. After successful cardiopulmonary resuscitation, the initial diagnostic work-up showed elevated cardiac enzymes and a limited left-ventricular ejection fraction, while coronary angiography did not show relevant stenosis. Despite cardiac MRI being unsuggestive of myocarditis, myocardial biopsies were obtained and histologically confirmed anti-PD-1 antibody-associated myocarditis. After the initiation of prednisone at 1 mg/kg body weight, the patient gradually recovered and was discharged three weeks later with markedly improved cardiac function.

Conclusion: This case resembles the first description of a very late onset irMyocarditis, occurring over 2.5 years after the start of treatment. It demonstrates the importance of contemplating that severe immune-related toxicities with a sudden onset clinical presentation may occur even after long uneventful periods of anti-PD-1 immune checkpoint inhibitor treatment. Furthermore, it underlines the critical importance of myocardial biopsies in this setting, especially when cardiac MRI remains inconclusive. Moreover, it demonstrates the necessity and benefits of early immunosuppressive treatment if immune-related myocarditis is considered a differential diagnosis.

Keywords: cancer immunotherapy; immune checkpoint inhibition; immune related adverse effects (irAEs); immune-related myocarditis; pembrolizumab.

Publication types

Case Reports

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article.