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Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis

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Abstract

Background

Immune checkpoint inhibitors (ICI) have transformed the standard care of cancer treatment. Recent case reports describe ICI-mediated myocarditis with an atypical presentation and fatal potential which lead to permanent interruption of immunotherapy.

Objectives

To characterize ICI-mediated myocarditis and re-introduction to immunotherapy.

Methods

During 2019, 849 patients were treated with ICI at Tel Aviv Sourasky Medical Center for the diagnosis of lung adenocarcinoma, gastric adenocarcinoma, urothelial carcinoma, and hepatocellular carcinoma. Overall, seven (0.8%) patients were diagnosed with ICI-mediated myocarditis, according to the European Society of Cardiology guidelines of myocarditis 2013. We retrospectively evaluated their presentation, severity, and clinical outcomes.

Results

Among the seven patients, only one had a history of cardiac disease. The majority were diagnosed with lung adenocarcinoma and treated with anti-programmed death-1 antibody. All patients were treated with single-agent ICI. Most patients presented with cardiac symptoms, elevated troponin and typical cardiac magnetic resonance; however, only three had reduced ejection fraction. Overall, three patients were chosen for re-introduction with concomitant low dose steroids and weekly troponin follow-up. Two patients diagnosed with grade I and II renewed therapy successfully with no recurrence of symptoms and improvement in disease burden. The one patient diagnosed with grade III developed worsening of cardiac symptoms after the 1st cycle and, therefore, therapy was interrupted permanently.

Conclusions

ICI-mediated myocarditis is potentially fatal and leads to permanent interruption of life-saving cancer therapy. The current data suggest that re-introduction may be considered in low-grade patients; however, a better definition of the diagnosis and grading is needed.

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Authors and Affiliations

  1. Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

    Shira Peleg Hasson, Sivan Shamai, Ravit Geva, Ofer Merimsky, Ari Raphael & Ido Wolf

  2. Department of Cardiology, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel

    Haim Shmilovich, Zach Rozenbaum & Michal Laufer-Perl

  3. Department of Pediatric Cardiology Unit, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel

    livia Kapusta & Michal Laufer-Perl

  4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Shira Peleg Hasson, Benjamin Salwen, Ayelet Sivan, Sivan Shamai, Ravit Geva, Ofer Merimsky, Ari Raphael, Haim Shmilovich, Yonatan Moshkovits, livia Kapusta, Zach Rozenbaum & Ido Wolf

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  1. Shira Peleg Hasson
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  2. Benjamin Salwen
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  3. Ayelet Sivan
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Correspondence to Michal Laufer-Perl.

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Peleg Hasson, S., Salwen, B., Sivan, A. et al. Re-introducing immunotherapy in patients surviving immune checkpoint inhibitors-mediated myocarditis. Clin Res Cardiol 110, 50–60 (2021). https://doi.org/10.1007/s00392-020-01648-3

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  • DOI: https://doi.org/10.1007/s00392-020-01648-3

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