Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;26(12):1052-1061.
doi: 10.1002/onco.13931. Epub 2021 Aug 25.

Immune Checkpoint Inhibitor-Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

Ranjan Pathak  1 , Anjan Katel  2 , Erminia Massarelli  1 , Victoria M Villaflor  1 , Virginia Sun  3 , Ravi Salgia  1
Affiliations

Immune Checkpoint Inhibitor-Induced Myocarditis with Myositis/Myasthenia Gravis Overlap Syndrome: A Systematic Review of Cases

Ranjan Pathak et al. Oncologist. 2021 Dec.

Abstract

Background: The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immune-related adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature.

Materials and methods: Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.

Results: A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICIs (38%). The most-reported symptoms were fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9,645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. Sixty percent of the patients died in hospital because of acute complications.

Conclusion: IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition.

Implications for practice: Clinicians should suspect coexisting myositis and/or myasthenia gravis in all patients with immune checkpoint inhibitor-induced myocarditis, given their propensity to occur together. Early recognition and prompt treatment with the help of a multidisciplinary team might help improve the outcomes of this life-threatening condition.

Keywords: Immune checkpoint inhibitor; Immune checkpoint inhibitors; Immune-related adverse events; Induced myocarditis; Myasthenia gravis; Myocarditis; Myositis; Overlap syndrome.

PubMed Disclaimer

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1
Figure 1
Flow diagram describing the systematic search and study selection process.Abbreviation: ICI, immune checkpoint inhibitor.
See this image and copyright information in PMC

References

    1. Kostine M, Rouxel L, Barnetche T et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer—clinical aspects and relationship with tumour response: A single‐centre prospective cohort study. Ann Rheum Dis 2018;77:393–398. - PubMed
    1. Moslehi JJ, Salem JE, Sosman JA et al. Increased reporting of fatal immune checkpoint inhibitor‐associated myocarditis. Lancet 2018;391:933. - PMC - PubMed
    1. Zorzela L, Loke YK, Ioannidis JP et al. PRISMA harms checklist: Improving harms reporting in systematic reviews. BMJ 2016;352:i157. - PubMed
    1. Arora P, Talamo L, Dillon P et al. Severe combined cardiac and neuromuscular toxicity from immune checkpoint blockade: An institutional case series. Cardiooncology 2020;6:21. - PMC - PubMed
    1. Swali R. Pembrolizumab‐induced myositis in the setting of metastatic melanoma: An increasingly common phenomenon. J Clin Aesthetic Dermatol 2020;13:44–45. - PMC - PubMed

Publication types

Substances