Immune checkpoint inhibitor-associated myocarditis: a review of current state of knowledge

Abstract

Background: Immune checkpoint inhibitors (ICIs) have changed the landscape in oncology, providing effective cancer management for a growing population. However, by promoting an immunological attack on cancer cells, healthy cells may be harmed in the process. Increased awareness of ICI-associated myocarditis (ICIMy) as one of the most fatal immune-related adverse events has led to efforts to improve the diagnosis and treatment of this condition. The purpose of this review is to summarize the current state of knowledge regarding ICIMy. Methods: We performed a literature search in Pubmed and Scopus with the relevant keywords, screened the titles and abstracts of the results, and reviewed the selected publications using pre-established criteria. Main findings: Although ICIMy’s cumulative incidence is below 0.5% in clinical trials, real-world data reveal a higher incidence of up to 4%. Underlying pathophysiologic mechanisms include T cell clonal expansion, molecular mimicry, and increased inflammatory cytokine signaling pathways leading to ICIMy. The clinical presentation can vary from asymptomatic to fulminant cardiac death and is often accompanied by musculoskeletal adverse events. Emerging diagnostic tools with prognostic value include global longitudinal strain assessment and multiple PET-CT modalities. The mainstay of treatment includes holding the immunotherapy, prompt high-dose methylprednisolone, and close cardiovascular observation. Fulminant and refractory cases benefit from additional immunomodulatory therapies. Principal conclusions: Although ICIMy is a rare adverse event, its non-specific presentation warrants a high level of suspicion. Once ICIMy is considered a likely diagnosis, immunomodulatory therapies should be initiated promptly.

Keywords

ICI-myocarditis / immune checkpoint inhibitors / immune-related adverse event / cardiotoxicity / autoimmunity

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