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Therapeutic Agents for Steroid-refractory Immune Checkpoint Inhibitor-related Myocarditis: a Narrative Review

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Abstract

Background And Objective: Immune checkpoint inhibitors (ICIs) have become one of the cornerstones of current oncology treatment, and immune checkpoint inhibitor-related myocarditis (IRM) is the most fatal of all immune checkpoint inhibitor-related adverse events (irAEs). Methylprednisolone pulse therapy (500-1,000 mg/day) is the initial treatment for IRM recommended by almost all relevant guidelines. However, subsequent treatment regimens remain unclear for patients who do not respond to methylprednisolone pulse therapy (who are defined as steroid-refractory patients). We propose a potential treatment approach for steroid-refractory IRM.

Methods: The PubMed and the Cochrane Library databases were searched using keywords related to IRM. Relevant English-language articles published from January 2000 to February 2024 were included in this narrative review.

Key Content And Findings: Abatacept is the preferred choice for the treatment of isolated steroid-refractory IRM. For rapidly progressive or interleukin-6 abnormally elevated steroid-refractory IRM, alemtuzumab or tocilizumab/tofacitinib are the preferred therapeutic agents, respectively. For steroid-refractory IRM comorbid with myositis or comorbid with myasthenia gravis, abatacept + ruxolitinib/mycophenolate mofetil (MMF)/intravenous immunoglobulin (IVIG), or MMF + pyridostigmine/IVIG are the preferred therapeutic agents, respectively.

Conclusions: The pathogenesis of steroid-refractory IRM and the treatment regimen remain unclear. A large number of studies need to be conducted to validate or update our proposed treatment approach.

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