Refining the treatment of immune checkpoint inhibitor–associated myocarditis: Challenges, innovations and rechallenge considerations

Immune checkpoint inhibitor (ICI)-associated myocarditis has emerged as a severe and clinically complex immune-related toxicity that poses significant challenges for therapeutic decision-making in routine cardio-oncological care. High-dose corticosteroids remain the first-line therapy, yet their timing, dosage and tapering require careful clinical judgement. Early initiation substantially improves outcomes, but steroid resistance or delayed response is common and necessitates escalation to second- and third-line immunosuppression or rescue therapies. The heterogeneity of available rescue therapies, including mycophenolate mofetil, abatacept, JAK inhibitors, plasmapheresis and other targeted agents, creates significant uncertainty, because evidence is largely limited to case reports and small case series. Management of ICI-induced myocarditis requires balancing immunosuppression with cancer control, particularly when considering rechallenge. Prognostic uncertainty and limited long-term data necessitate multidisciplinary, risk-adapted care, while robust prospective evidence and standardised algorithms remain urgently needed. This review summarises current management strategies for ICI-induced myocarditis, encompassing early high-intensity corticosteroid therapy, treatment of fulminant disease, and the use of second- and third-line and rescue immunosuppressive agents. Key clinical challenges, including steroid resistance, preservation of antitumour efficacy, ICI rechallenge, and emerging biomarker-driven and translational approaches, are also addressed to support individualised care.