Immune Checkpoint Inhibitor Myocarditis and Myotoxicity

Immune checkpoint inhibitor (ICI)–associated myocarditis is uncommon but has been described as an important and potentially fatal complication of cancer treatment. Increasing evidence from a variety of data sources have reframed this complication as part of ICI-associated myotoxicity (ICI-M), a systemic cardiomuscular syndrome in which myocarditis, myositis, conduction disease, ventricular arrhythmias, dysphagia, pseudo-myasthenic oculobulbar signs, and respiratory muscle failure may coexist. Elevated troponin with ICI use is not synonymous with myocarditis but instead should trigger a structured evaluation that considers symptoms, ECG findings, troponin and creatine kinase concentrations, structural and functional assessments including left ventricular function, pathology when feasible, and exclusion of alternative causes including other cardiotoxic therapies. The severity of ICI-M is heterogeneous and can now be stratified using the presence of active thymoma, cardiomuscular symptoms, low QRS-voltage, left ventricular ejection fraction <50%, and magnitude of troponin elevation. Low-risk cases such as patients with abnormal cardiac biomarkers only may be monitored closely, whereas severe ICI-M requires monitored admission, early respiratory and swallowing assessment, ICI interruption, and rapid multidisciplinary immunosuppression. Corticosteroids are generally recommended; however, severe, progressive, or refractory disease increasingly supports pathophysiology-directed-based therapies, including abatacept and ruxolitinib. Abatacept inhibits CD80/CD86–CD28 co-stimulation and can be titrated to CD86 receptor occupancy of the monocytes. Ruxolitinib inhibits Janus kinase/signal transducer and activator of transcription cytokine signaling pathway and may complement abatacept bioactivity. Evidence is promising for these therapies but not definitive, pending prospective trials. Rechallenge is often avoided but could be reassessed in selected patients under strict surveillance.