Myotoxicity in the era of cancer immunotherapy: from mechanisms to multidisciplinary management

Myotoxicity, defined as immune-mediated injury to cardiac and/or skeletal muscle, has emerged as one of the most severe and lethal immune-related adverse events (irAE) in patients receiving immune checkpoint inhibitors (ICIs). Although myocarditis in oncology is not restricted to ICIs and may also occur after traditional cytotoxic chemotherapy, radiotherapy, or selected targeted therapies, ICI-associated cardiomyotoxicity is distinguished by its early onset, frequent overlap with myositis, and myasthenia gravis, and high case-fatality rate. This review outlines myotoxicity within the broader context of cancer therapy-related cardiovascular toxicity, then focuses on the distinct syndromes associated with different immunotherapy classes. For ICIs, we detail a spectrum including myocarditis, myositis, and overlap syndromes, quantified by data from large registries. For Chimeric Antigen Receptor (CAR) T-cell therapy, we focus on cardiotoxicity in the context of cytokine release syndrome (CRS). Diagnostic sections discuss clinical presentation, biomarkers, and imaging, emphasizing the need for troponin I over T and the nuanced interpretation of cardiac magnetic resonance (CMR). The POWER risk score is presented as the first externally validated tool to predict early major adverse cardiomyotoxic events (MACE) from ICIs. Finally, the review proposes distinct management strategies for ICI- versus CAR-T-related toxicity and outlines pragmatic surveillance protocols.