Immune Checkpoint Inhibitor-Associated Myocarditis: Risk, Diagnosis, and Clinical Impact
Alfredo Mauriello, Adriana Correra, Anna Chiara Maratea, Valeria Cetoretta, Giovanni Benfari, Federica Ilardi, Rosangela Cocchia, Matteo Lisi, Alessandro Malagoli, Giulia Elena Mandoli, Maria Concetta Pastore, Simona Sperlongano, Vincenzo Russo, M Cameli, Antonello D’Andrea
Abstract
Background: Immune checkpoint inhibitors (ICIs), such as anti-programmed death (PD)-1 and anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 agents, have revolutionized oncology but are associated with immune-related adverse events (irAEs). Among these, ICI-associated myocarditis (ICI-M) is a rare but life-threatening complication, with mortality rates ranging from 27% to 50%. Objective: This narrative review summarizes the pathogenesis, epidemiology, clinical presentation, diagnostic methods, and management strategies for ICI-induced myocarditis, specifically highlighting emerging biomarkers and immunosuppressive therapeutic approaches. Results and Discussion: ICI-M typically presents within the first 65 days of treatment and is significantly more frequent with combination therapies. Pathologically, it is characterized by myocyte necrosis and massive infiltration of cluster of differentiation (CD)4+ and CD8+ T-cells, often overlapping with myositis (irM/M). Diagnosis relies on a multimodal approach. Management requires immediate ICI cessation and initiation of high-dose corticosteroids as first-line therapy. For steroid-refractory cases, second-line options include mycophenolate mofetil (MMF), intravenous immunoglobulin (IVIG), and emerging therapies like abatacept and ruxolitinib. Rechallenge with ICIs after high-grade ICI-M must be approached with extreme caution by the multidisciplinary team (MDT). Emerging biomarkers and omics techniques hold promise for earlier diagnosis and risk stratification. Conclusions: ICI-M is a rare yet highly lethal cardiac complication demanding high clinical vigilance and timely diagnosis. Management hinges on an aggressive multidisciplinary approach, aiming to minimize toxicity while balancing oncological efficacy.