Immune checkpoint inhibitors and cardiovascular toxicity: immunology, pathophysiology, diagnosis, and management

Abstract

Immune checkpoint inhibitors (ICIs) are pivotal in cancer therapy, particularly but not solely for metastatic and advanced lung cancer. These monoclonal antibodies, targeting programmed cell death (PD)-1, ligand PD-L1, and cytotoxic T-lymphocyte antigen (CTLA)-4, enhance immune responses against tumors but can also trigger immune-related adverse events, including cardiotoxicity and vascular toxicity. Cardiotoxic effects, such as myocarditis, pericarditis, atrial arrhythmias, thrombosis, and vasculitis are significant concerns, particularly myocarditis that can be fatal. ICIs like pembrolizumab, nivolumab, and atezolizumab are widely used, with combination immunotherapy showing improved survival but higher myocarditis risk. Effective management of ICI-induced cardiovascular toxicity involves regular monitoring for physical findings, cardiac, inflammatory, and autoimmune biomarkers, electrocardiograms, CT angiograms, echocardiograms, and cardiac MRI as needed. Emergent treatment for ICI myocarditis and vasculitis includes immediate discontinuation of ICIs, high-dose corticosteroids, and supportive care. In severe or steroid-refractory cases, additional immunosuppressive therapies should be considered.