Cardiovascular Toxicity Across the Cancer Immunotherapy Spectrum: Mechanisms and Management in Immune Checkpoint Inhibitor (ICI) and Chimeric Antigen Receptor T-Cell (CAR-T) Therapy.

purpose of reviewThis review evaluates the evolving landscape of cardiovascular toxicities associated with two pillars of modern cancer treatment: immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy. It examines their distinct immune-mediated pathophysiologies, clinical manifestations, and management frameworks. RECENT

findingsWhile ICIs carry a clinical trial incidence for cardiotoxicity of approximately 1%, real-world data suggest rates of 3-5%, with myocarditis sometimes manifesting early as part of a high-mortality "Triple M" or overlap syndrome. Major adverse cardiovascular events (MACE) occur in nearly 50% of ICI-myocarditis cases. Diagnosis relies on clinical presentation, biomarkers and cardiac magnetic resonance imaging (CMR) using the modified Lake Louise criteria, with late gadolinium enhancement (LGE) detection sensitivity increasing from 21.6% to 72.0% when imaged after four days of symptoms. Conversely, CAR-T cardiotoxicity is predominantly driven by cytokine release syndrome (CRS), which affects 49-93% of patients with currently licensed products. Severe CRS more than doubles the risk of cardiovascular events, including a 6-10% incidence of LVEF decline and a 4-18% incidence of arrhythmias. Recent advancements include machine learning models to predict MACE and structured screening programs to risk-stratify candidates. Cardiotoxicity remains a significant complication, highlighting the need for vigilant monitoring and early intervention. Management relies on baseline risk assessment and rapid deployment of targeted therapies, such as high-dose methylprednisolone for ICI-myocarditis and IL-6 inhibition (tocilizumab) for CAR-T-related CRS. A multidisciplinary cardio-oncology approach is essential to mitigate risks. With early diagnosis and appropriate immunosuppressive strategies in a multidisciplinary setting, these complications can be better managed, optimising oncological benefits whilst reducing treatment-related morbidity and mortality in majority of patients.