Immune-related cardiovascular adverse events in a real-world cohort of patients treated with immune checkpoint inhibitors

In recent years, immunotherapy with immune checkpoint inhibitors (ICIs), including PD-1/PD-L1 and CTLA-4 inhibitors, has revolutionised the treatment of various malignancies. While these therapies have demonstrated significant efficacy, they also carry the risk of immune-related cardiovascular adverse events (irCVEs). Clinical manifestations of irCVEs range from asymptomatic alterations in cardiac biomarkers to severe conditions such as arrhythmias, myocarditis, pericarditis, left ventricular dysfunction, heart failure, and acute coronary syndrome. Although irCVEs are relatively rare, their true incidence in real-world settings remains poorly defined.

This initial real-world study included 102 patients undergoing cancer immunotherapy. The primary aim was to identify risk factors associated with irCVEs and determine potential correlations with immunotherapy.

Starting from July 2022 all patients underwent a comprehensive physical examination, electrocardiogram, echocardiogram, and measurement of high-sensitivity troponin I, NT-proBNP, and CPK levels at baseline and during treatment. Data were gathered from clinical evaluations, diagnostic tests, and medical records. A logistic regression analysis was performed to identify risk factors for irCVEs, excluding variables with an unbalanced distribution. Initially, a classical logistic regression model was applied using the Generalised Linear Model (GLM) in R, but no significant variables were found. Therefore, regularised GLM was used to improve prediction accuracy and prevent overfitting. The dataset was divided into a training group (70 patients) and a test group (32 patients). The model was optimised by tuning hyperparameters (penalty: 0.0000000001, mixture: 0) and validated based on performance metrics (accuracy: 94%, precision: 96%, sensitivity: 96%, specificity: 60%, F-measure: 0.94, Cohen’s Kappa: 0.61).

Observed irCVEs included 3 cases of myocarditis, 1 pericarditis, 3 heart failures, 1 atrial fibrillation, 2 acute coronary syndromes and mainly at first administration. Independent risk factors for irCVEs included obesity, dyslipidaemia, atrial fibrillation, and coronary artery disease. No patients died from irCVEs.

Immunotherapy remains a highly promising treatment option for cancer patients. However, early detection and risk stratification of irCVEs are crucial to mitigating their potentially severe consequences and improving oncological outcomes. This study provides valuable insights into the real-world impact of irCVEs; however, further research is required to refine predictive models and develop standardised prevention protocols. Results should be interpreted with caution due to the limited sample size and low frequency of irCVEs. Additionally, underrepresentation of certain variables may have biased the estimates. Ongoing efforts aim to increase the sample size in future studies.