A two-stage ensemble learning based prediction and grading model for PD-1/PD-L1 inhibitor-related cardiac adverse events: A multicenter retrospective study

•The performance of existing prediction models for immune-related cardiac adverse reactions is relatively low, and there is no graded prediction model for these reactions.•This study presents a novel two-stage ensemble machine-learning strategy for predicting and grading immune-related cardiac adverse reactions. The proposed method demonstrates good performance.•The two-stage ensemble learning model for predicting and grading immune-related cardiac adverse reactions holds potential clinical application value in preventing and treating patients. Immune-related cardiac adverse events (ircAEs) caused by programmed cell death protein-1 (PD-1) and programmed death-ligand-1 (PD-L1) inhibitors can lead to fulminant and even fatal consequences. This study aims to develop a prediction and grading model for ircAEs, enabling graded management of patients. This study utilized medical record systems from two medical institutions to develop a prediction and grading model for ircAEs using ten machine learning algorithms and two variable screening methods. The model was developed based on a two-stage ensemble learning framework. In the first stage, the ircAEs and non-ircAEs cases were classified. In the second stage, ircAEs cases were grouped into grades 1–2 and 3–5. The experiments were evaluated using five-fold cross-validation. The model's prediction performance was assessed using accuracy, precision, recall, F1 value, Brier score, receiver operating characteristic curve area (AUC), and area under the precision-recall curve (AUPR). 615 patients were included in the study. 147 experienced ircAEs, and 44 experienced grade 3–5 ircAEs. The soft voting classifier trained using the variables screened by feature importance ranking performed better than other classifiers in both stages. The average AUC for the first and second stages is 84.18 % and 85.13 %, respectively. In the first stage, the three most important variables are N-terminal B-type natriuretic peptide (NT-proBNP), interleukin-2 (IL-2), and C-reactive protein (CRP). In the second stage, the patient's age, NT-proBNP, and left ventricular ejection fraction (LVEF) are the three most critical variables. The prediction and grading model of ircAEs based on two-stage ensemble learning established in this study has good performance and potential clinical application.