Abstract:
Objective To establish a predictive model for immune-related adverse events (irAEs) based on clinical and hematological markers in patients with malignancies treated with immune checkpoint inhibitors (ICIs). If validated, these markers have the advantage of being easily integrated into clinical practice with minimal costs.
Methods This was a retrospective study of patients with malignant tumors treated with at least one dose of ICIs at Tianjin Medical University Cancer Institute & Hospital and Shanxi Bethune Hospital from January 2016 to December 2020. Data on baseline characteristics, treatment details, and adverse events were collected. Student’s t-test, chi-square test, and Logistic regression were used to identify risk factors for irAEs to establish a prediction model.
Results The incidence rates of any grade and grade 3 or higher irAEs were 16.03% (76/474) and 2.32% (11/474), respectively. Endocrinopathy disorders (39/105, 37.1%) and pneumonitis (8/105, 7.6%) were the most commonly observed irAEs in the respective categories. Multivariate Logistic regression analysis showed that the risk of irAEs was higher in patients undergoing second-line treatment odds ratio (OR) = 3.302; globulin level (OR = 1.086) was positively correlated with the occurrence of irAEs, whereas direct bilirubin level (DBIL) (OR = 0.723) showed a negative correlation (P < 0.05). A prediction model based on “ICI type, line of treatment, globulin level, DBIL level, and lymphocyte to monocyte ratio (LMR)” was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) was 0.775 (95% CI: 0.711~0.840) with a cut-off value of 0.118, and the sensitivity and specificity were 92.5% and 56.6%, respectively.
Conclusions The prediction model based on “ICI type, line of treatment, globulin level, DBIL level, and LMR” demonstrated good predictive performance for irAEs in patients receiving ICIs alone, wherein the line of treatment, globulin level, and DBIL level were independent predictors for the onset of irAEs. Patients undergoing second-line ICIs therapy and exhibiting high globulin levels and low DBIL levels at baseline have a higher risk of irAEs.