A real-world cohort study of immune-related adverse events in patients receiving immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) have significantly improved patient survival outcomes across various cancer types. However, their use is often associated with immune-related adverse events (irAEs), posing challenges in clinical management. Understanding the incidence, severity, and risk factors of irAEs is critical for optimizing ICI therapy and minimizing adverse outcomes. ObjectiveThis study aimed to identify and evaluate risk factors for immune-related adverse events (irAEs) among patients receiving ICIs, focusing on patient demographics, comorbidities, cancer types, and ICI regimens. Additionally, we sought to examine the incidence, severity, and organ-specific patterns of irAEs to guide personalized management strategies. MethodsThis retrospective cohort study utilized real-world data from the OneFlorida+ Clinical Research Network, including 9,193 adult patients who received ICIs between January 2018 and December 2022. Patients were categorized based on whether they developed irAEs within one year of initiating ICI therapy. Multivariable logistic regression was employed to identify risk factors for irAEs, adjusting for key covariates such as age, sex, cancer type, smoking status, and comorbidities. Kaplan-Meier survival analysis and cumulative incidence functions were applied to evaluate time to irAE event and overall incidence, stratified by irAE severity, cancer type, and ICI regimens. ResultsOf the 6,526 patients included in the final analysis, 56.2% developed irAEs within one year of ICI treatment, including 284 severe cases. Female and younger patients (ages 18-29) were at higher risk of developing irAEs, while comorbidities such as myocardial infarction, congestive heart failure, and renal disease significantly increased irAE risk. In contrast, dementia was associated with a reduced risk of irAEs. Patients treated with combined CTLA4+PD(L)1 inhibitors exhibited a 35% higher risk of irAEs compared to PD-1 inhibitors alone (OR: 1.35, 95% CI: 1.14-1.60, P < 0.001). Cancer type also influenced irAE risk, with breast cancer (OR: 2.36, 95% CI: 1.57-3.60, P < 0.001) and hematological cancer (OR: 2.61, 95% CI: 1.40-5.14, P = 0.004) associated with higher risk compared to melanoma, whereas brain cancer had a reduced risk (OR: 0.55, 95% CI: 0.32-0.92, P = 0.025). Survival analysis revealed that irAE severity significantly impacts both the timing of irAE onset (P = 0.038) and overall survival (P < 0.0001). While treatment regimens significantly influenced irAE-free survival in multi-site cancers (P = 0.02) and overall survival in kidney cancer (P = 0.0011), their effects were less pronounced in other cancer types.