Time dependent predictors of cardiac inflammatory adverse events in cancer patients receiving immune checkpoint inhibitors

Background: Cardio-inflammatory immune related adverse events (irAEs) while receiving immune checkpoint inhibitor (ICI) therapy are particularly consequential due to their associations with poorer treatment outcomes. Evaluation of predictive factors of these serious irAEs with a time dependent approach allows better understanding of patients most at risk.
Objective: To identify different elements of patient data that are significant predictors of early and late-onset or delayed cardio-inflammatory irAEs through various predictive modeling strategies.
Methods: A cohort of patients receiving ICI therapy from January 1, 2010 to May 1, 2022 was identified from TriNetX meeting inclusion/exclusion criteria. Patient data collected included occurrence of early and later cardio-inflammatory irAEs, patient survival time, patient demographic information, ICI therapies, comorbidities, and medication histories. Predictive and statistical modeling approaches identified unique risk factors for early and later developing cardio-inflammatory irAEs.
Results: A cohort of 66,068 patients on ICI therapy were identified in the TriNetX platform; 193 (0.30%) experienced early cardio-inflammatory irAEs and 175 (0.26%) experienced later cardio-inflammatory irAEs. Significant predictors for early irAEs included: anti-PD-1 therapy at index, combination ICI therapy at index, and history of peripheral vascular disease. Significant predictors for later irAEs included: a history of myocarditis and/or pericarditis, cerebrovascular disease, and history of non-steroidal anti-inflammatory medication use.
Conclusions: Cardio-inflammatory irAEs can be divided into clinically meaningful categories of early and late based on time since initiation of ICI therapy. Considering distinct risk factors for early-onset and late-onset events may allow for more effective patient monitoring and risk assessment.