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.

INTRODUCTION: Immune checkpoint inhibitor(ICI) induced cardiac immune related adverse events are challenging to study; Leveraging large data bases like TriNetX global health network may provide needed insights. METHODS: We performed a retrospective cohort study including patients diagnosed neoplasm and 18 and older when receiving ICI therapy from 1/1/2011 to 12/31/2022. Queried ICD 9/10 codes identified patients experiencing myocarditis, pericarditis, pericardial effusion, and cardiac tamponade within 1 year of ICI initiation. Survival analyses compared one-year overall survival (OS) of patients experiencing cardiac irAEs against propensity score matched populations not experiencing them. RESULTS: In 88,928 identified ICI patients, the incidence of myocarditis(0.48%), pericarditis(0.22%), and cardiac tamponade(0.47%) were less than 1% while pericardial effusion occurred in 4.71% of patients. Hazard ratios (HRs) were significantly higher in all cardiac irAE groups: myocarditis (HR:1.26, 95% CI:1.04-1.54, p = 0.02), pericarditis (HR:1.36, 95% CI:1.02-1.82, p = 0.04), pericardial effusion (HR:1.49, 95% CI:1.39-1.59, p < 0.0001), cardiac tamponade (HR:2.15, 95% CI:1.79-2.57, p < 0.0001), and overall pericardial disease (HR:1.46, 95% CI:1.37-1.56, p < 0.0001). There was no significant difference in OS between myocarditis and pericarditis or overall pericardial diseases. DISCUSSION/CONCLUSION: Utilizing a uniquely large cohort of ICI patients, this study further shows the rarity of cardiac inflammatory irAEs and highlights their significant impact on patient survival.