Evaluating patients on immune checkpoint inhibitors for cardiac adverse events: The EPICC study

Abstract

Introduction

Immune checkpoint inhibitors (CPIs) work by engaging the patient's immune system against tumor cells and have demonstrated a significant benefit in the treatment of cancers. Activation of the patient's immune system can lead to immune-related adverse events (irAEs), which can affect almost any organ system, including the cardiovascular system. Although irAEs of the cardiovascular system are rare, they (and especially myocarditis) can be associated with high morbidity and mortality. With increased utilization of CPIs, it is paramount to evaluate the incidence and risk factors of cardiotoxicity from CPIs in a real-world practice.

Methodology

This is a retrospective cohort study conducted at a rural health system. Patients who were 18 years and older and received at least one dose of CPI from October 2013 through September 2021 were identified in electronic health records. Chart review was performed for patients who had at least one abnormal troponin level and were admitted to an acute care facility from the CPI start date through 30 days after CPI discontinuation. Exploratory associations between various characteristics and CPI-induced myocarditis were assessed with Fisher exact tests. Management and outcomes of patients with suspected CPI-induced myocarditis were captured from medical chart reviews.

Results

A total of 1515 patients were given at least one dose of a CPI between October 2013 and September 2021. Of those 1515 patients, 141 patients (9.3%) had an elevated troponin value while receiving CPI therapy or within 30 days after the last dose. Four patients with on-therapy elevated troponin were found to have myocarditis, making the incidence of suspected CPI-related myocarditis in this cohort 0.26% (95% CI: 0.07–0.67%). These case patients were more likely to have a history of acute myocardial infarction (MI), ST-elevation myocardial infarction (STEMI), or non-ST-elevation myocardial infarction (NSTEMI) (P = 0.01) as compared to included patients with no suspected myocarditis.

Conclusion

Our study confirms the findings of previous studies, that CPI-related myocarditis is a rare adverse event; however, more research is needed to determine risk factors.