Myocarditis in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: A multicenter study.

Abstract

e20626 Background: Immune checkpoint inhibitors (ICIs) have improved survival in patients with lung cancer; however, their association with immune-related adverse events remains a significant challenge. While rare, ICI-related myocarditis can pose high mortality risk. There is a lack of comprehensive real-world data in the literature on ICI-related myocarditis. Methods: A retrospective cohort study was conducted using TriNetX, a combined claims and electronic health record database of more than 100 healthcare organizations. Patients with non-small cell lung cancer (NSCLC) treated with ICIs were compared to a 1:1 propensity score-matched cohort of patients treated with chemotherapy or targeted therapies. Primary outcomes included attributable risk of myocarditis, mortality, and ICU level care. ICI-associated myocarditis was defined as acute myocarditis occurring within 12 months of initiating ICI therapy. Within the ICI cohort, patients who developed myocarditis were compared to patients who did not develop myocarditis for the presence of major adverse cardiovascular events (MACE), as defined by myocardial infarction (MI), heart failure (HF), or stroke. Results: A total 44,263 non-small cell lung cancer patients who underwent ICI therapy were identified of whom 64 developed ICI-myocarditis. After propensity score matching, the risk of myocarditis attributable to immune checkpoint inhibitors (ICIs) compared to control group treated with chemotherapy/targeted therapies was 0.116% (95% CI, 0.076% to 0.156%) in the first year of therapy. ICI group had no increased risk of requiring critical care services (RR 1.027 (95% CI, 0.991 to 1.065) and had decreased mortality risk at one year (HR 0.909 [95% CI, 0.887 to 0.932]) and five years (0.969 [95% CI, 0.950 to 0.988]), compared to the control group. Within the ICI group, patients that developed myocarditis had a significantly higher risk of major adverse cardiovascular events (MACE) at one year compared to ICI patients that did not develop myocarditis (RR 3.740 [95% CI, 3.167 to 4.417]). Specific cardiovascular events also demonstrated significantly higher risks in the ICI myocarditis group including MI (RR 6.649 [95% CI, 4.672 to 9.464]), HF (RR 4.445 [95% CI, 3.526 to 5.603]), and stroke (RR 3.197 [95% CI, 1.807 to 5.658]). Conclusions: This large multicenter retrospective cohort study of patients with NSCLC from across the USA demonstrates that the risk of myocarditis is marginally higher compared to patients receiving chemotherapy or targeted therapies. Patients who developed ICI-associated myocarditis had a substantially higher risk of MACE, including myocardial infarction, heart failure, and stroke, compared to those receiving ICIs without myocarditis. These findings emphasize the need for careful monitoring of cardiovascular health in patients receiving ICIs.