Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor-Induced Myocarditis

BACKGROUND Myocarditis is a dreaded and unpredictable complication of immune checkpoint inhibitors (ICI). We sought to determine whether routinely measured biomarkers could be helpful in monitoring for ICI myocarditis.OBJECTIVES The authors examined biomarker trends of patients on ICI and their association with the incidence of ICI myocarditis and outcomes.METHODS We conducted an observational cohort study of adults who received at least one dose of ICI at Michigan Medicine between June 2014 and December 2021 and underwent systematic serial testing for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase during ICI therapy.RESULTS Among 2,606 patients (mean age 64 +/- 13 years; 60.7% men), 27 (1.0%) were diagnosed with ICI myocarditis. At diagnosis, patients with myocarditis had an elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and lactate dehydrogenase (92.6%). Findings were confirmed in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. A total of 95% of patients with ICI myocarditis had elevations in at least 3 biomarkers compared with 5% of patients without myocarditis. Among the noncardiac biomarkers, only CPK was associated (per 100% increase) with the development of myocarditis (HR: 1.83; 95% CI: 1.59-2.10) and all-cause mortality (HR: 1.10; 95% CI: 1.01-1.20) in multivariable analysis. Elevations in CPK had a sensitivity of 99% and specificity of 23% for identifying myocarditis.CONCLUSIONS ICI myocarditis is associated with changes in AST, ALT, and CPK. An increase in noncardiac biomarkers during ICI treatment, notably CPK, should prompt further evaluation for ICI myocarditis. (J Am Coll Cardiol CardioOnc 2022;4:689-700)(c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study aimed to determine the biomarker trends and their association with the incidence and outcomes of immune checkpoint inhibitor (ICI) myocarditis. The results showed that patients with ICI myocarditis had elevated levels of AST, ALT, and CPK. An increase in noncardiac biomarkers, especially CPK, during ICI treatment should prompt further evaluation for ICI myocarditis.