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

Alexi Vasbinder, Yee Ann Chen, Adrien Procureur, Allison Gradone, Tariq U. Azam, Daniel Perry, Husam Shadid, Elizabeth Anderson, Tonimarie Catalan, Pennelope Blakely, Namratha Nelapudi, Mohamad Fardous, Marie C. Bretagne, Sarah K. Adie, Kristen T. Pogue, Monika Leja, Sarah Yentz, Bryan Schneider, Leslie A. Fecher, Christopher D. LaoJoe Elie Salem, Salim S. Hayek

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)689-700
Number of pages12
JournalJACC: CardioOncology
Volume4
Issue number5
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • ALT
  • AST
  • biomarkers
  • CPK
  • immune checkpoint inhibitor
  • immunotherapy
  • myocarditis
  • troponin

ASJC Scopus subject areas

  • Oncology
  • Cardiology and Cardiovascular Medicine

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