Researchers have identified noncardiac biomarkers that may predict myocarditis associated with immune checkpoint inhibitor (ICI) treatment.

An increase in these biomarkers during ICI treatment “should prompt further evaluation for ICI myocarditis,” the researchers wrote in JACC CardioOncology

The researchers conducted an observational study of 2606 adults who had received at least 1 dose of an ICI between June 2014 and December 2021. Patients had melanoma, lung cancer, gastrointestinal cancer, genitourinary cancer, and other malignancies.

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All patients underwent serial testing for aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK), and lactate dehydrogenase (LDH) during ICI treatment.

A total of 27 patients (1.0%) were diagnosed with ICI myocarditis. The median time from the first dose of an ICI to myocarditis was 28 days (range, 1-209), and 55.6% of patients developed myocarditis within 30 days. 

Patients diagnosed with myocarditis had elevated high-sensitivity troponin T (100%), ALT (88.9%), AST (85.2%), CPK (88.9%), and LDH (92.6%).

The researchers confirmed these findings in an independent cohort of 30 patients with biopsy-confirmed ICI myocarditis. In this group, elevations of ALT (100%), AST (96.7%), CPK (83.3%), and LDH (96.7%) were common at myocarditis diagnosis.

In both cohorts with ICI myocarditis (n=57), all patients had elevated levels of at least 1 noncardiac biomarker, and 95% had elevations in at least 3 of the biomarkers. Of the patients without myocarditis (n=2579), 5% had elevations in at least 3 of the biomarkers. 

In a multivariable analysis, only CPK was significantly associated with an increased risk of myocarditis (hazard ratio [HR], 1.83; 95% CI, 1.59-2.10; P =.007) and all-cause mortality (HR, 1.10; 95% CI, 1.01-1.20; P =.029). CPK had a sensitivity of 99% and a specificity of 23% for acute ICI myocarditis.

Based on these findings, the researchers concluded that patients who have elevated CPK, ALT, and AST during ICI treatment should have cardiac biomarkers measured. If the cardiac biomarkers are abnormal, this should “prompt clinicians to conduct a thorough evaluation for acute myocarditis or initiate more frequent cardiac monitoring while minimizing treatment disruptions,” the researchers wrote.


Vasbinder A, Chen Y, Procureur A, et al. Biomarker trends, incidence, and outcomes of immune checkpoint inhibitor-induced myocarditis. JACC CardioOncol. 2022;4(5):689-700.