Immune Checkpoint Inhibitor-Induced Myocarditis Is Associated With Changes in 3 Biomarkers

In a study published in JACC: CardioOncology, investigators found that nearly all patients with cancer who were diagnosed with myocarditis after being treated with immune checkpoint inhibitors (ICIs) had early signs of muscle destruction and liver damage.

"While immune checkpoint inhibitors have revolutionised the treatment of various cancers, patients who develop the rare complication of myocarditis often present late with at least a 50% chance of death," said Salim Hayek, MD, University of Michigan Health Frankel Cardiovascular Center Clinics, Ann Arbor, Michigan. "Diagnosing immune checkpoint inhibitor myocarditis is challenging, given that there is no one test that can differentiate it from other causes of cardiac injury. By the time patients present to the hospital, it is often too late. Diagnosing patients early allows us to start immunosuppressive therapy sooner and give patients a better chance of survival."

The researchers analysed more than 2,600 patients with cancer treated with ICIs at the University of Michigan Health between June 2014 and Dec. 2021. The vast majority of patients diagnosed with ICI-induced myocarditis also had early signs of muscle injury and liver damage, even prior to hospitalisation. Of the patients, 95% had at least 3 elevated biomarkers -- aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase (CPK) -- compared with just 5% of patients without myocarditis.

CPK was most strongly linked to the development of ICI-induced myocarditis, as well as all-cause death.

"Abnormalities in these biomarkers should prompt clinicians to test for cardiac injury using high sensitivity troponin," said Dr. Hayek. "Conversely, patients suspected of immune checkpoint myocarditis should have creatine phosphokinase levels measured. If low, or within normal limits, then the diagnosis of immune checkpoint myocarditis is highly unlikely."

"It makes sense that myocarditis related to immune checkpoint inhibitors does not occur in isolation, given a raging immune system is expected to affect several organs and particularly the muscles," said coauthor Joe-Elie Salem, MD, Sorbonne Université, Paris, France. "A large variety of antigens targeted by auto-reactive T-cells boosted by ICIs are shared between the myocardium and the peripheral muscles. Myositis is a central component of complications related to this class of drugs."

Reference:https://www.sciencedirect.com/science/article/pii/S2666087322004598

SOURCE: Michigan Medicine - University of Michigan

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