The medication’s increased immune activity may cause damage to various organ systems, including myocarditis, which is the most severe complication.

A novel biomarker-based approach has been developed by researchers at Michigan Medicine to detect a rare and fatal side effect brought on by monoclonal antibodies used to treat various cancers.

In new research reported in JACC: CardioOncology, researchers found that almost all cancer patients who were given immune checkpoint inhibitors and then were diagnosed with myocarditis also had early signs of muscle damage and liver damage.

“While immune checkpoint inhibitors have revolutionized the treatment of various cancers, patients who develop the rare complication of myocarditis often present late with at least a 50% chance of death,” explains senior author Salim Hayek.

“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,” adds the author. “Diagnosing patients early allows us to start immunosuppressive therapy sooner and give patients a better chance of survival.”

Monoclonal antibodies known as immune checkpoint inhibitors, or ICIs, boost the body’s defenses against malignant cells. There is a chance that the medication’s heightened immune activity may turn against the body, harming practically any organ system; myocarditis being the most serious effect.

Researchers at the University of Michigan Health looked at more than 2,600 cancer patients who were given immune checkpoint inhibitors between June 2014 and December 2021. Even before they went to the hospital, the vast majority of people with ICI myocarditis already had signs of muscle damage and liver damage. Compared to merely 5% of individuals who did not have myocarditis, 95% of these patients exhibited at least three elevated biomarkers.

Creatine phosphokinase, a non-cardiac biomarker that indicates muscle damage, was most closely associated with both the emergence of ICI myocarditis and all-cause mortality.

“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,” points out co-author Joe-Elie Salem. “A large variety of antigens targeted by auto-reactive T-cells boosted by ICIs are shared between the myocardium and the peripheral muscles. Myositis, or muscle injury, is a central component of complications related to this class of drugs.”

Researchers came to the conclusion that doctors should regularly check ICI patients for biomarkers of damage in other parts of the body, such as creatine phosphokinase for muscle damage, aspartate and alanine aminotransferase for liver damage, and lactate dehydrogenase for tissue damage.

“Abnormalities in these biomarkers should prompt clinicians to test for cardiac injury using high sensitivity troponin,” Hayek adds. “Conversely, patient 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.”

Source: 10.1016/j.jaccao.2022.11.004

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