Researchers devised a new biomarker strategy to identify patients treated with immune checkpoint inhibitors (ICIs) who may develop myocarditis.Some biomarkers were raised up to 30 days before admission for myocarditis and could be useful as an early warning system, allowing immunosuppressive therapy to be initiated rapidly.
Although ICIs have revolutionized the treatment of various malignancies, the immune-related adverse dvent (irAE) events associated with them remain a problem. Myocarditis is the most severe cardiovascular manifestation of irAEs, with an estimated incidence of up to 2%.
In a paper published in JACC: CardioOncology, researchers present a panel of regularly measured 4 noncardiac biomarkers that can predict the onset of myocarditis up to 30 days before hospitalization.
The observational study included 2,606 adults treated with at least 1 dose of ICI between June 2014 and December 2021 and subjected to systematic serial analyses of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) during ICI therapy.
The data indicate that the vast majority of patients diagnosed with ICI myocarditis also had early signs of muscle injury and liver damage, even before hospitalization.95% of these patients had elevated levels of at least 3 biomarkers, compared with only 5% of patients without myocarditis.
The majority of patients with myocarditis had evidence of noncardiac irAE (88.9%) including hepatitis, myositis or elevated levels of AST, ALT and CPK. All ICI myocarditis patients had abnormal levels of high-sensitivity troponin T (hsTnT), suggesting that low levels of hsTnT could exclude the presence of ICI myocarditis. Most patients also had elevated levels of ALT (88.9%), AST (85.2%), CPK (88.9%), and LDH (92.6%) at the time of myocarditis diagnosis. The absence of elevated levels of ALT, AST, CPK and LDH could therefore help doctors rule out the presence of myocarditis. The researchers determined that CPK elevation alone has 99% sensitivity and 23% specificity of acute myocarditis diagnosis from ICI.
According to the authors, the high sensitivity of these markers and the fact that they are already measured regularly make them ideal screening tools for ICI myocarditis.
«Although immune checkpoint inhibitors have revolutionized the treatment of various cancers, patients who develop the rare myocarditis complication often present late, with a probability of death of at least 50%,» says Salim Hayek, senior author of the study.
«Diagnosis of myocarditis by immune checkpoint inhibitors is difficult, as there is no test that can differentiate it from other causes of heart injury.By the time patients arrive at the hospital, it is often too late. Early diagnosis of patients allows immunosuppressive therapy to be started earlier and therefore gives patients a better chance of survival.»
«Any abnormalities of these biomarkers should prompt physicians to evaluate for cardiac lesions using high-sensitivity troponin,» says Hayek. «Conversely, patients with suspected immune checkpoint myocarditis should be measured for creatine phosphokinase levels. If it is low or within normal limits, the diagnosis of myocarditis from immune checkpoint inhibitors is highly unlikely.»
According to the authors, evidence of elevated levels of ALT, AST and CPK should suggest the need to measure cardiac biomarkers; If results are abnormal, physicians should conduct a thorough evaluation of acute myocarditis or initiate more frequent cardiac monitoring to minimize treatment interruptions.
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Source — https://www.univadis.it/viewarticle/alcuni-biomarcatori-non-cardiaci-sono-predittivi-di-miocardite-da-inibitori-del-checkpoint-immunitario