Role of Biomarkers in the Management of Immune-Checkpoint Inhibitor-Related Myocarditis

Abstract

Purpose of review: Immune checkpoint inhibitor (ICI)-related myocarditis poses a major clinical challenge given its non-specific presentation, rapid progression, and high mortality rate. Here, we review the role of blood-based biomarkers in the clinical management of patients with ICI-related myocarditis.

Recent findings: Myocardial injury, its unique pattern, and the co-occurrence with myositis are defining features of ICI-related myocarditis. Non-cardiac biomarkers, specifically creatinine phosphokinase, precedes the symptomatic presentation and is highly sensitive for diagnosing ICI-related myocarditis, making them useful screening biomarkers. Combined elevations in cardiac troponins and non-cardiac biomarkers improve the confidence of an ICI myocarditis diagnosis. High troponin and creatinine phosphokinase levels are strongly associated with severe outcomes. We propose biomarker-based algorithms for the monitoring and diagnosis of ICI-related myocarditis. Biomarkers, such as cardiac troponins and creatine phosphokinase, can be used in combination in the monitoring, diagnosis, and prognostication of patients with ICI-related myocarditis.

Keywords: BNP; CPK; ICI; Myositis; Troponin; irAE.

Figure 1:. Diagnostic approach for suspected ICI-related myocarditis.

In patient on ICI therapy presenting with signs and symptoms concerning for ICI-related myocarditis: 1) if first ICI infusion is 60 days or > with normal CPK levels and rapidly downtrending troponin, there is a very low likelihood of ICI-related myocarditis and other causes of myocardial injury need to be ruled out. 2) If ICI therapy was initiated within 60 days, and the patient has abnormal CPK levels with stably elevated or rising troponin, the patient has a high likelihood of ICI-related myocarditis. Immunosuppression should be strongly considered after exclusion of acute coronary syndrome. ACS: acute coronary syndrome; CPK: creatine phosphokinase; ICI: immune checkpoint-inhibitors; hsTn: high sensitivity troponin.

Figure 2:. Screening strategy for ICI-related myocarditis.

For patients to receive ICI therapy, measure CPK, AST, and ALT at baseline and bi-weekly for the first 12 weeks after ICI initiation. If the aforementioned biomarkers are increasing, measure hsTn. 1) If hsTn is normal, the diagnosis of ICI-related myocarditis unlikely, and the hsTn level should be rechecked in a week. 2) For asymptomatic patients with an abnormal hsTn, ICI-related myocarditis is possible. A cardiac workup should rule out secondary causes of myocardial injury and hsTn should be re-checked within 48 hours. Patients should be monitored closely for symptoms. If hsTn begins to rise or symptoms develop, immunosuppressive should be considered after excluding other causes of myocardial injury. 3) Symptomatic patients with elevated hsTn should be admitted for cardiac workup and consideration of immunosuppressive therapy after exclusion of ACS. ALT: alanine aminotransferase; AST: aspartate aminotransferase; CPK: creatine phosphokinase; ICI: immune checkpoint-inhibitors; hsTn: high sensitivity troponin.