Elevations of Cardiac Troponin in Patients Receiving Immune Checkpoint Inhibitors: Data From a Prospective Study

Abstract

Background: Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of cancer. However, immune-related adverse events are prevalent in patients receiving ICI therapy. A serious immune-related adverse event is ICI-myocarditis, which is complex to diagnose given that the significance of early symptoms and biomarker trajectories, such as high-sensitivity troponin T (hs-TnT) are unclear. Objectives: The purpose of the study was to evaluate kinetics of hs-TnT in cancer patients receiving ICI and to identify patients at risk of developing ICI-myocarditis. Methods: This prospective, observational, single-center study included 164 patients receiving ICI therapy. Patients’ history, demographics, and clinical characteristics, as well as survival statistics, were collected from electronic patient records and used to analyze associations between elevated hs-TnT (≥14 ng/L) and a significant rise in hs-TnT (100% rise from baseline, with an absolute value ≥2x upper limit of normal (ie, ≥28 ng/L) with ICI-myocarditis. Results: We included 164 patients with a mean follow-up time of 1.60 ± 0.91 years. Melanoma was the most common type of cancer in the patient population, and most patients received treatment with programmed cell death protein 1 (PD-1). Twenty-six patients (16%) exhibited significant hs-TnT elevations, while 8 patients (5%) developed ICI-myocarditis. In 18 of 26 (69%) patients, ICI-myocarditis could not be diagnosed with certainty, while 10 of 26 (38%) patients had no other signs of symptoms of cardiac damage. All 8 myocarditis cases were preceded by significantly higher hs-TnT elevations than asymptomatic patients. Despite a high ICI-myocarditis incidence in our study population, cardiac mortality remained low (4%). Conclusions: Significant hs-TnT elevations occur more often than previously reported, are often asymptomatic, and do not always lead to myocarditis diagnosis.