The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer; however, at the potential cost of serious adverse events including cardiac injury.

Objective: To assess the baseline and longitudinal changes in high sensitivity-Troponin (hs-Tn) in patients treated with pembrolizumab as a potential predictor for the development of major adverse cardiac events (MACE) and survival.

Methods: We performed a retrospective analysis of cancer patients treated with pembrolizumab at our center. All participants had baseline measurements of hs-TnI prior to initiation of pembrolizumab (T1), with half of the patients performing follow-up measurements at their second encounter for therapy introduction (T2). We first evaluated the prevalence of abnormally elevated serum hs-TnI (> 50 nanogram per liter) at T1 and T2. We then evaluated the predictive value of abnormal levels at T1 or T2 in relation to the development of MACE (composite outcomes of myocarditis, acute coronary syndrome, heart failure, venous thromboembolism, cardiovascular hospitalization and cardiovascular mortality) and all-cause mortality.

Results: Among 135 patients, the mean age was 72 years, predominantly male (61%). Abnormally elevated hs-TnI at T1 was observed in 7 (5%) patients and emerged as a significant independent predictor for MACE (HR 8.1, 95% CI 1.67-37.4, p = 0.009) and all-cause mortality (HR 5.37, 95% CI 2.1-13.57, p < 0.001). Abnormally elevated hs-TnI at T2 was observed in 8 (11%) patients and emerged as a significant independent predictor for MACE (HR 10.49, 95% CI 1.68-65.5, p = 0.009), but not for mortality (p = 0.200).

Conclusions: Abnormally elevated baseline and follow-up hs-TnI served as significant independent predictors for MACE, with an increased risk of development being 8-tenfold. Furthermore, elevated baseline hs-TnI showed a predictive value for all-cause mortality. Central illustration: Novel immune checkpoint inhibitor (ICIs) therapy has been found to revolutionize cancer therapy through increased activation of host immune systems to target and reduce tumor burden, but may come at the cost of serious adverse cardiac events. Identification of early biomarkers for the prediction and detection of these events is necessary.

Keywords: Cardio-oncology; Cardio-toxicity; High sensitivity; Immune checkpoint inhibitor; Troponin.