Serum Troponin T Concentrations Are Frequently Elevated in Advanced Skin Cancer Patients Prior to Immune Checkpoint Inhibitor Therapy: Experience From a Single Tertiary Referral Center

Abstract

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several human malignancies, particularly metastatic skin cancer. However, immune-related myocarditis (irM), an immune-mediated adverse event (irAE), is often fatal. In the absence of a reliable biomarker, measurement of pre-ICI therapy serum troponin concentration has been proposed to identify patients at risk of developing irM, although real-world studies examining this strategy are lacking. Thus, we retrospectively analyzed the case records of all patients who commenced ICI therapy between January 2018 and December 2019 in a single university skin cancer center (n = 121) to (i) determine the incidence of irM, (ii) establish the frequency of pretreatment serum hsTnT elevations, and (iii) to establish whether this identified patients who subsequently developed irM. Only one patient developed irM, resulting in an overall incidence of 0.8%. Pretreatment hsTnT was measured in 47 patients and was elevated in 13 (28%). Elevated serum hsTnT concentrations were associated with chronic renal failure (p = 0.02) and diabetes (p < 0.0002). Pretreatment hsTnT was not elevated in the patient who developed fulminant irM. Pre-immunotherapy serum hsTnT concentrations were often asymptomatically elevated in patients with advanced skin cancer, none of whom subsequently developed irM during ICI therapy. However, large studies are required to assess the positive and negative predictive values of hsTnT for the development of irM. In the meantime, elevated hsTnT concentrations should be investigated before initiation of immunotherapy and closely monitored during early treatment cycles, where the risk of irM is greatest.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study

“…Furthermore, pre-ICI TTEs were not investigated and TTEs during treatment were performed at different time points. Kurzhals et al retrospectively analyzed pre-treatment hs-TnT levels in 47 patients who subsequently received ICI therapy for locally advanced and/or metastatic melanoma [47]. One patient, who had normal pre-treatment hs-TnT, developed myocarditis.…”

Aberrant Expression of Cardiac Troponin-T in Lung Cancer Tissues in Association With Pathological Severity

“…Finke et al ( 32 ) recently reported that high levels of circulating cardiac troponin-T before starting chemotherapy predicted all-cause mortality after adjusting to glomerular filtration rate, age, gender, hypertension, diabetes, and adiposity, in which 86.7% (806 of 930) patients having a left ventricular ejection fraction > 50%. Prior cardiovascular disease, co-morbidity, hemodynamic instability, and pro-inflammatory cytokines produced from cancer cells damaged myocardial cells might affect the circulating cardiac troponin-T level ( 13 , 14 , 33 , 34 ). Assessment of troponin-T helps to identify patients with cardiotoxicity during cancer therapy ( 35 ), and preventative therapy with β-blocker and angiotensin converting enzyme inhibitor/angiotensin II receptor blocker were associated with less cardiac troponin-T elevation in cancer patients ( 36 ).…”

“…Although the circulating troponin-T levels in the peripheral blood were not evaluated at the time of tumor resection/biopsy, this study suggests a considerable attention may need to interpretate the cardiac troponin-T levels in the serum of cancer patients; circulating troponin-T from the tumor tissue may give false diagnosis of myocardial injury ( 16 ). However, it is noted that serum cardiac troponin-T level can be elevated with pre-existing/subclinical cardiac or noncardiac disorders without manifested cardiac dysfunction, meanwhile apparent normal cardiac function with elevated cardiac troponin-T cannot deny the presence of latent myocardial injury ( 34 , 37 ). We observed TNNT2 positive staining regardless of presence (+) or absence (-) of cardiovascular comorbidities (CVM): TNNT2(-)/ CVM(-), 13; TNNT2(-)/ CVM(+), 30; TNNT2( + )/ CVM(-), 14; TNNT2( + )/ CVM(+), 11 in 68 cancer patients.…”

Myocarditis Induced by Immunotherapy in Metastatic Melanoma—Review of Literature and Current Guidelines

“…Melanoma was reported to be the second most frequent cancer associated with cardiac metastases, after mesothelioma, so the progression of the disease and heart failure related to increasing after-load should be always taken into consideration [ 83 , 84 ]. Also, Kurzhals et al (2021) reported elevations of serum troponin T levels in 28% of patients with advanced skin cancer prior to the beginning of the therapy, and the pre-therapeutic elevated troponin T concentrations were not associated with the development of myocarditis [ 85 ]. However, if and how the extent to which metastatic melanoma per se is associated with increased serum troponin T concentrations needs to be confirmed in larger studies.…”