Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors

Our plain-English summary of Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors, by S. Petricciuolo, M.G. Delle Donne, A. Aimo, et al (European Journal of Clinical Investigation, 2021).

The study

• Authors: S. Petricciuolo, M.G. Delle Donne, A. Aimo, A. Chella, R. De Caterina
• Journal: European Journal of Clinical Investigation
• Published: 2021;51(4):e13400
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Immune checkpoint inhibitors (ICIs) are an emerging option for several advanced metastatic cancers, but may have cardiotoxic effects. The prognostic value of high-sensitivity troponin T (hs-TnT) before treatment start has never been investigated.

Materials And Methods: Thirty consecutive patients underwent measurement of hs-TnT before starting ICI therapy (pembrolizumab, 23%; nivolumab, 12%; atezolizumab, 6%; durvalumab, 5%). The primary endpoint of cardiovascular death, stroke or transient ischaemic attack, pulmonary embolism and new-onset heart failure, and the secondary endpoint of progression of cardiac involvement according to the CARDIOTOX classification were evaluated after 3 months from the first cycle.

Results: Patients (median age 68 years, 77% men, 13% with coronary artery disease, 90% current or former smokers, 67% overweight or obese and 43% hypertensive) had a median hs-TnT of 12 ng/L (interquartile interval 8-23). The primary endpoint occurred only in patients with hs-TnT ≥ 14 ng/L at baseline. Therefore, only patients who had hs-TnT ≥ 14 ng/L before the first cycle died had a stroke/TIA or new-onset HF. Furthermore, nine out of 13 patients with the secondary endpoint (progression of cardiac disease) had hs-TnT ≥ 14 ng/L before the first cycle (P = .012). AUC values were 0.909 for the primary endpoint and 0.757 for the secondary endpoint. The best cut-off was 14 ng/L for both the primary (100% sensitivity, 73% specificity) and secondary endpoints (sensitivity 75%, specificity 77%).

Conclusions: In patients on ICIs, baseline hs-TnT predicts a composite cardiovascular endpoint and the progression of cardiac involvement at 3 months, with 14 ng/L as the best cut-off.

© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

In plain English

This study, from Pisa University Hospital in Italy, followed 30 consecutive patients with advanced lung cancer or pleural mesothelioma who started immune checkpoint inhibitor cancer drugs between September 2019 and March 2020. Before the first dose, the authors measured high-sensitivity troponin T, a blood marker of heart muscle damage. The study did not look at asbestos exposure. At 3 months, 7 patients (23%) had the main combined outcome. Two died of cardiovascular causes, 2 had a stroke or transient ischemic attack, and 3 developed heart failure. All of these events occurred in patients whose starting troponin T was 14 ng/L or higher. Heart involvement worsened on the CARDIOTOX grading scale in 13 patients (43%), and 9 of those 13 had a starting level of 14 ng/L or higher. The authors concluded that baseline troponin T predicted these outcomes, with 14 ng/L as the best cut-off. They called the study preliminary and hypothesis-generating, citing its small size and short follow-up.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective cohort study of consecutive patients, with 3-month follow-up; the authors describe it as a preliminary, hypothesis-generating study
• Who was studied: 30 consecutive adults at the University Hospital of Pisa, Italy, starting immune checkpoint inhibitor therapy from September 2019 to March 2020. All had stage IIIb or IV squamous cell lung cancer, lung adenocarcinoma, neuroendocrine lung cancer or pleural mesothelioma. Table 1 lists 3 patients (10%) with pleural mesothelioma. Patients with left ventricular ejection fraction below 50% or clinical heart failure were excluded.
• Exposure: Immune checkpoint inhibitor drugs: pembrolizumab (200 mg every 21 days), nivolumab (240 mg every 15 days), durvalumab (10 mg/kg every 44 days) and atezolizumab (1200 mg every 21 days), all given intravenously. The predictor studied was high-sensitivity troponin T measured before the first cycle. No asbestos exposure was studied.
• Main results:
  • At 3 months, 7 of the 30 patients (23%) had experienced the primary composite endpoint: 2 cardiovascular deaths, 2 strokes or transient ischemic attacks, and 3 cases of new heart failure.
  • Of the 2 cardiovascular deaths, one was from myocardial infarction and one from pericardial tamponade.
  • The primary endpoint occurred only in patients whose baseline high-sensitivity troponin T was 14 ng/L or higher.
  • 13 patients (43%) showed progression of cardiac involvement on the CARDIOTOX classification over 3 months: 3 from normal to mild, 1 from normal to moderate, 5 from mild to moderate, and 4 from mild to severe.
  • Of the 13 patients with progression of cardiac involvement, 9 had baseline troponin T of 14 ng/L or higher (p=0.012).
  • Area under the curve for baseline troponin T was 0.909 for the primary endpoint, 0.796 for cardiovascular death alone, and 0.757 for the secondary endpoint.
  • The best cut-off was 14 ng/L for all three outcomes: primary endpoint (100% sensitivity, 73% specificity), cardiovascular death (100% sensitivity, 59% specificity), and secondary endpoint (75% sensitivity, 77% specificity).
  • Among baseline patient characteristics, estimated glomerular filtration rate (kidney function) was the only independent predictor of troponin T levels.
• The authors' conclusion: The authors concluded that, in patients treated with immune checkpoint inhibitors, baseline high-sensitivity troponin T predicts a composite cardiovascular endpoint and the progression of cardiac involvement over 3 months, with 14 ng/L as the best cut-off. They added that this should be verified in larger cohorts with longer follow-up.
• Limitations the authors state:
  • The small population and short follow-up gave few events. This required a heterogeneous combined primary endpoint and prevented multivariable analysis.
  • Different drugs and tumour types were analysed together, although cardiac risk could vary by drug, by primary tumour site (lungs versus pleural spaces) or by tumour type.
  • Only baseline troponin T was studied, not its changes during treatment cycles.
  • Baseline troponin I was not assessed.
  • Natriuretic peptides were not systematically measured.
  • Follow-up did not include cardiovascular magnetic resonance, which could have detected subclinical myocarditis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Pembrolizumab (Keytruda), Nivolumab (Opdivo), Atezolizumab (Tecentriq), Durvalumab (Imfinzi).

Related studies

• Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab — J.S. Lin, D.Y. Wang, et al. (2020)
• Immune checkpoint inhibitors a new player in the therapeutic game of mesothelioma: New reality with new challenges — K. Parikh, L.E.L. Hendriks, et al. (2021)
• Primary pericardial mesothelioma: a case report of a patient treated with an immune checkpoint inhibitor as the second-line treatment — O. Arponen, V. Salo, et al. (2021)
• Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations — N. Principe, W.J. Aston, et al. (2022)
• Immune Checkpoint Inhibition for Unresectable Malignant Pleural Mesothelioma — W. Cui, S. Popat (2021)
• Epigenetic Alterations and Biomarkers for Immune Checkpoint Inhibitors-Current Standards and Future Perspectives in Malignant Pleural Mesothelioma Treatment — Y. Yoshikawa, K. Kuribayashi, et al. (2020)

Browse return to medical research.