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Erschienen in: Clinical Research in Cardiology 3/2023

27.10.2022 | Original Paper

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

verfasst von: Barliz Waissengein, Bian Abu Ata, Ofer Merimsky, Sivan Shamai, Ido Wolf, Joshua H. Arnold, Tali Bar-On, Shmuel Banai, Shafik Khoury, Michal Laufer-Perl

Erschienen in: Clinical Research in Cardiology | Ausgabe 3/2023

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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.

Graphical abstract

Literatur
2.
Zurück zum Zitat Provencio M, Nadal E, Insa A et al (2020) Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol 21(11):1413–1422CrossRefPubMed Provencio M, Nadal E, Insa A et al (2020) Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol 21(11):1413–1422CrossRefPubMed
3.
Zurück zum Zitat Cascone T, William WN Jr, Weissferdt A et al (2021) Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med 27(3):504–514CrossRefPubMedPubMedCentral Cascone T, William WN Jr, Weissferdt A et al (2021) Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med 27(3):504–514CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Felip E, Altorki N, Zhou C et al (2021) Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial [published correction appears in Lancet. Lancet 398(10308):1344–1357 Felip E, Altorki N, Zhou C et al (2021) Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial [published correction appears in Lancet. Lancet 398(10308):1344–1357
6.
Zurück zum Zitat Emens LA, Ascierto PA, Darcy PK et al (2017) Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer 81:116–129CrossRefPubMed Emens LA, Ascierto PA, Darcy PK et al (2017) Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer 81:116–129CrossRefPubMed
7.
Zurück zum Zitat Guo CW, Alexander M, Dib Y et al (2020) A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies. Eur J Cancer 124:15–24CrossRefPubMed Guo CW, Alexander M, Dib Y et al (2020) A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies. Eur J Cancer 124:15–24CrossRefPubMed
8.
Zurück zum Zitat Lyon AR, Yousaf N, Battisti NML, Moslehi J, Larkin J (2018) Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol 19(9):e447–e458CrossRefPubMed Lyon AR, Yousaf N, Battisti NML, Moslehi J, Larkin J (2018) Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol 19(9):e447–e458CrossRefPubMed
9.
10.
Zurück zum Zitat Ball S, Ghosh RK, Wongsaengsak S et al (2019) Cardiovascular toxicities of immune checkpoint inhibitors: JACC review topic of the week [published correction appears in J Am Coll Cardiol. 2019 Nov 26;74(21):2711–2712]. J Am Coll Cardiol 74(13):1714–1727 Ball S, Ghosh RK, Wongsaengsak S et al (2019) Cardiovascular toxicities of immune checkpoint inhibitors: JACC review topic of the week [published correction appears in J Am Coll Cardiol. 2019 Nov 26;74(21):2711–2712]. J Am Coll Cardiol 74(13):1714–1727
11.
Zurück zum Zitat Liu S, Chan J, Brinc D et al (2020) Immune checkpoint inhibitor-associated myocarditis with persistent troponin elevation despite abatacept and prolonged immunosuppression. JACC CardioOncol 2(5):800–804 (Published 2020 Dec 15)CrossRefPubMedPubMedCentral Liu S, Chan J, Brinc D et al (2020) Immune checkpoint inhibitor-associated myocarditis with persistent troponin elevation despite abatacept and prolonged immunosuppression. JACC CardioOncol 2(5):800–804 (Published 2020 Dec 15)CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB (2018) Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 391(10124):933CrossRefPubMedPubMedCentral Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB (2018) Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 391(10124):933CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat van der Linden N, Klinkenberg LJJ, Bekers O et al (2016) Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population: a meta-analysis. Medicine (Baltimore) 95(52):e5703CrossRefPubMed van der Linden N, Klinkenberg LJJ, Bekers O et al (2016) Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population: a meta-analysis. Medicine (Baltimore) 95(52):e5703CrossRefPubMed
14.
Zurück zum Zitat Cardinale D, Sandri MT (2010) Role of biomarkers in chemotherapy-induced cardiotoxicity. Prog Cardiovasc Dis 53(2):121–129CrossRefPubMed Cardinale D, Sandri MT (2010) Role of biomarkers in chemotherapy-induced cardiotoxicity. Prog Cardiovasc Dis 53(2):121–129CrossRefPubMed
15.
Zurück zum Zitat Cardinale D, Sandri MT, Martinoni A et al (2000) Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 36(2):517–522CrossRefPubMed Cardinale D, Sandri MT, Martinoni A et al (2000) Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 36(2):517–522CrossRefPubMed
16.
Zurück zum Zitat Lyon A, Lopez-Fernandez T, Couch L et al (2022) 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J 00:1–133 Lyon A, Lopez-Fernandez T, Couch L et al (2022) 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J 00:1–133
17.
Zurück zum Zitat Lyon A, Dent S, Stanway S et al (2020) Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail 22(11):1945–1960CrossRefPubMed Lyon A, Dent S, Stanway S et al (2020) Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail 22(11):1945–1960CrossRefPubMed
18.
Zurück zum Zitat Mahmood SS, Fradley MG, Cohen JV et al (2018) Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 71(16):1755–1764CrossRefPubMedPubMedCentral Mahmood SS, Fradley MG, Cohen JV et al (2018) Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 71(16):1755–1764CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Visseren FLJ, Mach F, Smulders YM et al (2021) 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 42(34):3227–3337CrossRefPubMed Visseren FLJ, Mach F, Smulders YM et al (2021) 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 42(34):3227–3337CrossRefPubMed
20.
Zurück zum Zitat Lang RM, Bierig M, Devereux RB et al (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7(2):79–108CrossRefPubMed Lang RM, Bierig M, Devereux RB et al (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7(2):79–108CrossRefPubMed
21.
Zurück zum Zitat Lehmann LH, Cautela J, Palaskas N et al (2021) Clinical strategy for the diagnosis and treatment of immune checkpoint inhibitor-associated myocarditis: a narrative review. JAMA Cardiol 6(11):1329–1337CrossRefPubMed Lehmann LH, Cautela J, Palaskas N et al (2021) Clinical strategy for the diagnosis and treatment of immune checkpoint inhibitor-associated myocarditis: a narrative review. JAMA Cardiol 6(11):1329–1337CrossRefPubMed
22.
Zurück zum Zitat Gandhi L, Rodríguez-Abreu D, Gadgeel S et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092CrossRefPubMed Gandhi L, Rodríguez-Abreu D, Gadgeel S et al (2018) Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 378(22):2078–2092CrossRefPubMed
23.
Zurück zum Zitat Paz-Ares L, Ciuleanu TE, Cobo M et al (2021) First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial [published correction appears in Lancet Oncol. 2021 Mar;22(3):e92]. Lancet Oncol 22(2):198–211 Paz-Ares L, Ciuleanu TE, Cobo M et al (2021) First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial [published correction appears in Lancet Oncol. 2021 Mar;22(3):e92]. Lancet Oncol 22(2):198–211
24.
Zurück zum Zitat Peleg Hasson S, Arnold J, Merdler I et al (2021) Cancer therapeutics-related cardiac dysfunction in patients treated with immune checkpoint inhibitors: an understudied manifestation. J Immunother 44(5):179–184CrossRefPubMed Peleg Hasson S, Arnold J, Merdler I et al (2021) Cancer therapeutics-related cardiac dysfunction in patients treated with immune checkpoint inhibitors: an understudied manifestation. J Immunother 44(5):179–184CrossRefPubMed
25.
Zurück zum Zitat Cardinale D, Colombo A, Sandri MT et al (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114(23):2474–2481CrossRefPubMed Cardinale D, Colombo A, Sandri MT et al (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114(23):2474–2481CrossRefPubMed
26.
Zurück zum Zitat Petricciuolo S, Delle Donne MG, Aimo A, Chella A, De Caterina R (2021) Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors. Eur J Clin Investig 51(4):e13400CrossRef Petricciuolo S, Delle Donne MG, Aimo A, Chella A, De Caterina R (2021) Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors. Eur J Clin Investig 51(4):e13400CrossRef
27.
Zurück zum Zitat Waliany S, Neal JW, Reddy S et al (2021) Myocarditis surveillance with high-sensitivity troponin i during cancer treatment with immune checkpoint inhibitors. JACC CardioOncol 3(1):137–139CrossRefPubMedPubMedCentral Waliany S, Neal JW, Reddy S et al (2021) Myocarditis surveillance with high-sensitivity troponin i during cancer treatment with immune checkpoint inhibitors. JACC CardioOncol 3(1):137–139CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Rini BI, Moslehi JJ, Bonaca M et al (2022) Prospective cardiovascular surveillance of immune checkpoint inhibitor-based combination therapy in patients with advanced renal cell cancer: data from the phase III JAVELIN Renal 101 trial [published online ahead of print, 2022 Mar 3]. J Clin Oncol JCO2101806 Rini BI, Moslehi JJ, Bonaca M et al (2022) Prospective cardiovascular surveillance of immune checkpoint inhibitor-based combination therapy in patients with advanced renal cell cancer: data from the phase III JAVELIN Renal 101 trial [published online ahead of print, 2022 Mar 3]. J Clin Oncol JCO2101806
Metadaten
Titel
The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors
verfasst von
Barliz Waissengein
Bian Abu Ata
Ofer Merimsky
Sivan Shamai
Ido Wolf
Joshua H. Arnold
Tali Bar-On
Shmuel Banai
Shafik Khoury
Michal Laufer-Perl
Publikationsdatum
27.10.2022
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Research in Cardiology / Ausgabe 3/2023
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-022-02118-8

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