Startseite Quantitation of cardiac troponin I in cancer patients treated with immune checkpoint inhibitors: a case-control study
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Quantitation of cardiac troponin I in cancer patients treated with immune checkpoint inhibitors: a case-control study

  • Antigona Ulndreaj , Davor Brinc , Mehmet Altan , Oscar D. Pons-Belda , Amaia Fernandez-Uriarte , Hong Mu-Mosley , Farjana Fattah , Mitchell S. von Itzstein , Antoninus Soosaipillai , Vathany Kulasingam , Nicolas L. Palaskas , David E. Gerber , Eleftherios P. Diamandis ORCID logo , John V. Heymach und Ioannis Prassas EMAIL logo
Veröffentlicht/Copyright: 27. Oktober 2022
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 61 Heft 1

Abstract

Objectives

Immune checkpoint inhibitors (ICIs) cause a variety of toxicities, including immune-related adverse events (irAEs), but there are no biomarkers to predict their development. Guidelines recommend measuring circulating cardiac troponin I (cTnI) during ICI therapy to detect related cardiotoxicities. Moreover, elevated cTnI has also been associated with worse outcomes in non-cardiac patients, including cancer. Thus here, we investigated whether cTnI levels were higher in patients with irAEs.

Methods

The study consisted of three groups; 21 cancer patients undergoing ICI immunotherapies who presented with irAEs, four patients without irAEs, and 20 healthy controls. Patient samples were assessed at baseline (n=25), during ICI treatment (n=25, median=6 weeks of treatment) and at toxicity (n=6, median=13 weeks of treatment). In addition to blood high sensitivity cardiac troponin I (hs-cTnI), anti-thyroglobulin (TG) and anti-thyroid peroxidase (TPO) antibodies were also quantitated to detect thyroid dysfunction, constituting the second leading toxicity (23.8%) after pneumonitis (28.6%).

Results

Four patients with irAEs (n=4/21; 19%) and one without irAEs (n=1/4; 25%) showed higher hs-cTnI levels at any time-point; the remaining had physiological levels. None of these patients developed cardiotoxicity. Concurrent elevated levels of anti-thyroid antibodies and hs-cTnI were detected in one patient with thyroid dysfunction (n=1/5, 20%). However, these antibodies were also elevated in three patients (n=3/16, 19%) with non-thyroid irAEs and in up to 40% of healthy controls.

Conclusions

hs-cTnI was not elevated in patients with irAEs, but larger studies are needed to confirm these observations.

Keywords: anti-thyroid autoantibodies; cancer immunotherapy; cardiac troponin I; case-control study; immune checkpoint inhibitors; immune-related adverse events; predictive biomarkers; prognostic biomarkers
Corresponding author: Dr. Ioannis Prassas, PhD, Mount Sinai Hospital, Joseph & Wolf Lebovic Ctr., 60 Murray St [Box 32], Flr 6 - Rm L6-201 Toronto, ON, M5T 3L9, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada, Phone: 416-586-8443, Fax: 416-619-5521, E-mail:

  1. Research funding: Dr. Ulndreaj is supported by a post-doctoral fellowship from the University of Toronto’s Medicine by Design initiative, which receives funding from the Canada First Research Excellence Fund (CFREF). We would like to acknowledge Anselmo Fabros and Fatimah Zuraiqi for their technical assistance.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Dr. Eleftherios P. Diamandis declares that he holds an advisory role with Abbott Diagnostics and a consultant role with Imaware Diagnostics. Dr. Palaskas is supported by the NIH/NCI 1P01CA261669-01, the Cancer Prevention & Research Institute of Texas (RP200670), the Sabin Family Foundation Fellowship, and the MD Anderson Department of Internal Medicine Research Development Award, and has a consulting role with Replimmune and Kiniksa. Dr. Altan receives research funding (to institution) from Genentech, Nektar Therapeutics, Merck, GlaxoSmithKline, Novartis, Jounce Therapeutics, Bristol Myers Squibb, Eli Lilly, Adaptimmune, Shattuck Lab, Gilead, and holds an advisory role with GlaxoSmithKline, Shattuck Lab, Bristol Myers Squibb, AstraZeneca. Dr. Heymach receives research support from GlaxoSmithKline, Shattuck Lab, Bristol Myers Squibb, AstraZeneca and holds an advisory role with AstraZeneca, EMD Serono, Boehringer-Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Hengrui Therapeutics, Eli Lilly, Spectrum (receives royalties and licensing fees), Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, Pneuma Respiratory, Kairos Venture Investments, Roche, Leads Biolabs, RefleXion, Chugai Pharmaceuticals.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013) and has been approved by the authors’ Institutional Review Boards (Mount Sinai Hospital protocol # 18-0077-E; University of Texas MD Anderson Cancer Center protocol # 2017-0311; University of Texas Southwestern Medical Center protocol #STU 082015-053). Patients provided written, informed consent for additional data collection, presentation, and publication.

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Received: 2022-05-16
Accepted: 2022-09-21
Published Online: 2022-10-27
Published in Print: 2023-01-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. A new milestone on the road to global standardization of apolipoprotein measurements
  4. Review
  5. Saliva – a new opportunity for fluid biopsy
  6. Opinion Papers
  7. Emerging technology: a definition for laboratory medicine
  8. The next wave of innovation in laboratory automation: systems for auto-verification, quality control and specimen quality assurance
  9. EFLM Paper
  10. The new, race-free, Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation to estimate glomerular filtration rate: is it applicable in Europe? A position statement by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)
  11. Guidelines and Recommendations
  12. Overcoming challenges regarding reference materials and regulations that influence global standardization of medical laboratory testing results
  13. General Clinical Chemistry and Laboratory Medicine
  14. Quantitative protein mass-spectrometry requires a standardized pre-analytical phase
  15. Report from the HarmoSter study: inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone
  16. The influence of proteoforms: assessing the accuracy of total vitamin D-binding protein quantification by proteolysis and LC-MS/MS
  17. Total serum vitamin B12 (cobalamin) LC-MS/MS assay as an arbiter of clinically discordant immunoassay results
  18. The preanalytical process in the emergency department, a European survey
  19. Proenkephalin A as a marker for glomerular filtration rate in critically ill children: validation against gold standard iohexol GFR measurements
  20. Umbilical cord blood gases: probability of arterial or venous source in acidemia
  21. Reference Values and Biological Variations
  22. Pediatric reference interval verification for 17 specialized immunoassays and cancer markers on the Abbott Alinity i system in the CALIPER cohort of healthy children and adolescents
  23. Hematology and Coagulation
  24. Performance of digital morphology analyzer CellaVision DC-1
  25. Cancer Diagnostics
  26. Managing the impact of inter-method bias of prostate specific antigen assays on biopsy referral: the key to move towards precision health in prostate cancer management
  27. Cardiovascular Diseases
  28. Quantitation of cardiac troponin I in cancer patients treated with immune checkpoint inhibitors: a case-control study
  29. Infectious Diseases
  30. A novel scoring system combining Modified Early Warning Score with biomarkers of monocyte distribution width, white blood cell counts, and neutrophil-to-lymphocyte ratio to improve early sepsis prediction in older adults
  31. Technical and health governance aspects of the External Quality Assessment Scheme for the SARS-CoV-2 molecular tests: institutional experience performed in all clinical laboratories of a Regional Health Service
  32. Acknowledgment
  33. Acknowledgment
  34. Letters to the Editor
  35. About the estimation of albuminuria based on proteinuria results
  36. Response to “About the estimation of albuminuria based on proteinuria results”
  37. Reply to Abildgaard et al.: lot variation and inter-device differences contribute to poor analytical performance of the DCA vantage™ HbA1c POCT instrument in a true clinical setting
  38. Reply to letter from Mayfield et al. regarding “Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA1c POCT instrument in a true clinical setting”
  39. High-sensitive cardiac troponin T: are turbulences coming?
  40. Analytical performance evaluation of bioactive adrenomedullin on point-of-care platform
  41. Increased PD-L1 surface expression on peripheral blood granulocytes and monocytes after vaccination with SARS-CoV2 mRNA or vector vaccine
  42. Neopterin level can be measured by intraocular liquid biopsy
  43. The stability of pleural fluid pH under slushed ice and room temperature conditions
https://doi.org/10.1515/cclm-2022-0471
Schlagwörter für diesen Artikel
anti-thyroid autoantibodies; cancer immunotherapy; cardiac troponin I; case-control study; immune checkpoint inhibitors; immune-related adverse events; predictive biomarkers; prognostic biomarkers

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. A new milestone on the road to global standardization of apolipoprotein measurements
  4. Review
  5. Saliva – a new opportunity for fluid biopsy
  6. Opinion Papers
  7. Emerging technology: a definition for laboratory medicine
  8. The next wave of innovation in laboratory automation: systems for auto-verification, quality control and specimen quality assurance
  9. EFLM Paper
  10. The new, race-free, Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation to estimate glomerular filtration rate: is it applicable in Europe? A position statement by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)
  11. Guidelines and Recommendations
  12. Overcoming challenges regarding reference materials and regulations that influence global standardization of medical laboratory testing results
  13. General Clinical Chemistry and Laboratory Medicine
  14. Quantitative protein mass-spectrometry requires a standardized pre-analytical phase
  15. Report from the HarmoSter study: inter-laboratory comparison of LC-MS/MS measurements of corticosterone, 11-deoxycortisol and cortisone
  16. The influence of proteoforms: assessing the accuracy of total vitamin D-binding protein quantification by proteolysis and LC-MS/MS
  17. Total serum vitamin B12 (cobalamin) LC-MS/MS assay as an arbiter of clinically discordant immunoassay results
  18. The preanalytical process in the emergency department, a European survey
  19. Proenkephalin A as a marker for glomerular filtration rate in critically ill children: validation against gold standard iohexol GFR measurements
  20. Umbilical cord blood gases: probability of arterial or venous source in acidemia
  21. Reference Values and Biological Variations
  22. Pediatric reference interval verification for 17 specialized immunoassays and cancer markers on the Abbott Alinity i system in the CALIPER cohort of healthy children and adolescents
  23. Hematology and Coagulation
  24. Performance of digital morphology analyzer CellaVision DC-1
  25. Cancer Diagnostics
  26. Managing the impact of inter-method bias of prostate specific antigen assays on biopsy referral: the key to move towards precision health in prostate cancer management
  27. Cardiovascular Diseases
  28. Quantitation of cardiac troponin I in cancer patients treated with immune checkpoint inhibitors: a case-control study
  29. Infectious Diseases
  30. A novel scoring system combining Modified Early Warning Score with biomarkers of monocyte distribution width, white blood cell counts, and neutrophil-to-lymphocyte ratio to improve early sepsis prediction in older adults
  31. Technical and health governance aspects of the External Quality Assessment Scheme for the SARS-CoV-2 molecular tests: institutional experience performed in all clinical laboratories of a Regional Health Service
  32. Acknowledgment
  33. Acknowledgment
  34. Letters to the Editor
  35. About the estimation of albuminuria based on proteinuria results
  36. Response to “About the estimation of albuminuria based on proteinuria results”
  37. Reply to Abildgaard et al.: lot variation and inter-device differences contribute to poor analytical performance of the DCA vantage™ HbA1c POCT instrument in a true clinical setting
  38. Reply to letter from Mayfield et al. regarding “Lot variation and inter-device differences contribute to poor analytical performance of the DCA Vantage™ HbA1c POCT instrument in a true clinical setting”
  39. High-sensitive cardiac troponin T: are turbulences coming?
  40. Analytical performance evaluation of bioactive adrenomedullin on point-of-care platform
  41. Increased PD-L1 surface expression on peripheral blood granulocytes and monocytes after vaccination with SARS-CoV2 mRNA or vector vaccine
  42. Neopterin level can be measured by intraocular liquid biopsy
  43. The stability of pleural fluid pH under slushed ice and room temperature conditions
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