Korean Journal of Clinical Pharmacy (한국임상약학회지)

Korean College Of Clinical Pharmacy (한국임상약학회)
권호 표지
DOI QR코드

DOI QR Code

Analysis of Pembrolizumab-induced Blood Glucose Level Change in Cancer Patients

암환자에서 Pembrolizumab 투여로 인한 혈당수치 변화 분석

  • Jung, Hee Yoon (College of Pharmacy, Chungnam National University) ;
  • Hong, Min-Soo (College of Pharmacy, Chungnam National University) ;
  • Jung, Woo Jin (College of Pharmacy, Chungnam National University) ;
  • Choi, Sun Ok (College of Pharmacy, Chungnam National University) ;
  • Chae, Jung-woo (College of Pharmacy, Chungnam National University) ;
  • Yun, Hwi-yeol (College of Pharmacy, Chungnam National University)
  • Received : 2021.09.09
  • Accepted : 2021.09.19
  • Published : 2021.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Pembrolizumab, an anti-cancer drug, is known to increase the activity of the immune system, leading to side effects called immune-related adverse events (irAE), including type 1 diabetes. This study analyzed the correlation between blood glucose level and pembrolizumab administration and investigated the covariates that affect those changes in cancer treatment. Methods: The information of 133 adult cancer patients was obtained from the electronic medical record (EMR) to identify the changes in random blood glucose (RBG) levels during the pembrolizumab treatment. Subjects were classified into subgroups according to their baseline RBG level, history of diabetes, and the use of steroids, and linear regression analysis was conducted. In addition, a secondary analysis was performed within the group of subjects having a strong correlation to glycemic change, which was based on the Pearson correlation coefficient being less than -0.7 or greater than +0.7. Univariate and multivariate logistic regressions were conducted to identify the risk factors to glycemic increase. Results: The RBG level tended to descend without significant differences in total patients during the administration period of pembrolizumab. Despite the insignificance, the logistic regression analysis presents that the odds ratios of baseline RBG less than 130 mg/dL, prophylactic steroid use, and higher dose of pembrolizumab per cycle (mg/kg/cycle) were greater than 1. Conclusions: Prophylactic administration of steroids and a higher dose of pembrolizumab per cycle may increase the blood glucose level as irAE in cancer patients with a strong tendency to glycemic change.

Keywords

Acknowledgement

이 논문은 충남대학교 학술연구비 및 2020년도 정부(과학기술정보통신부)의 재원으로 정보통신기획평가원(No. 2020-0-01441, 인공지능융합연구센터(충남대학교))의 지원을 받아 수행된 연구입니다.

References

  1. Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol 2012;23(Suppl 8):viii6-9. https://doi.org/10.1093/annonc/mds256
  2. Thompson JA, Schneider BJ, Brahmer J, et al. NCCN guidelines insights: Management of immunotherapy-related toxicities, Version 1.2020. J Natl Compr Canc Netw 2020;18(3):230-41. https://doi.org/10.6004/jnccn.2020.0012
  3. US Food and Drug Administration. Drug approval package: pembrolizumab [online]. 2020. Available from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125514Orig1s000TOC.cfm. Accessed November 20, 2020.
  4. US Food and Drug Administration. Drug approval package: nivolumab [online]. 2020. Available from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125554Orig1s000TOC.cfm. Accessed November 20, 2020.
  5. US Food and Drug Administration. Drug approval package: atezolizumab [online]. 2020. Available from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761034Orig1s000TOC.cfm. Accessed November 20, 2020.
  6. US Food and Drug Administration. Drug approval package: ipilimumab [online]. 2020. Available from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125377orig1s000toc.cfm. Accessed November 20, 2020.
  7. US Food and Drug Agency. Drug approval package: durvalumab [online]. 2020. Available from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761069Orig1s000TOC.cfm. Accessed November 20, 2020.
  8. Day D, Hansen AR. Immune-related adverse events associated with immune checkpoint inhibitors. BioDrugs 2016;30(6):571-84. https://doi.org/10.1007/s40259-016-0204-3
  9. Liu YH, Zang XY, Wang JC, Huang SS, Xu J, Zhang P. Diagnosis and management of immune related Adverse events (irAEs) in cancer immunotherapy. Biomed Pharmacother 2019;120:109437. https://doi.org/10.1016/j.biopha.2019.109437
  10. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12(4):252-64. https://doi.org/10.1038/nrc3239
  11. Mok, TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. The Lancet 2019;393(10183):1819-30. https://doi.org/10.1016/S0140-6736(18)32409-7
  12. Bonaventura A, Montecucco F. Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review. Diabetes Res Clin Pract 2018;139:203-20. https://doi.org/10.1016/j.diabres.2018.03.006
  13. Barroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and meta-analysis. JAMA Oncol 2018;4(2):173-82. https://doi.org/10.1001/jamaoncol.2017.3064
  14. Clotman K, Janssens K, Specenier P, Weets I, De Block CEM. Programmed cell death-1 inhibitor-induced type 1 diabetes mellitus. J Clin Endocrinol Metab 2018;103(9):3144-54. https://doi.org/10.1210/jc.2018-00728
  15. World Health Organization, International Diabetes Institute, International Association for the Study of Obesity (IASO). The Asia-Pacific perspective: redefining obesity and its treatment. Sydney: Health Communications Australia. Available from https://apps.who.int/iris/handle/10665/206936. Accessed September 10, 2021.
  16. Tatsuno I, Sugiyama T. Glucocorticoid-induced diabetes mellitus is a risk for vertebral fracture during glucocorticoid treatment. Diabetes Res Clin Pract 2011;93(1):e18-20. https://doi.org/10.1016/j.diabres.2011.03.005
  17. de Filette JMK, Pen JJ, Decoster L, et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol 2019;181(3):363-74. https://doi.org/10.1530/EJE-19-0291
  18. Korea Diabetes Association, Clinical Practice Guidelines for Diabetes 2021. Available from https://www.diabetes.or.kr/pro/publish/guide.php?code=guide&number=853&mode=view. Accessed September 10, 2021.
  19. Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D, Davidson MB. A new look at screening and diagnosing diabetes mellitus. J Clin Endocrinol Metab 2008;93(7):2447-53. https://doi.org/10.1210/jc.2007-2174
  20. Magis Q, Gaudy-Marqueste C, Basire A, et al. Diabetes and blood glucose disorders under anti-PD1. J Immunother 2018;41(5):232-40. https://doi.org/10.1097/CJI.0000000000000218