Cardiotoxicity Associated with Tyrosine Kinase Inhibitors in Philadelphia Chromosome-Positive Leukemias: An Overview of Mechanisms, Clinical Implications, and Management Strategies

Year : 2024 | Volume : 13 | Issue : 03 | Page : 18 24
    By

    Rashmi H. R.,

  • Kishan A,

  • Sunitha M,

  • Ganesh n.s,

  1. Student, Deptment of pharmaceutics, T. John College of Pharmacy, Bengaluru, India
  2. Student, Deptment of pharmaceutics, T. John College of Pharmacy, Bengaluru, India
  3. Assistant professor,, Deptment of pharmaceutics, T. John College of Pharmacy, Bengaluru, India
  4. Professor and Head, Deptment of pharmaceutics, T. John College of Pharmacy, Bengaluru, India

Abstract

Tyrosine kinase inhibitors have greatly enhanced the outlook for individuals diagnosed with Philadelphia chromosome-positive leukemias, including chronic myeloid leukemia and acute lymphoblastic leukemia. However, these therapeutic agents are associated with Cardiotoxicities and can manifest as left ventricular dysfunction, which may progress to heart failure, along with electrocardiographic abnormalities, dysrhythmias, hypertension, myocardial ischemia, and thromboembolic events. The unclear frequency of drug-induced cardiovascular complications, coupled with uncertainties regarding their reversibility and long-term safety, highlights the need for a multidisciplinary approach. This initiative should include collaboration among cardio-oncology specialists, primary care physicians, pharmacologists, and toxicologists. In this context, we focus on the cardiovascular events linked to targeted anticancer therapies by providing a brief overview of the mechanisms behind cardiotoxicity and offering clinical guidance for effective patient management. Cardiotoxicity is a notable concern in the treatment of Ph+ leukemia with Tyrosine kinase inhibitors. Vigilant cardiovascular monitoring, including baseline and periodic assessment of cardiac function, is crucial for early detection and management of cardiotoxic effects. Strategies to mitigate cardiotoxicity include optimizing cardiovascular risk factors and timely therapeutic interventions upon signs of cardiac dysfunction.

Keywords: Tyrosine kinase inhibitors (TKIs), Chronic myeloid leukemia (CML), Acute lymphoblastic leukemia (ALL), Cardio-oncology, Drug-induced cardiovascular complications, Cardiovascular monitoring.

[This article belongs to Research & Reviews: Journal of Oncology and Hematology ]

How to cite this article:
Rashmi H. R., Kishan A, Sunitha M, Ganesh n.s. Cardiotoxicity Associated with Tyrosine Kinase Inhibitors in Philadelphia Chromosome-Positive Leukemias: An Overview of Mechanisms, Clinical Implications, and Management Strategies. Research & Reviews: Journal of Oncology and Hematology. 2024; 13(03):18-24.
How to cite this URL:
Rashmi H. R., Kishan A, Sunitha M, Ganesh n.s. Cardiotoxicity Associated with Tyrosine Kinase Inhibitors in Philadelphia Chromosome-Positive Leukemias: An Overview of Mechanisms, Clinical Implications, and Management Strategies. Research & Reviews: Journal of Oncology and Hematology. 2024; 13(03):18-24. Available from: https://journals.stmjournals.com/rrjooh/article=2024/view=188686


References

  1. Berisha A, Placci A, Piccaluga PP. Cardiovascular toxicity of targeted therapies in hematologic malignancies. 2023;4(1):68–75. doi:10.3390/hemato4010007.
  2. Berisha A, Placci A, Piccaluga PP. Cardiovascular toxicity of targeted therapies in hematologic malignancies. 2023. doi:10.3390/hemato4010007. Corpus ID: 257263317.
  3. Manouchehri A, Kanu E, Mauro MJ, Aday AW, Lindner JR, Moslehi J. Cardiovascular effects of tyrosine kinase inhibitors in chronic myeloid leukemia. Arterioscler Thromb Vasc Biol. 2020;40:301–8.. doi:10.1161/ATVBAHA.119.313353.
  4. Raschi E, De Ponti F. Cardiovascular toxicity of anticancer-targeted therapy: emerging issues in the era of cardio-oncology. Intern Emerg Med. 2011;7(2):113–31. doi:10.1007/s11739-011-0774-Y.
  5. Novo G, Di Lisi D, Fiuza M, Pinto FJ. Cardiovascular damage induced by anti-BCR-ABL tyrosine kinase inhibitors. In: Current Clinical Pathology. Cham: Springer International Publishing; 2019. pp. 45–55. doi:10.1007/978-3-319-93402-0_6.
  6. Grela-Wojewoda A, Pacholczak-Madej R, Adamczyk A, Korman M, Püsküllüoğlu M. Cardiotoxicity induced by protein kinase inhibitors in patients with cancer. Int J Mol Sci. 2022;23(5):2815. doi:10.3390/ijms23052815.
  7. Steegmann JL, Baccarani M, Breccia M, Casado LF, García-Gutiérrez V, Hochhaus A, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukemia. 2016;30(8):1648–71. doi:10.1038/leu.2016.104.
  8. Moslehi JJ, Deininger M. Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol. 2015;33(35):4210–8. doi:10.1200/JCO.2015.62.4718.
  9. Schiffer CA. BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med. 2007;357:258–65.
  10. Gustafson D, Fish JE, Lipton JH, Aghel N. Mechanisms of cardiovascular toxicity of BCR-ABL1 tyrosine kinase inhibitors in chronic myelogenous leukemia. Curr Hematol Malig Rep. 2020;15(1):20–30. doi:10.1007/s11899-020-00560-x.
  11. Marcolino MS, Ribeiro AL, Clementino NCD, Barbosa MM, et al. The use of imatinib mesylate has no adverse effects on heart function: results of a pilot study in patients with chronic myeloid leukemia. Leuk Res. 2011;35(3):317–22. doi:10.1016/j.leukres.2010.07.011.
  12. Grela-Wojewoda A, Pacholczak-Madej R, Adamczyk A, Korman M, Püsküllüoğlu M. Cardiotoxicity induced by protein kinase inhibitors in patients with cancer. Int J Mol Sci. 2022;23(5):2815. doi:10.3390/ijms23052815.
  13. Cirmi S, El Abd A, Letinier L, Navarra M, Salvo F. Cardiovascular toxicity of tyrosine kinase inhibitors used in chronic myeloid leukemia: an analysis of the FDA adverse event reporting system database (FAERS). Cancers (Basel). 2020;12(4):826. doi:10.3390/cancers12040826.
  14. Xu Z, Cang S, Yang T, Liu D. Cardiotoxicity of tyrosine kinase inhibitors in chronic myelogenous leukemia therapy. Hematol Rev. 2009;1(1):e4 doi:10.4081/hr.2009.e4.
  15. Sayegh N, Yirerong J, Agarwal N, Addison D, Fradley M, Cortes J, et al. Cardiovascular toxicities associated with tyrosine kinase inhibitors. Curr Cardiol Rep. 2023;25(4):269–80. doi:10.1007/s11886-023-01845-2.
  16. Samra B, Kantarjian HM, Sasaki K, Alotaibi AS, Konopleva M, O’Brien S, et al. Discontinuation of maintenance tyrosine kinase inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukemia outside of transplant. Acta Haematol. 2021;144(3):285–92. doi:10.1159/000510112.
  17. Chaar M, Kamta J, Ait-Oudhia S. Mechanisms, monitoring, and management of tyrosine kinase inhibitor-associated cardiovascular toxicities. Onco Targets Ther. 2018;11:6227–37. doi:10.2147/OTT.S170138.
  18. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, et al. Nilotinib (formerly AMN107). Blood. 2007;110(10):3540–6. doi:10.1182/blood-2007-03-080689.
  19. Shamroe CL, Comeau JM. Ponatinib: a new tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Pharmacother. 2013;47(11):1540–6. doi:10.1177/1060028013501144.
  20. Li YF, Combes FP, Hoch M, Lorenzo S, Sy SKB, Ho YY. Population pharmacokinetics of asciminib in tyrosine kinase inhibitor-treated patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic and acute phases. Clin Pharmacokinet. 2022;61(10):1393–1403. doi:10.1007/s40262-022-01148-9. Erratum in: Clin Pharmacokinet. 2022;61(10):1475–6. doi:10.1007/s40262-022-01166-7.
  21. Jabbour E, Deininger M, Hochhaus A. Management of adverse events associated with tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia. 2011;25:201–10. doi:10.1038/leu.2010.215.
  22. Grela-Wojewoda A, Pacholczak-Madej R, Adamczyk A, Korman M, Püsküllüoğlu M. Cardiotoxicity induced by protein kinase inhibitors in patients with cancer. Int J Mol Sci. 2022;23(5):2815. doi:10.3390/ijms23052815.
  23. Mikami T, Kato I, Oiki N, Okamoto S, Kamitori T, Tasaka K, et al. A rare case of relapsed pediatric acute lymphoblastic leukemia after hematopoietic stem cell transplantation. J Pediatr Hematol Oncol. 2022;44(2). doi:10.1097/MPH.0000000000002157.
  24. Kantarjian H, Cortes J. Considerations in the management of patients with Philadelphia chromosome-positive chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy. J Clin Oncol. 2011;29(12):1512–6. doi:10.1200/JCO.2010.33.9176.
Regular Issue Subscription Review Article
Volume 13
Issue 03
Received 18/09/2024
Accepted 05/10/2024
Published 18/11/2024
248

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