Second generation tyrosine kinase inhibitor therapy associated with significant carotid stenosis onset: A clinical case report and literature review.
Keywords:
tyrosine kinase inhibitors , carotid stenosis , chronic myeloid leukaemiaAbstract
Introduction: Tyrosine kinase inhibitors (TKI) are employed in the treatment of chronic myeloid leukemia (CML). Concerns about cardiovascular side effects have evolved, especially in patients with cardiovascular risk factors. Recommendations published in 2020 stress the need for preventative, biannual peripheral arterial evaluations, but there is no mention of carotid artery surveillance. We describe significant carotid artery stenosis onset in a young patient with CML treated with TKI therapy, without baseline cardiovascular risk factors. Case: A 55-year-old man was diagnosed with CML in 2016 and was prescribed Nilotinib 300 mg twice daily. Anamnesis reported identified a positive family history for cardiovascular disease only. Supra-aortic vessels Doppler ultrasound (DUS) in 2021 confirmed insignificant left internal carotid artery (ICA) stenosis, which increased to ICA stenosis with hemodynamic consequences, observed in 2023. A computed tomography angiography (CTA) confirmed stenotic progression, estimated between 80-85% over a 2-year period. A multidisciplinary team suggested revascularization with carotid endarterectomy (CEA) performed under general anesthesia with instrumental cerebral intraoperative monitoring. The patient had an uneventful post-procedural course and was discharged post-operative day 2. Post-operative 30-day DUS confirmed ongoing technical success.Conclusion: Our case report emphasizes the need for clinician awareness of a potential risk of carotid artery disease onset in patients undergoing Nilotinib therapy, independently of age and baseline cardiovascular risk factors.References
Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008; 22:14-22. doi: 10.1038/sj.leu.2404955.
Geary CG. The story of chronic myeloid leukaemia. Br J Haematol 2000; 110:2-11. doi: 10.1046/j.1365-2141.2000.02137.x.
Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 2000; 105:3–7. doi: 10.1172/JCI9083.
Aghel N, Lipton JH, Atenafu EG, Kim DDH, Delgado DH. Cardiovascular events after exposure to nilotinib in chronic meloid leukemia: long-term follow-up. Clin Lymphoma Myeloma Leuk 2017; 17: 870–878. doi: 10.1016/j.clml.2017.07.006.
Gugliotta G, Castagnetti F, Breccia M, et al. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia. Haematologica 2015; 100:1146–1150. doi: 10.3324/haematol.2015.129221.
Rix U, Hantschel O, Dürnberger G, et al. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 2007; 110: 4055–4063. doi: 10.1182/blood-2007-07-102061.
Le Coutre P, Rea D, Abruzzese E, et al. Severe peripheral arterial disease during nilotinib therapy. J Natl Cancer Inst 2011; 103:1347-1348. doi: 10.1093/jnci/djr292.
Aichberger KJ, Herndlhofer S, Schernthaner GH, et al. Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML. Am J Hematol 2011; 86:533-539. doi: 10.1002/ajh.22037.
Ferguson GG, Eliasziw M, Barr HW, et al. The North American symptomatic carotid endarterectomy trial: surgical results in 1415 patients. Stroke 1999; 30:1751-8. doi: 10.1161/01.str.30.9.1751.
Yoshimura T, Matsuyama W, Kamohara H. Discoidin domain receptor 1: a new class of receptor regulating leukocyte-collagen interaction. Immunol Res 2005; 31:219–230. doi: 10.1385/IR:31:3:219.
Vasiliadis I, Kolovou G, Mikhailidis DP. Cardiotoxicity and Cancer Therapy. Angiology. 2014; 65:369-371. doi: 10.1177/0003319713498298.
Katgı A, Sevindik ÖG, Gökbulut AA, et al. Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion. Clin Appl Thromb Hemost 2015; 21:678-683. doi: 10.1177/1076029614550817.
Alhawiti N, Burbury KL, Kwa FA, et al. The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state. Thromb Res 2016; 145:54–64. doi: 10.1016/j.thromres.2016.07.019.
Hersant J, Gardembas M, Leftheriotis G, Vandeputte P, Abraham P, Henni S. Tyrosine kinase inhibitor-induced carotid stenosis: A case report. Leuk Res Rep 2019 May 25; 12:1001-71. doi: 10.1016/j.lrr.2019.100171.
Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 2020; 34:966-984. doi: 10.1038/s41375-020-0776-2.
Steegmann JL, Baccarani M, Breccia M, et al. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukemia. Leukemia 2016; 30:1648–1671. doi: 10.1038/leu.2016.104.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Alberto Bramucci, Elisa Peretti, Maria Teresa Corsetti, Gabriele Colò, Alberto Guagliano
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.