title: Rapid onset of peripheral artery disease in a chronic myeloid leukemia patient without prior arterial disorder: direct relationship with nilotinib exposure and clinical outcome.
abstract: The second-generation tyrosine kinase inhibitor (TKI) of the BCR-ABL1 oncoprotein nilotinib used in patients with chronic myeloid leukemia is suspected to increase the risk of arterial occlusion, especially in patients with pre-existing cardiovascular risk factors or established cardiovascular diseases. Here, we describe a case of unexpected and rapid onset of symptomatic peripheral artery disease (PAD) associated with silent stenosis of digestive and renal arteries in a nilotinib-treated patient devoid of significant cardiovascular diseases (CVD) risk factor, prior atherosclerotic disease, or other cause of arterial damage. This is the first report to establish a direct relationship between nilotinib exposure and PAD and to reveal that arterial damage is irreversible despite rapid drug withdrawal. However, functional outcome was favorable upon rapid TKI replacement, specific cardiovascular disease management, and development of collateral arterial network.
authors.affiliation: Médecine Vasculaire, Hôpital Européen Georges-Pompidou, AP-HP, Paris, France; Sorbonne Paris Cité, Université Paris Descartes, Paris, France; INSERM U970, PARCC, Paris, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Mirault
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.forename: Arshid
authors.initials: A
authors.lastname: Azarine
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Messas
mesh_terms: D000792:Angiography; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D057915:Drug Substitution; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000209:etiology*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib
keywords: arterial occlusive diseases; leukemia myelogenous chronic BCR-ABL positive; nilotinib; peripheral arterial disease; pharmacovigilance