title: Early onset hypercholesterolemia induced by the 2nd-generation tyrosine kinase inhibitor nilotinib in patients with chronic phase-chronic myeloid leukemia.
abstract: Despite a well-recognized clinical benefit of the 2(nd)-generation tyrosine kinase inhibitor nilotinib in patients with imatinib-resistant/-intolerant or newly diagnosed chronic myeloid leukemia, recent evidence suggests that nilotinib has a propensity to increase the risk of occlusive arterial events, especially in patients with pre-existing cardiovascular risk factors. Given the key role of lipids in cardiovascular diseases, we studied the plasma lipid profile and global cardiovascular risk prior to and during nilotinib therapy in a series of 27 patients in the setting of a prospective single center study. Data from a minimum 1-year follow up showed that nilotinib significantly increased total, low- and high-density lipoprotein cholesterol within three months. Consequently, the proportion of patients with non-optimal low-density lipoprotein cholesterol increased from 48.1% to 88.9% by 12 months, leading to cholesterol-lowering drug intervention in 22.2% of patients. The proportion of patients with low levels of high-density lipoprotein cholesterol decreased from 40.7% to 7.4% by 12 months. In contrast, a significant decrease in triglycerides was observed. Global cardiovascular risk worsened in 11.1% of patients due to diabetes or occlusive arterial events. Whether hypercholesterolemia was the main driver of occlusive arterial events was uncertain: a longer follow up is necessary to ask whether nilotinib-induced hypercholesterolemia increases long-term risk of atherosclerotic diseases. Nevertheless, given key atherogenic properties of low-density lipoprotein cholesterol, we conclude that when prescribing nilotinib, commitment to detect lipid disorders at baseline and during follow up is mandatory given their frequency, requirement for changes in lifestyle or drug intervention, and potential for long-term cardiovascular complications.
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, AP-HP, Paris delphine.rea@sls.aphp.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.affiliation: Service de Médecine Vasculaire and INSERM UMR970, PARCC, Hôpital Européen Georges Pompidou, AP-HP, Paris.
authors.forename: Tristan
authors.initials: T
authors.lastname: Mirault
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, AP-HP, Paris.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cluzeau
authors.affiliation: Service de Diabétologie et d'Endocrinologie, Hôpital Lariboisière, AP-HP, Paris.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gautier
authors.affiliation: INSERM Centre d'Investigation Clinique 1402, CHU de Poitiers, France.
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.affiliation: Service d'Hématologie Adulte, Hôpital Saint-Louis, AP-HP, Paris.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Service de Médecine Vasculaire and INSERM UMR970, PARCC, Hôpital Européen Georges Pompidou, AP-HP, Paris.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Messas
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D015466:Leukemia, Myeloid, Chronic-Phase / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C498826:nilotinib