title: Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia.
abstract: Using high-performance liquid chromatography-tandem mass spectrometry, we assessed trough imatinib plasma levels in 68 patients with chronic myeloid leukemia (CML) who responded or not to standard-dose imatinib, after at least 12 months' treatment. Mean trough imatinib plasma levels were significantly higher in the group with complete cytogenetic response (56 patients) than in the group without (12 patients; P = .03) and higher in the group with major molecular response (MMR) than in the group without (34 patients [1452 +/- 649 ng/mL] versus 34 patients [869 +/- 427 ng/mL]; P < .001). Regarding trough imatinib plasma levels and their discrimination potential for MMR, the area under receiver operating characteristic curve was 0.775, with best sensitivity (77%) and specificity (71%) at a plasma threshold of 1002 ng/mL. Therefore, monitoring of imatinib plasma levels could be very useful for the management of patients with CML or should at least be checked in the case of treatment failure or suboptimal response.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Picard
authors.forename: Karine
authors.initials: K
authors.lastname: Titier
authors.forename: Gabriel
authors.initials: G
authors.lastname: Etienne
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Teilhet
authors.forename: Dominique
authors.initials: D
authors.lastname: Ducint
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Bernard
authors.forename: Regis
authors.initials: R
authors.lastname: Lassalle
authors.forename: Gerald
authors.initials: G
authors.lastname: Marit
authors.forename: Josy
authors.initials: J
authors.lastname: Reiffers
authors.forename: Bernard
authors.initials: B
authors.lastname: Begaud
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
authors.forename: Mathieu
authors.initials: M
authors.lastname: Molimard
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Mahon
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012074:Remission Induction; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate