title: Therapeutic drug monitoring of imatinib in chronic myeloid leukemia: experience from 1216 patients at a centralized laboratory.
abstract: This study set out to examine in a large real-life cohort of patients with chronic myeloid leukemia (CML) the impact of imatinib threshold of 1000 ng/mL on molecular response, as suggested in a small subset of patients. Patient plasma samples were submitted from around France to a central facility, free of charge under the auspices of the European Treatment and Outcome Study (EUTOS) for CML. Submitting physicians were required to complete an 'imatinib monitoring request form', including details of why therapeutic drug monitoring (TDM) was requested, dose and duration of imatinib treatment, cytogenetic and molecular response, adverse events, and concurrent medications. Imatinib trough plasma concentration (C(min)) was measured at the central facility. Among 1985 eligible plasma samples analyzed, from 1216 CML patients, imatinib C(min) correlated positively with reported imatinib dose, but interpatient variability in C(min) was high (60%). A logistic regression analysis revealed that treatment duration and imatinib C(min) > 1000 ng/mL were significantly associated with major and complete molecular responses with odds ratios of 1.69 and 2.08, respectively. These data support in real-life setting that imatinib C(min) threshold of 1000 ng/mL is associated with major and complete molecular response and that TDM could play an important role in dose optimization.
authors.affiliation: Univ Bordeaux, F-33000, Bordeaux, France; INSERM U657, F-33000, Bordeaux, France; CHU Bordeaux, F-33000, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bouchet
authors.forename: Karine
authors.initials: K
authors.lastname: Titier
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
authors.forename: Régis
authors.initials: R
authors.lastname: Lassalle
authors.forename: Basmah
authors.initials: B
authors.lastname: Ambrosino
authors.forename: Sylvie
authors.initials: S
authors.lastname: Poulette
authors.forename: Peter
authors.initials: P
authors.lastname: Schuld
authors.forename: Coralie
authors.initials: C
authors.lastname: Belanger
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Mathieu
authors.initials: M
authors.lastname: Molimard
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: chronic myeloid leukemia; drug monitoring; imatinib therapeutic