title: The clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study.
abstract: This retrospective multicenter study in patients with chronic myeloid leukemia in chronic phase was undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinib plasma measurements, were analyzed during treatment with imatinib given at a fixed 400mg daily dose. A significant inverse relationship of imatinib concentration with the patients' weight was observed (Pearson's test: p=0.02, R2=0.1). More interestingly, patients with poor response (switched to another tyrosine kinase inhibitor because of imatinib failure, or because of disease progression after an initial response) displayed a significantly lower mean imatinib concentration as compared to patients maintained on imatinib (822ng/mL vs 1099ng/mL; Student's t-test, p=0.04). Failure or disease progression occurred more often in patients in the lowest quartile of imatinib concentrations compared to patients in the highest quartile (p=0.02, logrank test). No correlation could be established with other biological or clinical parameter, including complete cytogenic response and major molecular response.
  
  
  CONCLUSIONS
  in patients treated with imatinib at a fixed daily dose of 400mg, imatinib plasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitor due to imatinib failure. Systematic determination of imatinib plasma trough levels should be encouraged in such patients.
authors.affiliation: Hematology Department of CH Jolimont, La Louvière, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Van Obbergh
authors.affiliation: Hematology Department of Cliniques, Universitaires St Luc, Brussels, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Knoops
authors.affiliation: Hematology Department of UZ Leuven, Belgium.
authors.forename: Timothy
authors.initials: T
authors.lastname: Devos
authors.affiliation: Hematology Department of CHU Liège, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
authors.affiliation: Hematology Department of CHU Dinant Godinne, Belgium.
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.affiliation: Hematology Department of CHU Erasme, Brussels, Belgium.
authors.forename: Fleur
authors.initials: F
authors.lastname: Benghiat
authors.affiliation: Hematology Department of CHWAPI, Tournai, Belgium.
authors.forename: Khalil
authors.initials: K
authors.lastname: Kargar-Samani
authors.affiliation: Hematology Department of Clinique St Jean, Brussels, Belgium.
authors.forename: Deborah
authors.initials: D
authors.lastname: Bauwens
authors.affiliation: Hematology Department of CHU Brugmann, Brussels, Belgium.
authors.forename: André
authors.initials: A
authors.lastname: Efira
authors.affiliation: Hematology Department of Cliniques de l'Europe, Brussels, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Dubois
authors.affiliation: Hematology Department of CHU Tivoli, La Louvière, Belgium.
authors.forename: Cécile
authors.initials: C
authors.lastname: Springael
authors.affiliation: Hematology Department of St Luc, Bouge, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Montfort
authors.affiliation: Hematology Department of St Pierre, Ottignies, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Connerotte
authors.affiliation: Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Capron
authors.affiliation: Hematology Department of CH Jolimont, La Louvière, Belgium. Electronic address: adelannoy222@gmail.com.
authors.forename: André
authors.initials: A
authors.lastname: Delannoy
authors.affiliation: Clinical Chemistry Department, Cliniques Universitaires St Luc, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001530:Belgium; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000068877:Imatinib Mesylate
keywords: Chronic myeloid leukemia; Imatinib mesylate; Therapeutic drug monitoring