Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.

Détails

ID Serval
serval:BIB_0F6749D7DFF3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.
Périodique
Leukemia Research
Auteur(s)
Gotta V., Bouchet S., Widmer N., Schuld P., Decosterd L.A., Buclin T., Mahon F.X., Csajka C., Molimard M.
ISSN
1873-5835 (Electronic)
ISSN-L
0145-2126
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
38
Numéro
7
Pages
764-772
Langue
anglais
Résumé
This observational study analyzed imatinib pharmacokinetics and response in 2478 chronic myeloid leukemia (CML) patients. Data were obtained through centralized therapeutic drug monitoring (TDM) at median treatment duration of ≥2 years. First, individual initial trough concentrations under 400mg/day imatinib starting dose were estimated. Second, their correlation (C^min(400mg)) with reported treatment response was verified. Low imatinib levels were predicted in young male patients and those receiving P-gp/CYP3A4 inducers. These patients had also lower response rates (7% lower 18-months MMR in male, 17% lower 1-year CCyR in young patients, Kaplan-Meier estimates). Time-point independent multivariate regression confirmed a correlation of individual C^min(400mg) with response and adverse events. Possibly due to confounding factors (e.g. dose modifications, patient selection bias), the relationship seemed however flatter than previously reported from prospective controlled studies. Nonetheless, these observational results strongly suggest that a subgroup of patients could benefit from early dosage optimization assisted by TDM, because of lower imatinib concentrations and lower response rates.
Pubmed
Web of science
Création de la notice
23/05/2014 15:59
Dernière modification de la notice
20/08/2019 12:36
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