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

Details

Serval ID
serval:BIB_0F6749D7DFF3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.
Journal
Leukemia Research
Author(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
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
38
Number
7
Pages
764-772
Language
english
Abstract
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
Create date
23/05/2014 15:59
Last modification date
20/08/2019 12:36
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