Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10908817 | Leukemia Research | 2014 | 9 Pages |
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 â¥2 years. First, individual initial trough concentrations under 400 mg/day imatinib starting dose were estimated. Second, their correlation (CËmin(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 CËmin(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.
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Authors
Verena Gotta, Stephane Bouchet, Nicolas Widmer, Peter Schuld, Laurent A. Decosterd, Thierry Buclin, Francois-Xavier Mahon, Chantal Csajka, Mathieu Molimard,