Imatinib trough plasma levels do not correlate with the response to therapy in patients with chronic myeloid leukemia in routine clinical setting.
Association of trough imatinib plasma levels (IPL) with cytogenetic or molecular response to treatment in patients with chronic myeloid leukemia (CML) was repeatedly reported. We analyzed their value in the routine clinical setting in 131 patients with chronic phase CML in whom imatinib was applied as first- or second-line treatment. A total of 1,118 measurements were obtained by ultra-performance liquid chromatography-tandem mass spectrometry assay in patients treated with daily dose of imatinib ranging from 100 to 800 mg. Samples were obtained from 1 to 96 h after drug ingestion. High inter (36%) and intraindividual variability (9-33%) of IPL was observed. For analysis of correlation of IPL with treatment response, two sets of samples were selected according to the European LeukemiaNet (ELN) criteria. The first set consisted of 241 samples taken 24 ± 2 h after dosing in 54 patients, and the second one consisted of 329 samples taken 24 ± 4 h after imatinib ingestion in 84 patients. In both sets, only patients treated with 400 mg imatinib once daily for at least 18 months were included. From multiple measurements in individual patients, mean IPL were used. In both sets, we were not able to demonstrate a statistically significant correlation between IPL and response to treatment according to the ELN. We believe that this was due to the differences in patients' compliance, leukemia biology, and other variables that are difficult to eliminate in the routine clinical practice. The use of IPL for prognostic estimation in CML treatment outside the clinical trials is probably limited.
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc, University Hospital Olomouc, Czech Republic. edgar.faber@fnol.cz
Edgar
E
Faber
David
D
Friedecký
Kateřina
K
Mičová
Sárka
S
Rožmanová
Martina
M
Divoká
Marie
M
Jarošová
Karel
K
Indrák
Tomáš
T
Adam
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001549:Benzamides; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000097:blood; D001774:Blood Chemical Analysis; D019411:Clinical Laboratory Techniques; D003955:Diagnostic Tests, Routine; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D011743:Pyrimidines / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D054316:Biomarkers, Pharmacological; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate