Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia.
Using high-performance liquid chromatography-tandem mass spectrometry, we assessed trough imatinib plasma levels in 68 patients with chronic myeloid leukemia (CML) who responded or not to standard-dose imatinib, after at least 12 months' treatment. Mean trough imatinib plasma levels were significantly higher in the group with complete cytogenetic response (56 patients) than in the group without (12 patients; P = .03) and higher in the group with major molecular response (MMR) than in the group without (34 patients [1452 +/- 649 ng/mL] versus 34 patients [869 +/- 427 ng/mL]; P < .001). Regarding trough imatinib plasma levels and their discrimination potential for MMR, the area under receiver operating characteristic curve was 0.775, with best sensitivity (77%) and specificity (71%) at a plasma threshold of 1002 ng/mL. Therefore, monitoring of imatinib plasma levels could be very useful for the management of patients with CML or should at least be checked in the case of treatment failure or suboptimal response.
Picard
Stephane
S
Department of Clinical Pharmacology and Toxicology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Titier
Karine
K
Etienne
Gabriel
G
Teilhet
Emmanuelle
E
Ducint
Dominique
D
Bernard
Marie-Agnes
MA
Lassalle
Regis
R
Marit
Gerald
G
Reiffers
Josy
J
Begaud
Bernard
B
Moore
Nicholas
N
Molimard
Mathieu
M
Mahon
Francois-Xavier
FX
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012074:Remission Induction; D017211:Treatment Failure
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate