Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia

Author:

Picard Stephane123,Titier Karine123,Etienne Gabriel4,Teilhet Emmanuelle123,Ducint Dominique123,Bernard Marie-Agnes1,Lassalle Regis1,Marit Gerald256,Reiffers Josy4,Begaud Bernard123,Moore Nicholas123,Molimard Mathieu123,Mahon Francois-Xavier256

Affiliation:

1. Department of Clinical Pharmacology and Toxicology, Centre Hospitalier Universitaire (CHU) de Bordeaux, Bordeaux, France;

2. University Victor Ségalen Bordeaux 2, Bordeaux, France;

3. Institut National de la Santé et de la Recherche Médicale (INSERM) U657, Bordeaux, France;

4. Department of Hematology, the Institut Bergonié, Regional Cancer Center, Bordeaux, France;

5. Department of Hematology and Blood Diseases, CHU de Bordeaux, Bordeaux, France;

6. INSERM E217, Bordeaux, France

Abstract

Abstract 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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