Pharmacokinetic pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia

• Published in: Leukemia Vol. 23; no. 9; pp. 1537 - 1544
• Main Authors: Cortes, J E, Egorin, M J, Guilhot, F, Molimard, M, Mahon, F-X
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2009; Nature Publishing Group
• Subjects: Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Blood; Cancer; Cancer Research; Chronic myeloid leukemia; Critical Care Medicine; Decisions; Diagnosis; Dosage; Drug dosages; Drug interaction; Drug Interactions; Drug metabolism; Drug therapy; Hematologic and hematopoietic diseases; Hematology; Humans; Imatinib; Imatinib Mesylate; Intensive; Internal Medicine; Intestinal Absorption; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Medication Adherence; Medicine; Medicine & Public Health; Myeloid leukemia; Oncology; Orosomucoid - metabolism; Patients; Pharmacodynamics; Pharmacokinetics; Pharmacology; Piperazines - adverse effects; Piperazines - pharmacokinetics; Piperazines - therapeutic use; Plasma; Protein Binding; Proteins; Pyrimidines - adverse effects; Pyrimidines - pharmacokinetics; Pyrimidines - therapeutic use; review; Treatment Failure; United States; France; United States > US; tyrosine kinase inhibitors; blood-level testing; pharmacokinetics; chronic myeloid leukemia; imatinib; pharmacodynamics; Antineoplastic agent; Imatinib; Pharmacodynamics; Hematology; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Malignant hemopathy; Medical screening; Blood; Myeloproliferative syndrome; Treatment; Pharmacokinetics; Protein-tyrosine kinase; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.88

Imatinib is the current standard of care in the treatment of chronic myeloid leukemia (CML), inducing durable responses and prolonged progression-free survival. However, plasma exposure to the drug from a given dosing regimen can vary widely among patients. Reasons for this may include incomplete adherence, intrinsic variations in the metabolism of imatinib, and drug–drug interactions. Data from two recent studies have shown a correlation between imatinib trough plasma concentration and clinical response, leading to suggestions that maintaining imatinib blood concentrations above ∼1000 ng/ml might be associated with improved outcomes. In patients who do not respond as well as expected to initial imatinib treatment, measurement of trough plasma concentration could assist with decisions about whether to increase the dose. Blood-level testing may also be helpful in other clinical scenarios: for example, when poor adherence is suspected, adverse reactions are unusually severe, or there is a possible drug–drug interaction. Further work is required to confirm prospectively the link between imatinib plasma concentrations and response, and to define effective trough concentrations in different patient populations. However, based on the current data, imatinib blood-level testing seems to be a useful aid when making clinical decisions in CML.