Evaluation of Imatinib Concentrations in Samples Submitted for BCR-ABL1 or Imatinib Testing-Evidence to Support Therapeutic Drug Monitoring for Dose Optimization? Ther Drug Monit 2020 Aug;42(4):559-564
Date
07/23/2020Pubmed ID
32697563DOI
10.1097/FTD.0000000000000771Scopus ID
2-s2.0-85088425609 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
BACKGROUND: Imatinib is one of the first-line therapies for chronic myeloid leukemia. Achieving a major molecular response early in treatment, as indicated by a BCR-ABL1 major international scale result of ≤0.1% within 6 months, is associated with better patient outcomes and is statistically associated with a trough imatinib concentration of approximately 1000 ng/mL. Adherence to therapy, drug resistance, drug-drug interactions, and pharmacokinetic/pharmacodynamic factors may hinder attaining this target. Therapeutic drug monitoring of imatinib is not currently standard-of-care, but may help to evaluate adherence and optimize treatment of patients with chronic myeloid leukemia. This study aimed to evaluate imatinib concentrations in real-world patient plasma samples to identify the proportion of imatinib-treated patients who achieved the therapeutic target of 1000 ng/mL.
METHODS: This was a retrospective, observational study that measured imatinib in residual plasma samples used for BCR-ABL1 tests (n = 1022) and analyzed clinician-ordered imatinib tests for therapeutic drug monitoring (n = 116). Imatinib was measured by competitive immunoassay. The frequency of imatinib concentrations achieving the therapeutic target was determined and correlated with BCR-ABL1 major international scale, age, and sex.
RESULTS: Seventy-two percent of patients tested for BCR-ABL1 may not have been prescribed or were not adherent to imatinib therapy. In the 29% of patients who did not achieve major molecular response, but had quantifiable imatinib concentrations, the therapeutic concentration was not met. For clinician-ordered imatinib tests, 45% of samples did not exceed the therapeutic target and 4% had potentially toxic plasma concentrations (>3000 ng/mL).
CONCLUSIONS: Therapeutic drug monitoring for imatinib may assist clinicians in the identification of patients who may not be adherent to therapy, display variable pharmacokinetics or pharmacodynamics, or may be experiencing toxicity or treatment failure.
Author List
Smy L, Sadler AJ, McMillin GAAuthor
Laura Smy PhD Assistant Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAntineoplastic Agents
Drug Monitoring
Female
Fusion Proteins, bcr-abl
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Male
Middle Aged
Retrospective Studies
