Retrospective Study of Trough Imatinib Plasma Levels Conducted as Part of the Follow-up of Patients with Chronic Myeloid Leukemia in a Canadian Cohort
Bibliographic record
Abstract
Abstract While imatinib biodisponibility is excellent, trough imatinib plasma levels associated with standard dose imatinib are variable and cannot be predicted by the age, the body surface area or the weight of the patient. Imatinib trough levels have recently been associated with both cytogenetic and molecular responses, making imatinib pharmacokinetics a possible target in optimisation of the treatment of patients with chronic myeloid leukemia. We retrospectively analysed trough imatinib plasma levels prescribed as part of the longitudinal follow-up of a cohort of patients with chronic myeloid leukemia in Canada. Indications for testing were inadequate response, important side effects or suspicion of non compliance. The objectives of the study were to evaluate the variability of trough imatinib plasma levels in our cohort and determine the impact a first result had on the subsequent plasma level in patients with more than one imatinib plasma determination. Analyses of trough plasma levels in 278 patients were conducted in a central canadian laboratory from April 2007 to April 2008. Trough imatinib plasma levels were measured using liquid chromatography and tandem mass spectrometry (LC/MS/MS) with deuterated imatinib as the internal standard. Distribution of trough imatinib plasma levels according to the established IRIS quartiles (Q1–Q4; BLOOD. 2008, vol 11, p4022)) showed an important variability, with plasma levels distributed between less than 100 ng/ml and more than 4500 ng/ml. Sixty-two (22.3%) patients in our cohort had plasma levels below 647 ng/ml (Q1), 101(36.3%) patients had levels between 647–1170 ng/ml (Q2–Q3) and 115 (41.3%) patients had trough levels above 1170 ng/ml (Q4). There were 31 patients (11.2%) with levels above 2000 ng/ml, all of whom were included in the Q4. Thirty seven patients in our cohort had more than one analysis of trough imatinib plasma levels done during the one year follow-up for a total of 82 analyses. Sub-group analysis of trough imatinib plasma levels was conducted in the 13 patients in the Q1 and the six patients in the Q4 who had 2 analyses done. Mean trough imatinib plasma levels went from 401ng/ml to 665 ng/ml in the Q1 patients and from 2845 ng/ml to 1065 ng/ml in the Q4 patients. These results confirm the feasibility of imatinib plasma levels testing in the community and the important variability of trough imatinib plasma concentrations in individual patients, as described by other groups. A significant portion of patients in our cohort had trough levels below 647 ng/ml, which has been associated with less favourable cytogenetic and molecular responses in studies. These results also suggest that physicians act on the information procured by the determination of imatinib plasma levels as second level determination was improved for patients initially in Q1 or Q4. Further follow up analyses are needed to document if optimisation of dosing leads to better response or improvement in tolerability of the drug.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".