Imatinib mesylate (IM) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes so patient adherence is critical. There is a considerable variability in the level of molecular responses achieved with IM therapy. These differences could result from variable drug levels which may be due to adherence factor or other factors. This study was designed to determine the relation between drug adherence, imatinib plasma level and clinical response.
This study was designed as a prospective, observational, non-interventional study. A total of 101 patients with chronic-phase CML treated with IM were enrolled. The study protocol was approved by the Institutional Review Board of the National Cancer Institute of Cairo University, Egypt. Adherence was monitored by using Morisky medication adherence scores (MMAS). Drug level was measured as peak and trough concentration after reaching steady state using high performance liquid chromatography mass spectroscopy (HPLC/MS) and peak/ trough ratio (P/T ratio) was calculated.
The mean IM trough plasma level in patients who achieved unfavorable response (n = 37) was 1183.92 ng/ml, and in patients who achieved favorable response (n = 64) 1560.16 ng/ml (p = 0.006). The P/T ratio in patients who achieved unfavorable response was 3.03 and in patients who achieved favorable response 2.06 (p = 0.001). There was no significant correlation between adherence score and clinical response. Multivariate analysis identified P/T ratio as the only independent predictors of clinical response.
In patients with CML treated with IM the significant independent factor affecting response was P/T ratio. As the peak/trough ratio increase by one, the risk of poor response increased by more than double compared with a good response with 95% CI:1.28 – 3.92 (P = 0.005).
Clinical trial identification
Legal entity responsible for the study
National Cancer Institute
National Cancer Institute, Cairo University
All authors have declared no conflicts of interest.