Correlation between imatinib pharmacokinetics and clinical response in Japanese patients with chronic-phase chronic myeloid leukemia

Clin Pharmacol Ther. 2010 Dec;88(6):809-13. doi: 10.1038/clpt.2010.186. Epub 2010 Oct 27.

Abstract

Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-C(min)) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-C(min) was 1,010.5 ng/ml. Importantly, IM-C(min) was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (OR) = 0.97 (0.958-0.995); P = 0.0153) and with IM-C(min) (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-C(min) values >1,002 ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People*
  • Benzamides
  • Cohort Studies
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / metabolism*
  • Male
  • Middle Aged
  • Piperazines / pharmacokinetics*
  • Piperazines / therapeutic use*
  • Pyrimidines / pharmacokinetics*
  • Pyrimidines / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate