Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib

J Clin Oncol. 2010 May 10;28(14):2381-8. doi: 10.1200/JCO.2009.26.3087. Epub 2010 Apr 12.

Abstract

Purpose: There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence.

Methods: Eighty-seven patients with chronic-phase CML treated with imatinib 400 mg/d for a median of 59.7 months (range, 25 to 104 months) who had achieved complete cytogenetic response had adherence monitored during a 3-month period by using a microelectronic monitoring device. Adherence was correlated with levels of molecular response. Other factors that could influence outcome were also analyzed.

Results: Median adherence rate was 98% (range, 24% to 104%). Twenty-three patients (26.4%) had adherence <or= 90%; in 12 of these patients (14%), adherence was <or= 80%. There was a strong correlation between adherence rate (<or= 90% or > 90%) and the 6-year probability of a 3-log reduction (also known as major molecular response [MMR]) in BCR-ABL1 transcripts (28.4% v 94.5%; P < .001) and also complete molecular response (CMR; 0% v 43.8%; P = .002). Multivariate analysis identified adherence (relative risk [RR], 11.7; P = .001) and expression of the molecular human organic cation transporter-1 (RR, 1.79; P = .038) as the only independent predictors for MMR. Adherence was the only independent predictor for CMR. No molecular responses were observed when adherence was <or= 80% (P < .001). Patients whose imatinib doses were increased had poor adherence (86.4%). In this latter population, adherence was the only independent predictor for inability to achieve an MMR (RR, 17.66; P = .006).

Conclusion: In patients with CML treated with imatinib for some years, poor adherence may be the predominant reason for inability to obtain adequate molecular responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Cytogenetic Analysis*
  • Drug Monitoring / instrumentation
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Imatinib Mesylate
  • Kaplan-Meier Estimate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Logistic Models
  • Male
  • Medication Adherence*
  • Micro-Electrical-Mechanical Systems / instrumentation
  • Middle Aged
  • Mutation
  • Octamer Transcription Factor-1 / genetics
  • Piperazines / pharmacokinetics
  • Piperazines / therapeutic use*
  • Polymorphism, Genetic
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / therapeutic use*
  • RNA, Messenger / metabolism
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Benzamides
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Messenger
  • abl-bcr fusion protein, human
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl