Early Molecular Response Predicts Outcomes in Patients With Chronic Myeloid Leukemia in Chronic Phase Treated With Frontline Nilotinib or Imatinib

Blood. 2014 Feb 27;123(9):1353-60. doi: 10.1182/blood-2013-06-510396. Epub 2013 Dec 11.


We explored the impact of early molecular response (EMR; BCR-ABL ≤10% on the international scale [BCR-ABL(IS)] at 3 or 6 months) on outcomes in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with nilotinib or imatinib based on 4 years of follow up in Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients. Patients (n = 846) received nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, or imatinib 400 mg once daily. At 3 months, more patients had EMR failure (ie, BCR-ABL(IS) >10%) on imatinib (33%) than on nilotinib (9%-11%); similarly at 6 months, 16% of patients in the imatinib arm vs 3% and 7% in the nilotinib arms had EMR failure. In all arms, EMR failure was associated with lower rates of molecular response, an increased risk of progression, and lower overall survival compared with EMR achievement. We also analyzed patient and treatment characteristics associated with EMR and found distinct patterns in the nilotinib arms vs the imatinib arm. High Sokal risk score was associated with a high rate of EMR failure on imatinib, but not on nilotinib. In contrast, reduced dose intensity and dose interruptions were strongly associated with EMR failure in nilotinib-treated, but not imatinib-treated, patients. This study is registered at www.clinicaltrials.gov as #NCT00471497.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Benzamides / adverse effects
  • Benzamides / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Neoadjuvant Therapy
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Prognosis
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl

Associated data

  • ClinicalTrials.gov/NCT00471497