Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase

Leukemia. 2003 Dec;17(12):2401-9. doi: 10.1038/sj.leu.2403158.


We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%, which significantly exceeded those of IFN+AraC-treated patients and early measurements were predictive of subsequent response.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antineoplastic Agents / administration & dosage*
  • Benzamides
  • Bone Marrow / metabolism
  • Cross-Over Studies
  • Cytarabine / administration & dosage*
  • Cytogenetics
  • DNA Mutational Analysis
  • Fusion Proteins, bcr-abl / blood
  • Fusion Proteins, bcr-abl / chemistry
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • Interferon-alpha / administration & dosage*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Phosphotransferases / chemistry
  • Phosphotransferases / genetics
  • Piperazines / administration & dosage*
  • Prognosis
  • Protein Structure, Tertiary
  • Pyrimidines / administration & dosage*
  • Treatment Outcome


  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Benzamides
  • Interferon-alpha
  • Piperazines
  • Pyrimidines
  • Cytarabine
  • Imatinib Mesylate
  • Phosphotransferases
  • Fusion Proteins, bcr-abl