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Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-alpha: follow-up results.

Abstract
We treated 261 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase after failure of IFN-alpha with the Bcr-Abl tyrosine kinase inhibitor imatinib mesylate (400 mg/day given p.o.) and analyzed hematological and cytogenetic responses, long-term prognosis, factors associated with achievement of major cytogenetic response and survival, and comparative survival in similar patients treated with other regimens. Median patient age was 55 years; 34% were 60 years or older, and median chronic-phase duration was 33 months. Overall, 94% achieved a complete hematological response, and 71% had a cytogenetic response [major (Ph+ cells <35%) in 62% and complete in 45%]. At a median follow-up of 17 months, 241 patients (92%) were still taking imatinib mesylate; estimated 18-month freedom from progression and survival rates were 93 and 96%. Multivariate analysis of factors associated with major cytogenetic response identified long chronic phase, marrow basophilia, high percentage of Ph+ cells before therapy, and prior hematological resistance to IFN-alpha as being adverse factors. This model was used to generate good-, intermediate- and poor-risk subgroups who had estimated major cytogenetic response rates of 93, 53, and 34%, respectively. Univariate analysis in terms of survival identified leukocytosis, high percentages of peripheral and marrow blasts, marrow basophilia, and the presence of cytogenetic clonal evolution as being adverse factors. Achieving a cytogenetic response at 3 or 6 months of therapy was associated with prolonged survival. In a subset analysis, survival rates among 161 patients with Ph-positive CML after hematological or cytogenetic failure after IFN-alpha who had been treated with imatinib mesylate were better than those for similar patients treated previously with other regimens. In summary, imatinib mesylate is highly effective in chronic-phase CML after IFN-alpha failure. We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival.
AuthorsHagop M Kantarjian, Moshe Talpaz, Susan O'Brien, Terry L Smith, Francis J Giles, Stefan Faderl, Deborah A Thomas, Guillermo Garcia-Manero, Jean-Pierre J Issa, Michael Andreeff, Steven M Kornblau, Charles Koller, Milosav Beran, Michael Keating, Mary Beth Rios, Jenny Shan, Debra Resta, Renaud Capdeville, Kimberly Hayes, Maher Albitar, Emil J Freireich, Jorge E Cortes
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 8 Issue 7 Pg. 2177-87 (Jul 2002) ISSN: 1078-0432 [Print] United States
PMID12114418 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzamides
  • Enzyme Inhibitors
  • Interferon-alpha
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
Topics
  • Benzamides
  • Chronic Disease
  • Cytogenetic Analysis
  • Enzyme Inhibitors (therapeutic use)
  • Female
  • Follow-Up Studies
  • Humans
  • Imatinib Mesylate
  • Interferon-alpha (therapeutic use)
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, mortality, pathology)
  • Male
  • Middle Aged
  • Piperazines (therapeutic use)
  • Prognosis
  • Protein-Tyrosine Kinases (antagonists & inhibitors)
  • Pyrimidines (therapeutic use)
  • Survival Rate
  • Treatment Failure
  • Treatment Outcome

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