Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α: Follow-up results

Hagop 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 AlbitarEmil J. Freireich, Jorge E. Cortes

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

Abstract

We treated 261 patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase after failure of IFN-α 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-α 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-α 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-α failure. We identified pretreatment and treatment-associated factors that were associated with higher major cytogenetic response rates and with improved survival.

Original languageEnglish (US)
Pages (from-to)2177-2187
Number of pages11
JournalClinical Cancer Research
Volume8
Issue number7
StatePublished - 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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