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

Research output: Contribution to journalArticle

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 - Jul 22 2002
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Cytogenetics
Interferons
Survival
Bone Marrow
bcr-abl Fusion Proteins
Survival Rate
Clonal Evolution
Imatinib Mesylate
Leukocytosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cell- and Tissue-Based Therapy
Multivariate Analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α : Follow-up results. / Kantarjian, Hagop M.; Talpaz, Moshe; O'Brien, Susan; Smith, Terry L.; Giles, Francis J.; Faderl, Stefan; Thomas, Deborah A.; Garcia-Manero, Guillermo; Issa, Jean Pierre J.; Andreeff, Michael; Kornblau, Steven M.; Koller, Charles; Beran, Milosav; Keating, Michael; Rios, Mary Beth; Shan, Jenny; Resta, Debra; Capdeville, Renaud; Hayes, Kimberly; Albitar, Maher; Freireich, Emil J.; Cortes, Jorge E.

In: Clinical Cancer Research, Vol. 8, No. 7, 22.07.2002, p. 2177-2187.

Research output: Contribution to journalArticle

Kantarjian, HM, Talpaz, M, O'Brien, S, Smith, TL, Giles, FJ, Faderl, S, Thomas, DA, Garcia-Manero, G, Issa, JPJ, Andreeff, M, Kornblau, SM, Koller, C, Beran, M, Keating, M, Rios, MB, Shan, J, Resta, D, Capdeville, R, Hayes, K, Albitar, M, Freireich, EJ & Cortes, JE 2002, 'Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α: Follow-up results', Clinical Cancer Research, vol. 8, no. 7, pp. 2177-2187.
Kantarjian, Hagop M. ; Talpaz, Moshe ; O'Brien, Susan ; Smith, Terry L. ; Giles, Francis J. ; Faderl, Stefan ; Thomas, Deborah A. ; Garcia-Manero, Guillermo ; Issa, Jean Pierre J. ; Andreeff, Michael ; Kornblau, Steven M. ; Koller, Charles ; Beran, Milosav ; Keating, Michael ; Rios, Mary Beth ; Shan, Jenny ; Resta, Debra ; Capdeville, Renaud ; Hayes, Kimberly ; Albitar, Maher ; Freireich, Emil J. ; Cortes, Jorge E. / Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α : Follow-up results. In: Clinical Cancer Research. 2002 ; Vol. 8, No. 7. pp. 2177-2187.
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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.",
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T1 - Imatinib mesylate for Philadelphia chromosome-positive, chronic-phase myeloid leukemia after failure of interferon-α

T2 - Follow-up results

AU - Kantarjian, Hagop M.

AU - Talpaz, Moshe

AU - O'Brien, Susan

AU - Smith, Terry L.

AU - Giles, Francis J.

AU - Faderl, Stefan

AU - Thomas, Deborah A.

AU - Garcia-Manero, Guillermo

AU - Issa, Jean Pierre J.

AU - Andreeff, Michael

AU - Kornblau, Steven M.

AU - Koller, Charles

AU - Beran, Milosav

AU - Keating, Michael

AU - Rios, Mary Beth

AU - Shan, Jenny

AU - Resta, Debra

AU - Capdeville, Renaud

AU - Hayes, Kimberly

AU - Albitar, Maher

AU - Freireich, Emil J.

AU - Cortes, Jorge E.

PY - 2002/7/22

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N2 - 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.

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