TY - JOUR
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.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
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.
AB - 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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M3 - Article
C2 - 12114418
AN - SCOPUS:0035992329
SN - 1078-0432
VL - 8
SP - 2177
EP - 2187
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -