Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy

Hagop Kantarjian, Susan O'Brien, Guillermo Garcia-Manero, Stefan Faderl, Farhad Ravandi, Elias Jabbour, Jianqin Shan, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed. METHODS: In total, 368 patients were analyzed. Univariate and multivariate survival analyses were conducted using standard statistical methods. RESULTS: Overall, 247 patients (67%) achieved a complete cytogenetic response (CCyR). Of the 327 patients who were studied, 207 patients (63%) achieved a major molecular response (MMR), and 99 patients (30%) had undetectable breakpoint cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The estimated 10-year survival rate was 68%, the progression-free survival rate was 67%, and the event-free survival rate was 51%. In multivariate analysis, age ≥60 years, hemoglobin <10 g/dL, bone marrow basophils ≥5%, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The estimated 7-year survival rate according to the presence of no factors (n = 154), 1 or 2 factors (n = 190), or ≥3 factors (n = 24) were 93%, 70%, and 25%, respectively (P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic response at 12 months was associated with significantly better 10-year survival rate in a landmark analysis (10-year survival rate, 80%-90%) compared with achieving a minor cytogenetic response or a complete hematologic response (10-year survival rate, 55%-65%) or another response (10-year survival rate, 10%). In a landmark analysis that included imatinib response at 12 months, achieving a major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving a complete hematologic response or a minor cytogenetic response (hazard ratio, 0.36; P = .003) were significant favorable prognostic factors. CONCLUSIONS: The current results indicated that the estimated 10-year survival rate of 68% for patients with chronic myeloid leukemia who receive imatinib after failure on interferon has improved.

Original languageEnglish (US)
Pages (from-to)3116-3122
Number of pages7
JournalCancer
Volume118
Issue number12
DOIs
StatePublished - Jun 15 2012
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Interferon-alpha
Survival Rate
Cytogenetics
Therapeutics
Disease-Free Survival
Multivariate Analysis
abl Genes
Clonal Evolution
Imatinib Mesylate
Basophils
Survival Analysis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferons
Hemoglobins
Bone Marrow

Keywords

  • Chronic myeloid leukemia
  • Chronic phase
  • Failure
  • Imatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy. / Kantarjian, Hagop; O'Brien, Susan; Garcia-Manero, Guillermo; Faderl, Stefan; Ravandi, Farhad; Jabbour, Elias; Shan, Jianqin; Cortes, Jorge.

In: Cancer, Vol. 118, No. 12, 15.06.2012, p. 3116-3122.

Research output: Contribution to journalArticle

Kantarjian, H, O'Brien, S, Garcia-Manero, G, Faderl, S, Ravandi, F, Jabbour, E, Shan, J & Cortes, J 2012, 'Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy', Cancer, vol. 118, no. 12, pp. 3116-3122. https://doi.org/10.1002/cncr.26568
Kantarjian, Hagop ; O'Brien, Susan ; Garcia-Manero, Guillermo ; Faderl, Stefan ; Ravandi, Farhad ; Jabbour, Elias ; Shan, Jianqin ; Cortes, Jorge. / Very long-term follow-up results of imatinib mesylate therapy in chronic phase chronic myeloid leukemia after failure of interferon alpha therapy. In: Cancer. 2012 ; Vol. 118, No. 12. pp. 3116-3122.
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abstract = "BACKGROUND: The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed. METHODS: In total, 368 patients were analyzed. Univariate and multivariate survival analyses were conducted using standard statistical methods. RESULTS: Overall, 247 patients (67{\%}) achieved a complete cytogenetic response (CCyR). Of the 327 patients who were studied, 207 patients (63{\%}) achieved a major molecular response (MMR), and 99 patients (30{\%}) had undetectable breakpoint cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The estimated 10-year survival rate was 68{\%}, the progression-free survival rate was 67{\%}, and the event-free survival rate was 51{\%}. In multivariate analysis, age ≥60 years, hemoglobin <10 g/dL, bone marrow basophils ≥5{\%}, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The estimated 7-year survival rate according to the presence of no factors (n = 154), 1 or 2 factors (n = 190), or ≥3 factors (n = 24) were 93{\%}, 70{\%}, and 25{\%}, respectively (P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic response at 12 months was associated with significantly better 10-year survival rate in a landmark analysis (10-year survival rate, 80{\%}-90{\%}) compared with achieving a minor cytogenetic response or a complete hematologic response (10-year survival rate, 55{\%}-65{\%}) or another response (10-year survival rate, 10{\%}). In a landmark analysis that included imatinib response at 12 months, achieving a major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving a complete hematologic response or a minor cytogenetic response (hazard ratio, 0.36; P = .003) were significant favorable prognostic factors. CONCLUSIONS: The current results indicated that the estimated 10-year survival rate of 68{\%} for patients with chronic myeloid leukemia who receive imatinib after failure on interferon has improved.",
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AU - Faderl, Stefan

AU - Ravandi, Farhad

AU - Jabbour, Elias

AU - Shan, Jianqin

AU - Cortes, Jorge

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N2 - BACKGROUND: The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed. METHODS: In total, 368 patients were analyzed. Univariate and multivariate survival analyses were conducted using standard statistical methods. RESULTS: Overall, 247 patients (67%) achieved a complete cytogenetic response (CCyR). Of the 327 patients who were studied, 207 patients (63%) achieved a major molecular response (MMR), and 99 patients (30%) had undetectable breakpoint cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The estimated 10-year survival rate was 68%, the progression-free survival rate was 67%, and the event-free survival rate was 51%. In multivariate analysis, age ≥60 years, hemoglobin <10 g/dL, bone marrow basophils ≥5%, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The estimated 7-year survival rate according to the presence of no factors (n = 154), 1 or 2 factors (n = 190), or ≥3 factors (n = 24) were 93%, 70%, and 25%, respectively (P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic response at 12 months was associated with significantly better 10-year survival rate in a landmark analysis (10-year survival rate, 80%-90%) compared with achieving a minor cytogenetic response or a complete hematologic response (10-year survival rate, 55%-65%) or another response (10-year survival rate, 10%). In a landmark analysis that included imatinib response at 12 months, achieving a major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving a complete hematologic response or a minor cytogenetic response (hazard ratio, 0.36; P = .003) were significant favorable prognostic factors. CONCLUSIONS: The current results indicated that the estimated 10-year survival rate of 68% for patients with chronic myeloid leukemia who receive imatinib after failure on interferon has improved.

AB - BACKGROUND: The long-term outcome of patients with chronic phase chronic myeloid leukemia treated with imatinib after failure of interferon alpha therapy has not been detailed. METHODS: In total, 368 patients were analyzed. Univariate and multivariate survival analyses were conducted using standard statistical methods. RESULTS: Overall, 247 patients (67%) achieved a complete cytogenetic response (CCyR). Of the 327 patients who were studied, 207 patients (63%) achieved a major molecular response (MMR), and 99 patients (30%) had undetectable breakpoint cluster region/c-abl oncogene (BCR-ABL) levels at some time during therapy. The estimated 10-year survival rate was 68%, the progression-free survival rate was 67%, and the event-free survival rate was 51%. In multivariate analysis, age ≥60 years, hemoglobin <10 g/dL, bone marrow basophils ≥5%, any peripheral blasts, and clonal evolution were independent adverse factors for survival. The estimated 7-year survival rate according to the presence of no factors (n = 154), 1 or 2 factors (n = 190), or ≥3 factors (n = 24) were 93%, 70%, and 25%, respectively (P < .01). Achieving an MMR, a CCyR, or a partial cytogenetic response at 12 months was associated with significantly better 10-year survival rate in a landmark analysis (10-year survival rate, 80%-90%) compared with achieving a minor cytogenetic response or a complete hematologic response (10-year survival rate, 55%-65%) or another response (10-year survival rate, 10%). In a landmark analysis that included imatinib response at 12 months, achieving a major cytogenetic response or better (hazard ratio, 0.12; P < .001) and achieving a complete hematologic response or a minor cytogenetic response (hazard ratio, 0.36; P = .003) were significant favorable prognostic factors. CONCLUSIONS: The current results indicated that the estimated 10-year survival rate of 68% for patients with chronic myeloid leukemia who receive imatinib after failure on interferon has improved.

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