Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase

Yesid Alvarado, Hagop Kantarjian, Susan O'Brien, Stefan Faderl, Gautam Borthakur, Jan Burger, William Wierda, Guillermo Garcia-Manero, Jianqin Shan, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined. METHODS: The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard-dose (n = 73) or high-dose (n = 208) imatinib was investigated. RESULTS: Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event-free survival (EFS) and transformation-free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose. CONCLUSIONS: The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required.

Original languageEnglish (US)
Pages (from-to)3709-3718
Number of pages10
JournalCancer
Volume115
Issue number16
DOIs
StatePublished - Aug 15 2009
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease-Free Survival
Survival
Imatinib Mesylate
Cytogenetics
Multivariate Analysis
Therapeutics

Keywords

  • Chronic myeloid leukemia
  • Chronic phase
  • Imatinib
  • Suboptimal response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase. / Alvarado, Yesid; Kantarjian, Hagop; O'Brien, Susan; Faderl, Stefan; Borthakur, Gautam; Burger, Jan; Wierda, William; Garcia-Manero, Guillermo; Shan, Jianqin; Cortes, Jorge.

In: Cancer, Vol. 115, No. 16, 15.08.2009, p. 3709-3718.

Research output: Contribution to journalArticle

Alvarado, Y, Kantarjian, H, O'Brien, S, Faderl, S, Borthakur, G, Burger, J, Wierda, W, Garcia-Manero, G, Shan, J & Cortes, J 2009, 'Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase', Cancer, vol. 115, no. 16, pp. 3709-3718. https://doi.org/10.1002/cncr.24418
Alvarado, Yesid ; Kantarjian, Hagop ; O'Brien, Susan ; Faderl, Stefan ; Borthakur, Gautam ; Burger, Jan ; Wierda, William ; Garcia-Manero, Guillermo ; Shan, Jianqin ; Cortes, Jorge. / Significance of suboptimal response to imatinib, as defined by the European LeukemiaNet, in the long-term outcome of patients with early chronic myeloid leukemia in chronic phase. In: Cancer. 2009 ; Vol. 115, No. 16. pp. 3709-3718.
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AU - O'Brien, Susan

AU - Faderl, Stefan

AU - Borthakur, Gautam

AU - Burger, Jan

AU - Wierda, William

AU - Garcia-Manero, Guillermo

AU - Shan, Jianqin

AU - Cortes, Jorge

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N2 - BACKGROUND: The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined. METHODS: The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard-dose (n = 73) or high-dose (n = 208) imatinib was investigated. RESULTS: Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event-free survival (EFS) and transformation-free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose. CONCLUSIONS: The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required.

AB - BACKGROUND: The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined. METHODS: The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard-dose (n = 73) or high-dose (n = 208) imatinib was investigated. RESULTS: Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event-free survival (EFS) and transformation-free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose. CONCLUSIONS: The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required.

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