Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia: What is the optimal response?

Elias Jabbour, Hagop M. Kantarjian, Susan O'Brien, Jianqin Shan, Alfonso Quintás-Cardama, Guillermo Garcia-Manero, Mary Beth Rios, Jorge E. Cortes

Research output: Contribution to journalArticle

Abstract

Purpose: The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs). Patients and Methods: One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time. Results: Overall, 155 patients (93%) achieved complete cytogenetic response (CCyR), including 146 (87%) with major molecular response (MMR; complete in 46 patients [28%]). According to the ELN definitions, the rates of suboptimal response were 0%, 2%, 1%, and 12% at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months. Conclusion: The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.

Original languageEnglish (US)
Pages (from-to)4260-4265
Number of pages6
JournalJournal of Clinical Oncology
Volume29
Issue number32
DOIs
StatePublished - Nov 10 2011
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Cytogenetics
Protein-Tyrosine Kinases
Therapeutics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease-Free Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia : What is the optimal response? / Jabbour, Elias; Kantarjian, Hagop M.; O'Brien, Susan; Shan, Jianqin; Quintás-Cardama, Alfonso; Garcia-Manero, Guillermo; Rios, Mary Beth; Cortes, Jorge E.

In: Journal of Clinical Oncology, Vol. 29, No. 32, 10.11.2011, p. 4260-4265.

Research output: Contribution to journalArticle

Jabbour, Elias ; Kantarjian, Hagop M. ; O'Brien, Susan ; Shan, Jianqin ; Quintás-Cardama, Alfonso ; Garcia-Manero, Guillermo ; Rios, Mary Beth ; Cortes, Jorge E. / Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia : What is the optimal response?. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 32. pp. 4260-4265.
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title = "Front-line therapy with second-generation tyrosine kinase inhibitors in patients with early chronic phase chronic myeloid leukemia: What is the optimal response?",
abstract = "Purpose: The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs). Patients and Methods: One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time. Results: Overall, 155 patients (93{\%}) achieved complete cytogenetic response (CCyR), including 146 (87{\%}) with major molecular response (MMR; complete in 46 patients [28{\%}]). According to the ELN definitions, the rates of suboptimal response were 0{\%}, 2{\%}, 1{\%}, and 12{\%} at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months. Conclusion: The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.",
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AU - Jabbour, Elias

AU - Kantarjian, Hagop M.

AU - O'Brien, Susan

AU - Shan, Jianqin

AU - Quintás-Cardama, Alfonso

AU - Garcia-Manero, Guillermo

AU - Rios, Mary Beth

AU - Cortes, Jorge E.

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N2 - Purpose: The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs). Patients and Methods: One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time. Results: Overall, 155 patients (93%) achieved complete cytogenetic response (CCyR), including 146 (87%) with major molecular response (MMR; complete in 46 patients [28%]). According to the ELN definitions, the rates of suboptimal response were 0%, 2%, 1%, and 12% at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months. Conclusion: The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.

AB - Purpose: The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs). Patients and Methods: One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time. Results: Overall, 155 patients (93%) achieved complete cytogenetic response (CCyR), including 146 (87%) with major molecular response (MMR; complete in 46 patients [28%]). According to the ELN definitions, the rates of suboptimal response were 0%, 2%, 1%, and 12% at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months. Conclusion: The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.

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