Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure

H. Jean Khoury, Jorge E. Cortes, Hagop M. Kantarjian, Carlo Gambacorti-Passerini, Michele Baccarani, Dong Wook Kim, Andrey Zaritskey, Athena Countouriotis, Nadine Besson, Eric Leip, Virginia Kelly, Tim H. Brümmendorf

Research output: Contribution to journalArticle

Abstract

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier- estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

Original languageEnglish (US)
Pages (from-to)3403-3412
Number of pages10
JournalBlood
Volume119
Issue number15
DOIs
StatePublished - Apr 12 2012

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Leukemia, Myeloid, Chronic Phase
Therapeutics
Exanthema
Cytogenetics
Protein-Tyrosine Kinases
Blast Crisis
Safety
src-Family Kinases
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Dasatinib
bosutinib
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Disease-Free Survival
Diarrhea
Leukemia
Mutation
Survival

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Khoury, H. J., Cortes, J. E., Kantarjian, H. M., Gambacorti-Passerini, C., Baccarani, M., Kim, D. W., ... Brümmendorf, T. H. (2012). Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood, 119(15), 3403-3412. https://doi.org/10.1182/blood-2011-11-390120

Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. / Khoury, H. Jean; Cortes, Jorge E.; Kantarjian, Hagop M.; Gambacorti-Passerini, Carlo; Baccarani, Michele; Kim, Dong Wook; Zaritskey, Andrey; Countouriotis, Athena; Besson, Nadine; Leip, Eric; Kelly, Virginia; Brümmendorf, Tim H.

In: Blood, Vol. 119, No. 15, 12.04.2012, p. 3403-3412.

Research output: Contribution to journalArticle

Khoury, HJ, Cortes, JE, Kantarjian, HM, Gambacorti-Passerini, C, Baccarani, M, Kim, DW, Zaritskey, A, Countouriotis, A, Besson, N, Leip, E, Kelly, V & Brümmendorf, TH 2012, 'Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure', Blood, vol. 119, no. 15, pp. 3403-3412. https://doi.org/10.1182/blood-2011-11-390120
Khoury, H. Jean ; Cortes, Jorge E. ; Kantarjian, Hagop M. ; Gambacorti-Passerini, Carlo ; Baccarani, Michele ; Kim, Dong Wook ; Zaritskey, Andrey ; Countouriotis, Athena ; Besson, Nadine ; Leip, Eric ; Kelly, Virginia ; Brümmendorf, Tim H. / Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. In: Blood. 2012 ; Vol. 119, No. 15. pp. 3403-3412.
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AU - Kim, Dong Wook

AU - Zaritskey, Andrey

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