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

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213 Scopus citations

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
Publication statusPublished - Apr 12 2012
Externally publishedYes

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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