Yazarlar : Khoury HJ, Cortes JE, Kantarjian HM, et al

Yayın : Blood

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22371878

Konu : Lösemi

Literatür İçeriği :  

Abstract

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase I/II study evaluated the efficacy and safety of once-daily bosutinib 500 mg in patients with CML or acute lymphoblastic leukemia following 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 1 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 non-hematologic adverse events (>2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic phase CML following treatment with multiple TKIs.

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