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

Mené sur 118 patients atteints d'une leucémie myéloïde chronique en phase chronique, cet essai de phase I/II évalue la toxicité et l'efficacité du bosutinib après l'échec d'un traitement à l'imatinib, puis au dasatinib et/ou au nilotinib

• Blood, sous presse, 2012 (résumé)

Résumé en anglais :
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.

NBC n° 126 du 06 Mars 2012

Mots clés : Leucémie; Traitements (Traitements systémiques : découverte et développement)