Activity and tolerance of bosutinib in patients with AP and BP CML and Ph+ ALL

Abstract

7049 Background: Bosutinib (SKI-606) is an orally available, src/Abl kinase inhibitor with minimal activity against PDGFR and c-Kit. An open-label study in pts with Ph+ AP (Accelerated Phase) or BP (Blast Phase) CML and ALL (Acute Lymphoblastic Leukemia) who failed prior imatinib ± other TKI therapy, is currently ongoing. Methods: Pts with resistance or intolerance to imatinib (± other tyrosine kinase inhibitors) received 500 mg daily of bosutinib. Results: Data for 72 pts (32 AP CML, 23 BP CML and 17 Ph+ ALL) is reported. With a median follow-up of 6.1 wks, 18% achieved CHR and with a follow-up of 7.6 wks, 22% achieved a major cytogenetic response. 27/53 (51%) evaluable pts had 13 different Bcr/Abl mutations including 5 pts with T315I. Complete hematologic response occurred in 1/3 (33%) pts with P-loop, 2/15 (13%) with non-P-loop, and in 5/18 (28%) pts with no mutation. MCyR occurred in 1/2 (50%) of pts with P-loop, 3/12 (18%) with non-P-loop, and in 4/10 (40%) with no mutation. Only patients harboring T315I were consistently resistant to bosutinib. The most common treatment emergent adverse events (TEAEs) were diarrhea (61%), nausea (43%) and vomiting (38%); usually grade 1/2, manageable, and resolved after 3–4 weeks. Grade 3–4 hematologic laboratory abnormalities included thrombocytopenia (71%), neutropenia (46%) and anemia (32%). Fluid retention was reported as grade 1/2 in 11/72 (15%) and grade 3/4 in only 3/72 (4%) patients (including 2 pleural effusions). Fluid retention was considered unrelated to treatment in all cases. Conclusion: Bosutinib is active in pts with AP CML and BP CML and Ph+ ALL. Bosutinib demonstrates a favorable toxicity profile, primarily consisting of mild gastrointestinal symptoms. Response Patients Exposed to Imatinib Only Patients Exposed to Imatinib and other TKIs Patients, n (%) Patients, n (%) AP BP+ ALL AP BP +ALL Hematologic Response Evaluable 8 13 9 14 Complete 4 (50) 2 (15) 1 (11) 1 (7) Major (Complete + No evidence of leukemia) 7 (88) 2 (15) 1 (11) 1 (7) Cytogenetic Response Evaluable 9 11 6 10 Complete 2 (22) 1 (9) 0 2 (20) Major (Complete + Partial) 4 (44) 2 (18) 0 2 (20) Molecular Response Evaluable 8 14 7 15 Major 0 5 (36) 0 0 No significant financial relationships to disclose.