A phase II study of nilotinib administered to patients with imatinib resistant or intolerant chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated phase (AP) or blast crisis (BC) who also failed dasatinib

Abstract

7038 Background: Nilotinib and dasatinib are two new second generation tyrosine kinase inhibitors used in the treatment of imatinib-resistant/intolerant CML. There is limited data regarding the efficacy and safety of these therapies when given sequentially. Methods: This phase II open-label study was designed to evaluate the safety and efficacy of nilotinib at a dose of 400mg BID in CML-CP, -AP, and -BC pts who previously received and either failed or were intolerant to imatinib and dasatinib. Results: A total of 42 pts are reported - CP (16), AP (9), and BC (17 total; 13 myeloid, 4 lymphoid). Overall 10 (24%) pts had extramedullary disease at baseline. For all pts, median time from first diagnosis was 16.8 (0.6–265) months. The median duration of nilotinib exposure was 81 days with median dose intensity of 800mg/day. A total of 13 (31%) pts with dasatinib failure remain on treatment, 29 (69%) discontinued (6 for AEs, 16 for disease progression). CP: Of the 16 pts, 5 (31%) had a MCyR (3 complete, 2 partial). Complete hematologic response (CHR) was reported in 5/13 (39%) pts without CHR at baseline. Disease progression only occurred in 2 pts. AP: 2/9 (22%) pts had a return to chronic phase (RTC), 6 pts were not evaluable and there was 1 death. Disease progression occurred in 5 pts. BC: 3/17 (18%) achieved CHR, 1 (6%) had RTC, and 4 (24%) pts had disease progression. For all pts, the most common Grade 3/4 AEs reported were thrombocytopenia (26%), neutropenia (24%), and anemia (7%) pts. Conclusions: Nilotinib has significant clinical activity in CML-CP, AP, and BC patients who have failed imatinib and dasatinib. Nilotinib is safe and well tolerated, consistent with its kinase selectivity profile. No significant financial relationships to disclose.