6591 Background: AMN107 is a novel, highly selective oral Bcr-Abl inhibitor which is 20–50-fold more potent than imatinib. High response rates with AMN107 were observed in all CML phases post imatinib failure. Methods: Study Aims: Evaluate the efficacy of AMN107in newly diagnosed Ph-positive CML-CP. Study Group and Therapy: Patients with newly diagnosed Ph-positive CML-CP were treated with AMN107 400 mg orally twice daily. Results: So far, 13 patients have been treated; median age 49 (range 24 to 72). Sokal risk at pretreatment: low - 10, intermediate - 2, high - 1. Five have reached the 3 month evaluation: all 5 (100%) had a complete cytogenetic response [CGCR] (Ph 0%). This is compared with a CGCR at 3 months of 36% with imatinib 400 mg/d and 55% with imatinib 800 mg/d in historical data of newly diagnosed patients treated at M. D. Anderson. The median QPCR with AMN at 3 months was 0.67% (range 0.3 to 3.0), compared with a median QPCR of 8% with imatinib 800 mg daily. Grade 3–4 myelosuppression was observed in 3/13 and other grade 3–4 side effects in 1/13 requiring temporary AMN107 interruption for < 2 weeks and resumption at same dose level in the 3 patients with myelosuppression, and for 6 weeks+ in the patient with grade 3 elevation of liver enzymes which were reduced to grade 1 on last follow-up. One patient had a transient elevation of total bilirubin > 3 mg/L which was self limited with continued therapy. Conclusions: Early results with AMN107 400 mg orally twice daily are encouraging in newly diagnosed CML. [Table: see text]