6501 Background: Study results of ENESTnd at 12 month (mo) demonstrated superior efficacy of nilotinib 300 and 400 mg bid over imatinib. Methods: 846 CML-CP pts were randomized to nilotinib 300 mg bid (n=282), nilotinib 400 mg bid (n=281), and imatinib 400 mg qd (n=283). Primary endpoint was major molecular response (MMR, ≤ 0.1% BCR-ABLIS) rate at 12 mo. Results: Rates of MMR and CCyR were superior for nilotinib 300 and 400 mg bid compared with imatinib and deeper molecular responses were also achieved with nilotinib at both doses (Table). Suboptimal responses and treatment failure (based on cytogenetic criteria) were less frequent on the nilotinib arms. Progression to advanced disease was lower for nilotinib at both doses compared with imatinib (Table); no pt who achieved MMR progressed; 3 pts who achieved CCyR on imatinib progressed. There were no unexpected safety events. Discontinuations due to adverse events or abnormal laboratory values were lowest for nilotinib 300 mg bid (7%). Overall, 1% of pts discontinued nilotinib due to hepatobilliary disorders; only 1 pt discontinued due to pancreatitis and 1 pt due to ischemic heart disease. Pleural effusions (any grade) occurred in <1% of nilotinib treated pts. Minimum 16 mo follow-up data will be presented (maximum, 29 mo). Conclusions: Nilotinib induced twice the MMR rate compared with imatinib and resulted in significantly lower rates of transformation to advanced disease, which support the potential of nilotinib to become the new standard of care in newly diagnosed CML. Nilotinib 300 mg bid (N = 282) Nilotinib 400 mg bid (N = 281) Imatinib 400 mg qd (N = 283) MMR, % At 12 mo 44*P < 0.0001 43* P < 0.0001 22 High-risk Sokal (12 mo) 41 32 17 Best molecular response with current follow-up, % ≤ 0.1% IS (MMR) 57 54 30 ≤ 0.01% IS 24 21 10 ≤ 0.0032% IS 13 12 4 CCyR, % By 12 mo 80* p < 0.0001 78* p = 0.0005 65 High-risk Sokal (12 mo) 74 63 49 Suboptimal response, % 5 5 13 Treatment failure, % 1 2 8 Progression to AP/BC, % Estimated rate at 12 mo 0.7 p = 0.0095** 0.4 p = 0.0037** 3.5 Above, including clonal evolution 0.7 p = 0.0006** 1.4 p = 0.0025** 4.8 * CMH test stratified by Sokal vs. imatinib. ** Log-rank test stratified by Sokal vs. imatinib for time to AP/BC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, MSD, Novartis Novartis Bristol-Myers Squibb, Celgene, MSD, Novartis Bristol-Myers Squibb, Genzyme, Novartis