Efficacy And Safety Of Nilotinib 800 Mg Daily In Early Chronic Phase Ph Plus Chronic Myeloid Leukemia: Results Of A Phase Ii Trial At 2 Years.

6515 Background: Imatinib (IM) 400 mg daily is the standard treatment for Ph+ CML in early chronic phase (ECP). One-fourth of all the IM treated pts fail to obtain a stable complete cytogenetic response (CCgR) due to upfront resistance, refractoriness or intolerance. Nilotinib is highly effective in IM resistant and intolerant patients. To investigate the safety and efficacy of nilotinib 400 mg BID in ECP, Ph- pos CML patients, the GIMEMA CML Working Party is conducting a multicentric phase II trial (ClinicalTrials.gov.NCT00481052). Methods: The primary endpoint is the CCgR rate at 1 year; the molecular response is studied serially by Q-PCR (major molecular response, MMR, ≤ 0.1% according to the International Scale). By March, 2010 all the patients will complete 24 months on treatment. Results: 73 patients have been enrolled, median age 51 years (range 18-83), 45% low, 41% intermediate and 14% high Sokal risk. Median follow-up is currently 724 days (range 447-833). The cumulative CCgR rate within 12 months is 100%. At 3, 6 and 12 months (ITT), the CCgR rate is 78% at 3 months and 96% at 6,12 and 18 months. The rates of MMR, at 1, 2, 3, 6, 12, and 18 months are 3%, 21%, 52%, 66%, 85% and 87%, respectively. One patient only progressed at 6 months to advanced phase (ABP) with T315I mutation. The nilotinib dose intensity was high: during the first quarter, the second quarter and the second half, 82%, 75% and 71% of patients, respectively, received ≥ 600 mg daily. Adverse events (AEs) were mostly grade 1 and 2 and manageable with appropriate dose adaptations: the most frequent biochemical AEs were bilirubin increase (53% all grades, 16% grade 3), s-GPT increase (42% all grades, 8% grade 3) and lipase and amylase increase (29% and 18%, all grades, 8% and 4% grade 3+4, respectively); 2 pts went off treatment after 9 and 15 months due to recurrent episodes of amylase and/or lipase increase (no pancreatitis). Conclusions: After 2 years, responses to nilotinib, either CCgR and MMR, are stable. No progressions to ABP have been observed during the second year. These results strongly support the use of nilotinib as first-line treatment in ECP CML. Acknowledgements: European LeukemiaNet, COFIN, Bologna University, BolognAIL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis, Wyeth Bristol-Myers Squibb, Novartis, Wyeth Bristol-Myers Squibb, Novartis, Wyeth