TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets

Yeung, D.Osborn, M.White, D.Branford, S.Braley, J.Herschtal, A.Kornhauser, M.Issa, S.Hiwase, D.Hertzberg, M.Schwarer, A.Filshie, R.Arthur, C.Kwan, Y.Trotman, J.Forsyth, C.Taper, J.Ross, D.Beresford, J.Tam, C.et al.2015-03-102015-03-102015Blood, 2015; 125(6):915-9230006-49711528-0020http://hdl.handle.net/2440/89658The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if <1000 ng/mL, imatinib 800 mg/day was given. Patients were then assessed against molecular targets: BCR-ABL1 ≤10%, ≤1%, and ≤0.1% at 3, 6, and 12 months, respectively. Cohort 1 patients failing any target escalated to imatinib 800 mg/day, and subsequently switched to nilotinib 400 mg twice daily for failing the same target 3 months later. Cohort 2 patients failing any target switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of patients remained on imatinib, and 30% on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64% at 12 months and 73% at 24 months. MR4.5 (BCR-ABL1 ≤0.0032%) at 24 months was 34%. Overall survival was 96% and transformation-free survival was 95% at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404.en© 2015 by The American Society of HematologyAustralasian Leukaemia and Lymphoma GroupHumansBenzamidesPiperazinesPyrimidinesFusion Proteins, bcr-ablProtein Kinase InhibitorsTreatment OutcomeSurvival AnalysisAdolescentAdultAgedAged, 80 and overMiddle AgedFemaleMaleLeukemia, Myelogenous, Chronic, BCR-ABL PositiveYoung AdultImatinib MesylateTIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targetsJournal article003001837810.1182/blood-2014-07-5903150003508177000092-s2.0-84922365224163889Yeung, D. [0000-0002-7558-9927]Osborn, M. [0000-0002-1288-9930]White, D. [0000-0003-4844-333X]Branford, S. [0000-0002-1964-3626] [0000-0002-5095-7981]Hiwase, D. [0000-0002-6666-3056]Ross, D. [0000-0001-7171-2935]Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]