Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12540
Title: TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets.
Authors: Yeung, David T;Osborn, Michael P;White, Deborah L;Branford, Susan;Braley, Jodi A;Herschtal, Alan;Kornhauser, Michael;Issa, Samar;Hiwase, Devendra K;Hertzberg, Mark;Schwarer, Anthony P;Filshie, Robin;Arthur, Christopher K;Kwan, Yiu Lam;Trotman, Judith;Forsyth, Cecily J;Taper, John;Ross, David M;Beresford, Jennifer;Tam, Constantine;Mills, Anthony K;Grigg, Andrew P ;Hughes, Timothy P
Institutional Author: Australasian Leukaemia and Lymphoma Group
Affiliation: Department of Haematology, and Department of Genetics and Molecular Pathology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia; Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Cancer Theme, South Australia Health and Medical Research Institute, Adelaide, Australia;
Department of Genetics and Molecular Pathology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia; Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; School of Molecular and Biomedical Science, and School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia;
Department of Genetics and Molecular Pathology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Middlemore Hospital, Auckland, New Zealand;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Prince of Wales Hospital, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Box Hill Hospital, Melbourne, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; St. Vincent's Hospital Melbourne, Melbourne, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Royal North Shore Hospital, Sydney, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Concord Hospital, Sydney, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; School of Medicine, University of Sydney, Sydney, Australia; Concord Hospital, Sydney, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Gosford Hospital, Gosford, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; School of Medicine, University of Sydney, Sydney, Australia; Nepean Hospital, Penrith, Australia;
Department of Haematology, and Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia;
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Princess Alexandra Hospital, Brisbane, Australia; and.
Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Department of Clinical Haematology, Austin Hospital and University of Melbourne, Melbourne, Australia.
Department of Haematology, and Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Cancer Theme, South Australia Health and Medical Research Institute, Adelaide, Australia;
Issue Date: 17-Dec-2014
Citation: Blood 2014; 125(6): 915-23
Abstract: The 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.
Internal ID Number: 25519749
URI: http://ahro.austin.org.au/austinjspui/handle/1/12540
DOI: 10.1182/blood-2014-07-590315
URL: http://www.ncbi.nlm.nih.gov/pubmed/25519749
Type: Journal Article
Subjects: Adolescent
Adult
Aged
Aged, 80 and over
Benzamides.administration & dosage.adverse effects.therapeutic use
Female
Fusion Proteins, bcr-abl.analysis
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive.drug therapy
Male
Middle Aged
Piperazines.administration & dosage.adverse effects.therapeutic use
Protein Kinase Inhibitors.administration & dosage.adverse effects.therapeutic use
Pyrimidines.administration & dosage.adverse effects.therapeutic use
Survival Analysis
Treatment Outcome
Young Adult
Appears in Collections:Journal articles

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