title: TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets.
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.
authors.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;
authors.forename: David T
authors.initials: DT
authors.lastname: Yeung
authors.affiliation: Department of Haematology, and Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
authors.forename: Michael P
authors.initials: MP
authors.lastname: Osborn
authors.affiliation: 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;
authors.forename: Deborah L
authors.initials: DL
authors.lastname: White
authors.affiliation: 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;
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.affiliation: Department of Genetics and Molecular Pathology and Centre for Cancer Biology, SA Pathology, Adelaide, Australia;
authors.forename: Jodi
authors.initials: J
authors.lastname: Braley
authors.affiliation: Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia;
authors.forename: Alan
authors.initials: A
authors.lastname: Herschtal
authors.affiliation: Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia;
authors.forename: Michael
authors.initials: M
authors.lastname: Kornhauser
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Middlemore Hospital, Auckland, New Zealand;
authors.forename: Samar
authors.initials: S
authors.lastname: Issa
authors.affiliation: Department of Haematology, and Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Hiwase
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Prince of Wales Hospital, Sydney, Australia; School of Medicine, University of Sydney, Sydney, Australia;
authors.forename: Mark
authors.initials: M
authors.lastname: Hertzberg
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Box Hill Hospital, Melbourne, Australia;
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Schwarer
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; St. Vincent's Hospital Melbourne, Melbourne, Australia;
authors.forename: Robin
authors.initials: R
authors.lastname: Filshie
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Royal North Shore Hospital, Sydney, Australia;
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Arthur
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Concord Hospital, Sydney, Australia;
authors.forename: Yiu Lam
authors.initials: YL
authors.lastname: Kwan
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; School of Medicine, University of Sydney, Sydney, Australia; Concord Hospital, Sydney, Australia;
authors.forename: Judith
authors.initials: J
authors.lastname: Trotman
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Gosford Hospital, Gosford, Australia;
authors.forename: Cecily J
authors.initials: CJ
authors.lastname: Forsyth
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; School of Medicine, University of Sydney, Sydney, Australia; Nepean Hospital, Penrith, Australia;
authors.forename: John
authors.initials: J
authors.lastname: Taper
authors.affiliation: Department of Haematology, and Discipline of Medicine, School of Medicine, University of Adelaide, Adelaide, Australia; Australasian Leukemia and Lymphoma Group, Melbourne, Australia;
authors.forename: David M
authors.initials: DM
authors.lastname: Ross
authors.affiliation: Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Beresford
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia;
authors.forename: Constantine
authors.initials: C
authors.lastname: Tam
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Princess Alexandra Hospital, Brisbane, Australia; and.
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Mills
authors.affiliation: Australasian Leukemia and Lymphoma Group, Melbourne, Australia; Department of Clinical Haematology, Austin Hospital and University of Melbourne, Melbourne, Australia.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Grigg
authors.affiliation: 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;
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib