title: Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL.
abstract: ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. Two hundred and fifteen patients were recruited to assess the primary end point of complete remission (CR) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8 FCR vs 69.3% FCM-R (adjusted odds ratio (OR): 0.97; 95% confidence interval (CI): (0.53-1.79), P=0.932). MRD-negativity rates were 59.3 FCR vs 50.5% FCM-R (adjusted OR: 0.70; 95% CI: (0.39-1.26), P=0.231). During treatment, 60.0% (n=129) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy.
authors.affiliation: Department of Haematology, St James's University Hospital, Leeds, UK.
authors.forename: T
authors.initials: T
authors.lastname: Munir
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Howard
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: L
authors.initials: L
authors.lastname: McParland
authors.affiliation: Haematology, East Kent Hospitals, Canterbury, UK.
authors.forename: C
authors.initials: C
authors.lastname: Pocock
authors.affiliation: Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Rawstron
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hockaday
authors.affiliation: Department of Haematology, St James's University Hospital, Leeds, UK.
authors.forename: A
authors.initials: A
authors.lastname: Varghese
authors.affiliation: Haematology, Colchester Hospital University NHS Foundation Trust, Colchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Hamblin
authors.affiliation: Haematology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bloor
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pettitt
authors.affiliation: Haematology, University Hospital of Wales, Cardiff, UK.
authors.forename: C
authors.identifier: 0000-0001-9685-0621
authors.initials: C
authors.lastname: Fegan
authors.affiliation: Haematology, Royal Cornwall Hospital, Cornwall, UK.
authors.forename: J
authors.initials: J
authors.lastname: Blundell
authors.affiliation: Barts and The London NHS Trust, London, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Gribben
authors.affiliation: Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
authors.forename: D
authors.initials: D
authors.lastname: Phillips
authors.affiliation: Section of Experimental Haematology, Leeds Institute of Cancer and Pathology (LICAP), University of Leeds, Leeds, UK.
authors.forename: P
authors.initials: P
authors.lastname: Hillmen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual; D009503:Neutropenia / Q000188:drug therapy / Q000517:prevention & control; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D000069283:Rituximab; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine