title: Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up.
abstract: This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio (HR) 1·26, 95% confidence interval: 0·76-2·09; P = 0·370]. Five-year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD-negative versus MRD-positive patients with bone marrow-confirmed complete response (HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453).
authors.affiliation: c/o First Department of Medicine, Centre for Oncology, Haematology and Palliative Care, Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Ludwig
authors.affiliation: Landeskrankenhaus, Universitätsklinik für Innere Medizin III, Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: Department of Haematology and Stem Cell Transplantation, St István and St László Hospital, Budapest, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.affiliation: First Faculty of Medicine, First Medical Department, Clinical Department of Haematology, Charles University in Prague, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Spicka
authors.affiliation: Institute of Haematology, Assuta Medical Centre, Tel-Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.affiliation: Department of Haemato-oncology, FN Ostrava and Faculty of Medicine, Ostrava, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Hajek
authors.affiliation: Medical University of Lublin, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Dmoszynska
authors.affiliation: Centro de Investigación Médica Aplicada (CIMA), Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: IBMCC (USAL-CSIC), Hospital Universitario Salamanca, CIC, Salamanca, Spain.
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Hospital de Dia de Hematologia, Hospital de Santa Maria, Lisbon, Portugal.
authors.forename: Graca
authors.initials: G
authors.lastname: Esteves
authors.affiliation: Institut Paoli-Calmettes, Marseille, France.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Stoppa
authors.affiliation: Janssen Global Services, LLC, Raritan, NJ, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Division of Janssen-Cilag Limited, Janssen Research & Development, High Wycombe, UK.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Ataman
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Enny
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Huaibao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Janssen Research & Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.affiliation: Serviço de Onco-Hematologia, Instituto Português de Oncologia do Porto Francisco Gentil, Entidade Pública Empresarial (IPOPFG, EPE), Porto, Portugal.
authors.forename: Luisa
authors.initials: L
authors.lastname: Viterbo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D064592:Autografts; D000069286:Bortezomib / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality* / Q000628:therapy*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage
chemical_list: D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide
keywords: minimal residual disease; multiple myeloma; transplantation