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).

1st Faculty of Medicine 1st Medical Department Clinical Department of Haematology Charles University Prague Prague Czech Republic

c o 1st Department of Medicine Centre for Oncology Haematology and Palliative Care Wilhelminen Cancer Research Institute Wilhelminenspital Vienna Austria

Centro de Investigación Médica Aplicada Clínica Universidad de Navarra Pamplona Spain

Department of Haemato oncology FN Ostrava and Faculty of Medicine Ostrava Czech Republic

Department of Haematology and Stem Cell Transplantation St István and St László Hospital Budapest Hungary

Division of Janssen Cilag Limited Janssen Research and Development High Wycombe UK

Hospital de Dia de Hematologia Hospital de Santa Maria Lisbon Portugal

IBMCC Hospital Universitario Salamanca CIC Salamanca Spain

Institut Paoli Calmettes Marseille France

Institute of Haematology Assuta Medical Centre Tel Aviv Israel

Janssen Global Services LLC Raritan NJ USA

Janssen Research and Development Division of Janssen Pharmaceutica NV Beerse Belgium

Janssen Research and Development LLC Spring House PA USA

Landeskrankenhaus Universitätsklinik für Innere Medizin 3 Salzburg Austria

Medical University of Lublin Lublin Poland

Serviço de Onco Hematologia Instituto Português de Oncologia do Porto Francisco Gentil Entidade Pública Empresarial Porto Portugal

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ClinicalTrials.gov
NCT00531453