J.F. San Miguel, R. Schlag, N. Khuageva, O. Shpilberg, M. Dimopoulos, M. Kropff, I. Spicka, M. Petrucci, O. Samoilova, A. Dmoszynska, K. Abdulkadyrov, R. Schots, B. Jiang, A. Palumbo, M. Mateos, K. Liu, A. Cakana, H. Van de Velde, P. Richardson Hospital Universitario de Salamanca, Spain; Praxisklinik Dr. Schlag, Wrzburg, Germany; SP Botkin Moscow City Clinical Hospital, Russian Federation; Rabin Medical Center, Petah-Tiqva, Israel; University of Athens School of Medicine, Greece; University of Mnster, Germany; University Hospital Prague, Czech Republic; University La Sapienza, Rome, Italy; Nizhnii Novgorod Region Clinical Hospital, Russian Federation; Medical University of Lublin, Poland; St Petersburg Clinical Research Institute of Hematology Transfusiology, Russian Federation; Myelome Study Group Belgian Hematological Society, Belgium; Peoples Hospital, Peking University, China; Universita di Torino, Italy; Johnson Johnson PRD, Raritan, USA; Johnson Johnson PRD, Beerse, Belgium; Dana-Farber Cancer Institute, Boston, USA

Background: In a phase 1/2 trial of VMP in 60 newly diagnosed MM patients (median age 75 years), the CR/nCR rate was 43%, with 32% CR; the 3-year survival was 85% (Mateos et al, Blood 2006; Mateos et al, EHA/IMW 2007). MMY-3002 is a phase 3 study comparing VMP with standard MP in patients with previously untreated MM who are not candidates for high-dose chemotherapy/stem-cell transplant. Methods: Approximately 680 patients were randomized to VMP or MP and stratified according to baseline 2-microglobulin and albumin, and geographic region. Eligibility criteria required the presence of measurable disease, KPS 60% and hematology/chemistry laboratory values meeting predefined criteria. Patients in the VMP arm received intravenous bortezomib 1.3mg/m2 twice weekly (weeks 1, 2, 4, 5) for four 6-week cycles (8 doses per cycle), followed by once weekly (weeks 1, 2, 4, 5) for five 6-week cycles (4 doses per cycle) in combination with oral melphalan 9mg/m2 and prednisone 60mg/m2 once daily on days 14 of each cycle. Patients in the MP arm received 9 6-week cycles of MP once daily on days 14. For both groups, treatment continued for a maximum of 9 cycles (54 weeks) unless disease progression or unacceptable treatment-related toxicity occurred. The primary endpoint was time to progression (TTP), and secondary endpoints included progression-free survival (PFS), overall survival (OS), overall response rate, time to and duration of response, and safety. Results: Between December 2004 and September 2006, 682 patients from 151 centers in 22 countries across Europe, North and South America, and Asia were randomized. The median age was 71 years with 30% of patients aged 75 years. Fifty percent were male and 88% were of Caucasian origin. Median KPS was 80%, and 34% of patients had KPS 70%. Sixty-three percent had IgG myeloma, 25% had IgA myeloma, and 8% had light-chain disease. Bone involvement with >10 lytic bone lesions was reported in 27% of patients, 33% had 2-microglobulin >5.5mg/L, and 60% had albumin <35g/L. The study population therefore included a high proportion of patients with advanced disease and high-risk factors. The Independent Data Monitoring Committee is scheduled to review data from a pre-planned interim analysis to determine whether TTP was significantly longer with VMP vs MP and therefore whether the protocol-specified statistical boundary for the primary endpoint has been reached. Conclusion: Efficacy and safety analyses will be reported at the meeting.