MMY-3002: A Phase 3 Study Comparing Bortezomib-Melphalan-Prednisone (VMP) with Melphalan-Prednisone (MP) in Newly Diagnosed Multiple Myeloma.

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 β₂-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 1–4 of each cycle. Patients in the MP arm received 9 6-week cycles of MP once daily on days 1–4. 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 β₂-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.