8505 Background: ASCT is the standard of care for MM patients (pts) aged ≤65 yrs with high complete plus very good partial remission (CR+VGPR) rate. Improving CR rate has been associated with prolonged PFS and OS. Phase 2 studies have shown bortezomib (VELCADE)/dexamethasone (Vel/Dex) as an effective induction therapy. Methods: In this phase 3 study, Vel/Dex (4 cycles) was compared with vincristine/doxorubicin/dexamethasone (VAD; 4 cycles) as induction prior to ASCT in 482 MM pts aged ≤65 years. Primary objective was CR+near-CR (nCR) rate. Planned enrolment (480 pts) provided 80% power to detect a 10% difference in CR+nCR rate (10% vs 20%). Consolidation with 2 cycles of Dex, cyclophosphamide, etoposide, platinum (DCEP) was also evaluated. Pts were randomized to 4 arms: A1: VAD (N=121), A2: VAD+DCEP (N=121), B1: Vel/Dex (N=121), and B2: Vel/Dex+DCEP (N=119). Results: In the intent-to-treat analysis (ITT) Vel/Dex had significantly higher CR+nCR/≥VGPR vs VAD post-induction (21.3%/46.7% vs 8.3%/18.6%, P=0.0023/<0.0001); Vel/Dex was also superior in pts with >3mg/L or ≤3mg/L β2M and in pts with or without del(13). The significant CR+nCR/≥VGPR Vel/Dex advantage was maintained post-ASCT, both in pts who received ASCT (40.8%/71.8% vs 28.8%/51%, P=0.0089/<0.0001) and in the ITT population (35%/61.7% vs 23.6%/41.7%, P=0.0056/<0.0001); DCEP did not increase response rates. During induction, grade ≥3 adverse events (AEs) rates were similar with Vel/Dex and VAD (38.2% vs 40.6%); serious AE rates (25.2% vs 31.0%) and AEs leading to death (0.8% vs 2.9%) were lower with Vel/Dex, while neuropathic symptoms (all grades) were higher with Vel/Dex (35.3% vs 22.6%). Stem cell collection was adequate (>2×106 CD34+/kg) in 97% and 99% of Vel/Dex and VAD pts, respectively. First analyses of the survival data will be presented at the meeting. Conclusion: Vel/Dex significantly improved post-induction response rates vs VAD, which translated into significantly better ≥VGPR rates post-ASCT. Vel/Dex should now be considered the standard induction treatment prior to ASCT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Millennium Celgene, Jansen Cilag, Pharmion Millennium Celgene, Jansen Cilag, Ortho Biotech, Pharmion
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Harousseau et al. (2008) studied this question.