Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial

We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade >= 3 adverse events were leucopenia (31.4%) and thrombocytopenia (6.8%). The overall response rate (ORR) by investigator-based assessment was 85.4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86.2% vs. 84.3%). Further follow-up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow-up, 55.5 months); median progression-free survival (PFS) was 35.3 months and median overall survival (OS) was not reached. In patients with high-risk versus standard-risk cytogenetics, median PFS was 19.9 vs. 43.6 months (P<0.0001), and median OS was 54.7 months versus not reached (P=0.0022). VCD is an effective and tolerable induction regimen; results suggest that VCD induces high response rates independently of cytogenetic risk status, but after long-term follow-up, cytogenetic high risk is associated with markedly reduced PFS and OS post-ASCT.