Superiority of bortezomib, thalidomide and dexamethasone (VTD) as induction pre-transplantation therapy in multiple myeloma: a randomized phase III PETHEMA/GEM study
Mené sur 386 patients d'âge inférieur à 65 ans et atteints d'un myélome multiple, cet essai randomisé évalue l'ajout de bortezomib à une combinaison thalidomide/dexaméthasone en traitement d'induction préalable à une greffe
The PETHEMA/GEM conducted a trial to comparing bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus VBMCP/VBAD/bortezomib (VBMCP/VBAD/B) in patients ≤65 years with multiple myeloma. The primary end point was CR rate post-induction and post-ASCT. 386 patients were allocated to VTD (130), TD (127) or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs. 14%, p=0.001) or with VBMCP/VBAD/B (35% vs. 21%, p=0.01). In patients with high-risk cytogenetics the CR rate was also higher with VTD than with TD (35% vs. 0%, p=0.002) or with VBMCP/VBAD/B (35% vs. 22%, p=0.02). The median PFS was significantly longer with VTD (56.2 vs. 28.2 vs. 35.5 months, p=0.01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs. 24%, p=0.004) or with VBMCP/VBAD/B (46% vs. 38%, p=0.1). Patients with high-risk cytogenetics had a shorter PFS and OS in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and post-transplant CR rate and in a significantly longer PFS although not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior ASCT. The study was registered with www.ClinicalTrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).