Comparison of reduced-dose bortezomib plus thalidomide plus dexamethasone (vTD) to bortezomib plus dexamethasone (VD) as induction treatment prior to ASCT in de novo multiple myeloma (MM): Results of IFM2007-02 study.

Abstract

8014 Background: The IFM has shown that induction treatment prior to ASCT with VD is superior to VAD. The Italian group has presented impressive results regarding response rates with VTD (Cavo ASH 2009). In both studies, peripheral neuropathy (PN) was the most frequent adverse event (9% Grade 3). Methods: We conducted a randomized trial comparing four 21-day cycles of induction with VD (V 1.3 mg/m2/d on days 1,4,8,11 plus D 40 mg/d on days 1-4 and 8-11) or vTD (v 1 mg/m2/d on days 1,4,8,11 plus thalidomide 100 mg/d d1-21 plus dexamethasone same dosing as for VD). The primary objective was the CR rate after induction treatment. Secondary objectives were achievement ≥ VGPR and ≥ PR, and toxicity including incidence of PN. Results: From 03/2008 to 01/2009, 205 patients with de novo MM (< 66 years) were randomized. The two groups were well balanced as regards initial prognostic parameters. As of January 10, 2010, according to investigators'assessment, on an intent-to-treat basis, the post-induction efficacy results are the following (VD vs vTD): CR rate 12% vs 14% (p= 0.68), CR + nCR 22% vs 31% (p = 0.15), ≥ VGPR 36% vs 50 % (p=0.047), ≥ PR 81%vs 90% (p= 0.096), stable disease 12% vs 5%, progression/failure 7% vs 4%. The post-ASCT results are the following (VD vs vTD): CR + nCR rate 47 vs 60% (p = 0.50), ≥ VGPR 54 vs 66% (p = 0.044), ≥ PR 84 vs 92% (p = 0.33). There was no difference regarding toxicity between the 2 arms of the study, except for peripheral neuropathy (PN). Grade > 2 PN occurred in 28% of the cases in the VD arm vs 16% in vTD (p = 0.04), and treatment was interrupted due to PN in 4 cases of the VD arm vs 0 (p = .12). Conclusions: Four cycles of induction treatment with vTD are more effective than 4 cycles of VD, since CR+VGPR rate is superior both before and after ASCT. Despite the addition of thalidomide, the incidence of PN was markedly reduced in the vTD arm. vTD as induction prior to ASCT is a new alternative with a very good efficacy/toxicity ratio. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Janssen-Ortho