Intensification with autologous stem cell (ASCT) is currently the most effective treatment for subjects under 65 and the essential goal is to achieve complete response (CR) or very good partial response (VGPR= greater than 90% reduction of monoclonal component). However, only 50% of patients achieve this CR/VGPR even with tandem ASCT early in the course of disease. Optimization of the conditioning regimen could improve this CR/VGPR rate. The combinaison of Velcade and HD Melphalan has never been evaluated. However, at conventional doses, Velcade potentiates the antimyeloma effect of Melphalan without inducing any common toxicity.

This study will be conducted in patients under the age of 65 with de novo multiple myeloma or in first relapse, with Salmon and Durie stage of III, II, I with one symptomatic bone lesion (radiological)and no contraindication to intensification. The primary objective will be to increase the CR/VGPR rate 3 months after autologous peripheral blood stem cell transplantation conditioned by Velcade-Melphalan from 40% to 70%. With alpha=5% and bêta=10%, 61 patients will be included. Secondary objectives will be to assess the toxicity of the Velcade-Melphalan conditioning regimen, the progression-free survival and the overall survival after intensification. Response rates will be evaluated according to the response criteria defined by. Analysis will be performed on an intention-to-treat basis. After conventional induction therapy and PBSC collection, patients will be offered this new conditioning regimen. they will be free to refuse this regimen, in which case they will receive standard intensification therapy by Melphalan 200 mg/m² followed by autologous stem cell transplantation. Evaluation will occur at 3 months post intensification.