Standard treatment of patients under the age of 65 with multiple myeloma is high dose melphalan followed by infusion of autologous blood stem cells (ASCT). Standard treatment of patients over the age of 65 is low dose melphalan and prednisolon. Most patie nts respond to this treatment, but patients will ultimately experience disease progression. If the response to melphalan-based treatment has been successful, this treatment can be repeated. However, most patients will develop melphalan resistance. There a re very few randomized trials which have been conducted in this group of patients with melphalan-resistance. There are several non-randomized phase 2 trials showing clear effects of thalidomide or bortezomib with or without steroids. In general, addition of steroids give higher rates of responses. One randomized trial (APEX) has compared bortezomib with high-dose dexamethasone in this group of patients, and showed a favorable outcome for patients receiving bortezomib.
Although both thalidomide and bortezo mib are used as second line treatment when melphalan-resistance develops, there are no available clinical trials comparing the effects of thalidomide and bortezomib in this situation.
We want to conduct a randomized phase 3 clinical trial comparing the e ffects of thalidomide and bortezomib, with addition of dexamethasone in both groups, in myeloma patients with melphalan-resistance. The trial will have a cross-over design when patients develop resistance for either study drug. The trial will be conducted without financial or other support from medical companies to secure full control of the implementation of the trial and the results. The trial will recruit a total of 300 patients from Sweden, Denmark and Norway. The investigators are all members of NMSG (Nordic Myeloma Study Group).