For eligible individuals with multiple myeloma, high-dose melphalan (HDM) and transplantation were indicated. There was no other fitness plan that had been shown to be more effective and/or safer. In a phase 2 research, researchers previously found that bortezomib may be safely and successfully coupled with HDM (Bor-HDM), with a 32% complete response (CR) rate following transplantation. The findings were backed by a randomized phase 3 experiment. About 300 patients were enrolled, and 154 were assigned to the experimental arm (ie, arm A), which received bortezomib (1 mg/m2 IV) on days -6, –3, +1, and +4 and melphalan (200 mg/m2 IV) on the day –2. The control arm (i.e., arm B) consisted only of HDM (200 mg/m2 IV).
At day 60 posttransplant (primary endpoint), there were no differences in severe CR + CR rates: 22.1% in limb A versus 20.5% in arm B (P=.844). There were no variations in undetectable minimal residual disease rates: 41.3 vs 39.4 % (P=.864). The median progression-free survival for arm A was 34.0 months compared to 29.6 months for arm B (adjusted HR, 0.82; 95% CI, 0.61-1.13; P=.244). Both arms had an estimated 3-year overall survival rate of 89.5% (hazard ratio, 1.28; 95% CI, 0.62-2.64; P=.374). In 18.7% of Bor-HDM–treated individuals, 69 significant adverse events occurred (vs 13.1% in HDM-treated patients). The proportion of grade 3/4 AEs was comparable in both groups (72.0% vs 73.1%), with the majority being (as predicted) blood and gastrointestinal issues; 4% of patients had grade 3/4 or painful peripheral neuropathy in arm A. (vs 1.5% in arm B). A conditioning regimen with Bor-HDM had no effect on effectiveness endpoints or outcomes in the randomized phase 3 trial when compared to HDM alone.
