Two prospective, phase II trials and one prospective randomized phase III trial have evaluated the efficacy of bortezomib in the treatment of patients with relapsed or refractory MM. Overall response rates for single agent bortezomib are approximately 30%. Bortezomib has also been evaluated in combination with dexamethasone with overall response rates of approximately 65%.
At a planned interim analysis, the APEXrr study was terminated early and patients receiving dexamethasone were offered therapy with bortezomib. At the time of early termination of the study, at a median follow-up of 8.3 months, patients receiving bortezomib experienced prolonged median time to progression of disease (6.2 versus 3.5 months), prolonged survival (hazard ratio 0.57), and higher response rates (complete or partial responses) (38 versus 18%) compared with those receiving dexamethasone. Overall survival was prolonged in patients receiving bortezomib, both for those who had received one prior treatment (hazard ratio 0.39) and for those who had received more than one prior treatment (hazard ratio 0.65).The median duration of response was 8 months in patients receiving bortezomib and 5.6 months in patients receiving dexamethasone. A higher response rate was observed in patients receiving bortezomib regardless of baseline ß2-microglobulin concentration.
256 patients with relapsed or refractory myeloma were enrolled in SUMMIT (n=202) and CREST (n=54). Overall 41% (n=106; 78 SUMMIT, 28 CREST) patients had dexamethasone added to the initial bortezomib therapy after the 2nd to 4th cycle. 13% of the patients in the SUMMIT study who received combination therapy demonstrated improved response, with 5 achieving PR following minimal or no response to bortezomib alone. Of the 28 patients on the CREST study who received combination therapy, 33% (9) demonstrated improved response. In relation to the timing of the addition of the dexamethasone, 14.7% of those who commenced on or before the 4th cycle demonstrated improved response, compared to 25.4% of those who commenced following cycle 4.r