The triple combination therapy of bortezomib, thalidomide and dexamethasone was an effective treatment in patients with multiple myeloma who relapsed after autologous stem cell transplantation, but the therapy also was associated with significantly greater rates of neurotoxicity, according to the results of a phase 3 trial.
In the MMVAR/IFM 2005-04 study, an initiative of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation, researchers examined the efficacy of bortezomib — a proteasome inhibitor approved for treatment of multiple myeloma in the relapse setting — in patients who relapsed after autologous stem cell transplantation.
The study included 269 patients who had progressed or relapsed after one or more transplantation. Patients were enrolled at 60 centers and randomly assigned to 1-year’s treatment. Of the 269 patients, 135 were assigned to bortezomib, thalidomide and dexamethasone, and 134 were assigned to thalidomide and dexamethasone alone.
Median follow-up was 30 months. The primary endpoint was time to progression.
At follow-up, patients assigned to bortezomib had a longer time to progression compared with those assigned to thalidomide and dexamethasone alone (19.5 months vs. 13.8 months). Patients assigned to bortezomib had a 41% reduced risk for disease progression (P=.001). In addition, bortezomib conferred a longer median PFS (8.3 months vs. 13.6 months).
Patients assigned to bortezomib had a complete response rate of 45% compared with 25% without bortezomib (P=.001). The duration of this complete response also was longer in the bortezomib arm (17.2 months vs. 13.4 months; P=.003).
When looking at safety outcomes, data indicated that bortezomib also resulted in higher rates of grade-3 and grade-4 infection and thrombocytopenia, and significantly higher rates of grade 3 neuropathy (29% vs. 12%; P=.001).
Although the researchers wrote that the neuropathy was an “issue of concern requiring appropriate dose reduction,” they concluded that this triple combination therapy “may be considered a new standard of care for this subpopulation of patients.”
- Garderet L. J Clin Oncol. 2012;doi10.1200/JCO.2011.37.4918.