(ChemotherapyAdvisor)–The triple combination bortezomib-thalidomide-dexamethasone was found to bemore effective than the dual combination of thalidomide-dexamethasone inpatients with multiple myeloma who progressed or relapsed after autologoustransplantation, and “may be considered a new standard of care for thissubpopulation of patients,” according to a randomized Phase 3 study in the Journal of Clinical Oncology online May14.
However, thetriple combination was associated with a higher incidence of grade 3neurotoxicity (29% vs. 12%;P=0.001), the ChronicLeukemia Working Party of the European Group for Blood and MarrowTransplantation MMVAR/IFM2005-04 trial investigatorsnoted.
In this study,269 patients were randomly assigned to receive bortezomib (1.3mg/m2 IVbolus) or no bortezomib for 1 year, plus thalidomide (200mg/day orally) and dexamethasone(40mg orally once daily on 4 days once every 3 weeks). Bortezomib was administeredon days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for 8cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period(day 23 to day 42) for 4 cycles (6 months).
Median time to progression, the primary endpoint, wassignificantly longer with bortezomib-thalidomide-dexamethasone than thalidomide-dexamethasone(19.5 vs. 13.8 months; HR,0.59; P=0.001). Inaddition, the complete response plus near-complete response rate was higherwith the triple combination (45% vs.25%; P=0.001),and median duration of response was longer (17.2 vs. 13.4 months; P=0.03). The 24-month survival rate favored bortezomib-thalidomide-dexamethasone(71% vs. 65%;P=0.093). Rates of grades3 and 4 infection and thrombocytopenia were higher with the triple combination.
The study authors noted that in light of the higher rates of neurotoxicity,“we suggest a starting dose of 100mg per day thalidomide for the bortezomib-thalidomide-dexamethasonecombination.”