Triple Combination Superior in Progressing or Relapsing Multiple Myeloma Post-ASCT
(ChemotherapyAdvisor) –The triple combination bortezomib-thalidomide-dexamethasone was found to be more effective than the dual combination of thalidomide-dexamethasone in patients with multiple myeloma who progressed or relapsed after autologous transplantation, and “may be considered a new standard of care for this subpopulation of patients,” according to a randomized Phase 3 study in the Journal of Clinical Oncology online May 14.
However, the triple combination was associated with a higher incidence of grade 3 neurotoxicity (29% vs. 12%; P=0.001), the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation MMVAR/IFM 2005-04 trial investigators noted.
In this study, 269 patients were randomly assigned to receive bortezomib (1.3mg/m2 IV bolus) 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 administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for 8 cycles (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, was significantly longer with bortezomib-thalidomide-dexamethasone than thalidomide-dexamethasone (19.5 vs. 13.8 months; HR, 0.59; P=0.001). In addition, the complete response plus near-complete response rate was higher with 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 grades 3 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-dexamethasone combination.”Abstract