Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative .
Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting .
Purpose To up date guideline recommendations on the role of bone-modifying agents in multiple myeloma .
Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma.
OBJECTIVES Bone disease is a key presenting feature of myeloma . This post hoc analysis of the phase III VISTA trial of bortezomib plus melphalan-prednisone ( VMP ) vs. MP in previously untreated myeloma patients assessed clinical bone disease events and changes in alkaline phosphatase ( ALP ) , a marker for osteoblast activation , and serum Dickkopf-1 ( DKK-1 ) , an inhibitor of osteoblast differentiation , during treatment . METHODS Patients received nine 6-wk cycles of VMP ( bortezomib 1.3 mg/m(2 ) , days 1 , 4 , 8 , 11 , 22 , 25 , 29 , 32 , cycles 1 - 4 , days 1 , 8 , 22 , 29 , cycles 5 - 9 , plus melphalan 9mg/m(2 ) and prednisone 60mg/m(2 ) , days 1 - 4 , cycles 1 - 9 ; N=344 ) or MP alone ( N=338 ) . RESULTS Rates of bisphosphonates use during treatment ( 73 % vs. 82 % ) , progression because of worsening bone disease ( 3 % vs. 11 % ) , and requirement for subsequent radiotherapy ( 3 % vs. 8 % ) were lower with VMP vs. MP . Median maximum ALP increase was significantly higher with VMP vs. MP overall ( 49.7 % vs. 30.3 % , P=0.029 ) , and higher by response group ( complete response [ CR ] : 68.7 % vs. 43.9 % ; partial response [ PR ] : 41.5 % vs. 31.2 % ) . Greater maximum ALP increase was strongly associated with achievement of CR ( P≤0.0001 ) and CR/PR ( P≤0.01 ) . Median DKK-1 decreased with VMP by 694.4pg/mL and increased with MP by 1273.3pg/mL from baseline to day 4 ( P=0.0069 ) . Available radiologic data revealed evidence of bone healing in 6/11 VMP-treated patients , who achieved best responses of three CR , one PR , and two stable disease . CONCLUSIONS These results suggest a positive effect of bortezomib on bone metabolism and potentially bone healing in myeloma
Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative .
Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting .
Purpose To up date guideline recommendations on the role of bone-modifying agents in multiple myeloma .