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 .
An open‐label, phase 2 trial of denosumab in the treatment of relapsed or plateau‐phase multiple myeloma
RANKL is a key mediator of osteoclast differentiation , activation , and survival . Pre clinical data suggest that aberrant production and activation of osteoclasts may influence proliferation of multiple myeloma ( MM ) cells in the bone marrow . Reports have also shown that inhibiting RANKL may have a direct effect on RANK‐expressing myeloma cells and a therapeutic role in treating the disease . In mouse myeloma models , inhibition of RANKL led to reduced serum paraprotein levels and tumor burden . Based on this hypothesis , this proof‐of‐concept , single‐arm study investigated whether RANKL inhibition with denosumab could reduce serum M‐protein levels in relapsed or plateau‐phase myeloma subjects . All subjects received denosumab monthly , with loading doses on days 8 and 15 of month one , until disease progression or subject discontinuation . Results of this ongoing study demonstrated that no subjects in either cohort met the protocol ‐defined objective response criteria of complete response ( CR ) or partial response ( PR ) , but that denosumab effectively inhibited the RANKL pathway regardless of previous exposure to bisphosphonates , as evidence d by suppressed levels of the bone turnover marker , serum C‐terminal telopeptide of type 1 collagen ( sCTx ) . Eleven ( 21 % ) subjects who relapsed within 3 months before study entry maintained stable disease for up to 16.5 months . Nineteen ( 46 % ) subjects with plateau‐phase myeloma maintained stable disease for up to 18.3 months . The adverse event ( AE ) profile for denosumab and its dosing schedule in these population s was consistent with that for advanced cancer patients receiving systemic therapy . Additional controlled clinical studies of denosumab in subjects with both relapsed and plateau‐phase MM are warranted . Am . J. Hematol . 2009 . © 2009 Wiley‐Liss ,
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 .