title: The role of denosumab for prevention of skeletal-related complications in multiple myeloma.
abstract: OBJECTIVE
  To evaluate the use of denosumab for the prevention of skeletal-related events (SREs) in patients with osteolytic lesions associated with multiple myeloma (MM).
  
  
  METHODS
  MEDLINE/Ovid (1946-April week 3, 2013), EMBASE (1980-2013 week 16), abstracts of the American Society of Clinical Oncology (1983-April 22, 2013), American Society of Hematology (2004-April 22, 2013), European Hematology Association (1994-April 22, 2013), and the European Society for Medical Oncology (1990-April 22, 2013) were searched using the terms denosumab and multiple myeloma.
  
  
  METHODS
  Clinical trials comparing the efficacy of denosumab with that of bisphosphonates in preventing or delaying SREs in patients with MM were included. Trials solely evaluating bone turnover markers were excluded. One Phase 2 trial, 1 Phase 3 trial, and 1 post hoc Phase 3 analysis were included.
  
  
  RESULTS
  A Phase 2 trial compared denosumab to bisphosphonate continuation in patients with elevated urinary N-telopeptide levels (uNTX) despite bisphosphonate therapy. Denosumab patients experienced fewer SREs; however, this was not statistically significant. A Phase 3 trial compared denosumab to zoledronic acid in patients with at least 1 osteolytic lesion. Denosumab delayed the time to a first SRE by 16% (median 20.6 vs 16.3 months; p = 0.0007 for noninferiority). Superiority of denosumab was not reached. A post hoc analysis revealed less favorable survival in MM patients treated with denosumab (HR 2.26; 95% CI 1.13-4.50). The incidence of overall adverse effects was similar between each group in both studies.
  
  
  CONCLUSIONS
  Denosumab may be an alternative for the prevention of SREs in patients with MM with deteriorating renal function. Because of the high cost of the drug, low percentage of MM patients in the available studies, and the potential for their decreased survival, use of denosumab should be limited.
authors.affiliation: Global Medical Affairs, Sanofi Oncology, Cambridge, MA, USA. kellymhageman@gmail.com
authors.forename: Kelly
authors.initials: K
authors.lastname: Hageman
authors.forename: Kiki Chandni
authors.initials: KC
authors.lastname: Patel
authors.forename: Kimberly
authors.initials: K
authors.lastname: Mace
authors.forename: Maryann R
authors.initials: MR
authors.lastname: Cooper
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D000069448:Denosumab; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D010014:Osteolysis / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control*; D053245:RANK Ligand / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D000069448:Denosumab