The Food and Drug Administration (FDA) approves the supplemental Biologics License Application for denosumab (Xgeva, Amgen) to expand the currently approved indication for the prevention of skeletal-related events in multiple myeloma (MM) patients with bone metastases. The approval is based on data from the pivotal phase III randomized, double-blind, multicenter ‘482 trial, the largest international MM clinical trial, which enrolled 1,718 patients. The study met the primary endpoint, demonstrating non-inferiority of denosumab to zoledronic acid in delaying the time to first on-study skeletal-related event in MM patients (HR = 0.98; 95% CI: 0.85–1.14; P = .01). The secondary endpoints, delaying time to first skeletal-related event and delaying time to first-and-subsequent skeletal-related events, did not demonstrate superiority. Overall survival was comparable between denosumab and zoledronic acid, with an HR of 0.90 (95% CI: 0.70–1.16; P = .41). The median difference in progression-free survival (PFS) favored denosumab by 10.7 months (HR = 0.82; 95% CI: 0.68, 0.99; P = .036). Median PFS was 46.1 months (95% CI: 34.3 months, not estimable [NE], n = 219) for denosumab and 35.4 months (95% CI: 30.2 months, NE, n = 260) for zoledronic acid. Adverse events observed in patients treated with denosumab were generally consistent with the known safety profile of this drug.