Xgeva Helps Delay Bone Complications Associated With Multiple Myeloma

One of the complications of multiple myeloma, a malignancy of plasma cells in the bone marrow, includes bone fractures and/or spinal cord compression. But a new treatment may offer bone protection to mitigate these issues.

A randomized, double-blind, multicenter trial compared Xgeva (denosumab, also marketed as Prolia), a monoclonal antibody that works as a RANK ligand (RANKL) inhibitor, with zoledronic acid in the prevention of bone complications in patients with newly diagnosed multiple myeloma. A total of 1,718 patients (859 on each arm) were randomized to receive either subcutaneous denosumab 120 mg and intravenous placebo every 4 weeks, or intravenous zoledronic acid 4 mg (adjusted for renal function) and subcutaneous placebo every 4weeks.

The phase III trial evaluating denosumab versus zoledronic acid met the primary endpoint of noninferiority (hazard ratio [HR], 0.98, 95% CI, 0.85-1.14) in delaying the time to first on-study skeletal-related events (SRE) in patients with multiple myeloma. The secondary endpoints of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met. The HR of denosumab versus zoledronic acid for overall survival was 0.90 (95% CI, 0.70-1.16).

The most common side events (greater than 25%) in the denosumab arm of the study were diarrhea and nausea. Fatigue, shortness of breath, muscle weakness, and hypophosphatemia can also occur.

"Many of these patients suffer from renal impairment, which has limited their treatment options," said Sean E. Harper, MD, executive vice president of Research and Development at Amgen, in a news release. "Xgeva's unique mechanism of action has the potential to prevent bone complications in multiple myeloma patients regardless of their renal status, fulfilling an important unmet medical need."

Additional complications include anemia and impaired immune function; reduced levels of white blood cells making fighting infections much more difficult.

Multiple myeloma is a relatively uncommon cancer. In the United States, the lifetime risk of getting multiple myeloma is 1 in 143 (0.7%), according to the American Cancer Society, which estimates that 30,330 new diagnoses will be made this year, and approximately 12,650 deaths from this disease or related complications.

Detailed results will be submitted for presentation an upcoming medical conference and for publication in a scientific journal.