To evaluate denosumab’s effects on bone resorption and its safety in adults with multiple myeloma and creatinine clearance below 30 mL/min who were ineligible for bisphosphonate therapy.
Approach:
Design and treatment: Prospective, open-label, multicenter phase 2 study. Participants received denosumab 120 mg subcutaneously every four weeks for 12 cycles, with calcium and vitamin D supplementation.
Participants and outcomes: Twenty-four patients enrolled at six sites; 22 received denosumab and were included in outcome analyses. The primary endpoint was change in serum CTX at three months; safety and adverse events were secondary endpoints.
Key Findings:
Median serum CTX decreased by 73% at three months (n=18; p=0.0002).
Three patients experienced skeletal-related events; one-year skeletal-related-event-free survival was 85.4% (95% CI, 71.4–100%).
Hypocalcemia and infection were the most frequent adverse events (77.3% each). Grade 3 or higher hypocalcemia and neutropenia each occurred in 31.8%; infection occurred in 22.7%.
Four patients received intravenous calcium for hypocalcemia. Denosumab was held for hypocalcemia in seven patients; all restarted treatment after a mean interruption of 64 days.
Baseline CTX was inversely correlated with the lowest calcium concentration during treatment (Spearman ρ=−0.77; p=0.0002). Grade 2 or higher hypocalcemia was observed in 7/9 dialysis patients and 5/13 patients not receiving dialysis.
Interpretation:
The authors report a significant reduction in serum CTX in this cohort. Hypocalcemia was frequent; the authors note that dialysis patients tended to have a greater likelihood of grade 2 or higher hypocalcemia than patients not receiving dialysis.
Limitations:
Small sample size.
Early study closure because of slow accrual.
The study included both newly diagnosed and relapsed multiple myeloma.
Conclusion:
The authors describe this as the first prospective trial specifically evaluating denosumab in multiple myeloma patients with creatinine clearance below 30 mL/min.
by Elizabeth K. O’Donnell, Omar Nadeem, Jacob P. Laubach, Giada Bianchi, Andrew R. Branagan, Brea C. Lipe, Paul G. Richardson, Ehsan Malek, Robb S. Friedman, Ajay K. Nooka, Robert Redd, Noopur S. Raje, Andrew J. Yee
Baptist Health Cancer Care continues to expand access to specialized cancer care in Palm Beach County with a new Lynn Cancer Institute location in Boynton Beach, offering medical oncology, hematology and infusion services for patients with cancer and blood disorders.
