General MM,   Relapsed/refractory patients,  Patients non-eligible for transplant

2017 ASCO Annual Meeting: Impact of denosumab compared with zoledronic acid on renal function for the treatment of bone disease in MM

The Multiple Myeloma Hub was happy to attend the 2017 ASCO Annual Meeting in Chicago, Illinois at McCormick Place from June 2nd to 6th, 2017. The meeting boasted attendance from oncology professionals worldwide. The Multiple Myeloma Hub is pleased to share results about the comparator trial of denosumab and zoledronic acid (ZA) in myeloma bone disease.

Professor Noopur Raje from Massachusetts General Hospital provided an excellent presentation on this subject. Osteolytic bone disease occurs in up to 90% of Multiple Myeloma (MM) patients. Denosumab is a monoclonal antibody against RANKL. RANKL is a key driver of osteoclast activity, which increases the risk of skeletal-related events (SRE), morbidity and mortality in MM. This trial is the largest study ever conducted in MM patients, enrolling 1718 patients from 259 sites and 29 countries. Denosumab was dosed at 120mg subcutaneously, and zoledronic acid 4mg IV, both given every 4 weeks.

Key Findings:

All data are given as denosumab treated vs. ZA treated:

  • Denosumab was non-inferior in time to first on-study SRE
  • Time to first SRE = 22.83 vs. 23.8 months (HR 95% CI = 0.98 (0.85, 1.14))
  • Time to first and subsequent SRE was the same
  • Overall survival (OS) = no significant difference
  • Progression free survival (PFS): 46.09 vs. 35.38 months (p=0.036)
  • Adverse events ≥ grade 3: 5.2% vs. 5.8%
  • Renal toxicity in all patients: 10% vs. 17.1%
  • Renal toxicity in patients with Clcr ≤60mL/min: 12.9% vs. 26.4%
  • Hypocalcemia: 16.9% vs. 12.4%
  • Osteonecrosis of the jaw, positively adjudicated: 4.1% vs. 2.8%

In conclusion, denosumab is non-inferior to zoledronic acid (ZA) in time to first skeletal-related event and the difference in overall survival was not significant. However, progression free survival was 10.7 months longer with denosumab therapy and renal toxicity was decreased.

Related articles on the MM Hub include the request for approval of denosumab by Amgen and the prolonged use of ZA.

References
  1. Noopur S. Raje et al. Hematologic Malignancies—Plasma Cell Dyscrasia. American Society of Clinical Oncology (ASCO®) Annual Meeting; 2017 June 2–6; Chicago, IL, USA. Abstract 8005.
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