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June 27, 2019

Denosumab vs Zoledronic Acid for Bone-Targeted Therapy in Multiple Myeloma: What Are the Unanswered Questions?

Author Affiliations
  • 1Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio
  • 2Multiple Myeloma Program, Cleveland Clinic, Cleveland, Ohio
JAMA Oncol. 2019;5(8):1095-1096. doi:10.1001/jamaoncol.2019.1598

Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by end-organ damage with osteolytic lesions, anemia, renal failure, and hypercalcemia. Bone lesions are present in 70% to 80% of patients at diagnosis and increase the risk of subsequent skeletal-related events (SREs). Intravenous bisphosphonates, namely, zoledronic acid and pamidronic acid, were available options for bone-targeted therapy in MM in the United States until January 2018, when denosumab (inhibitor of receptor activator of nuclear factor-κB ligand) was approved by the US Food and Drug Administration (FDA) based on the phase 3 noninferiority XGEVA Study 20090482 (‘482).1 The FDA label for denosumab indicates that it can be used for prevention of SREs in MM. The approval was followed by an American Society of Clinical Oncology (ASCO) guideline update, which added denosumab as an alternative to bisphosphonates and endorsed its use in the setting of renal compromise.2 Although, to the best of our knowledge, exact estimates on the market uptake of denosumab by oncologists have not yet been reported, much has been published debating the cost and/or value of substituting zoledronic acid with denosumab. Here, we will make 4 arguments apart from cost-effectiveness that, in our opinion, should instill skepticism regarding routinely substituting zoledronic acid with denosumab in all patients with newly diagnosed MM.