SRE are a hallmark of MM and lead to increased morbidity and mortality. Via interactions with the BMME, MPC stimulate osteoclastogenesis which in turn leads to MPC survival and osteolytic bone lesions. Osteoclast inhibition with BPs, particularly ZA and pamidronate, is the standard of care in preventing and delaying SRE in MM as well as in prolonging OS due to their anti-myeloma properties. However, administration of BPs is challenging in MM patients due to their renal clearance, potential to cause nephrotoxicity and the inherent renal dysfunction associated with MM. RANKL is a key molecule in the BMME involved in osteoclastogenesis. Anti-myeloma therapies including PIs, immunomodulatory agents, high dose chemotherapy followed by ASCT and HDACs have been shown to inhibit osteoclastogenesis via inhibition of RANKL. Denosumab, a fully human monoclonal antibody against RANKL has proven to be noninferior to ZA in preventing and delaying SRE in MM. Denosumab has also shown to prolong PFS in MM patients compared to ZA. Favorable renal tolerance makes denosumab an attractive candidate for use in MM patients with renal disease. Vertebral fractures upon discontinuation of therapy represent an important toxicity and need to be monitored for carefully. Given the direct anti-MM effect observed in several studies, well planned clinical trials combining denosumab with novel immunotherapeutic approaches are desirable to expand the therapeutic armamentarium for MM.


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The authors report no conflicts of interest in this work.

Ricardo D Parrondo, Taimur Sher

Department of Medicine, Hematology-Oncology, Mayo Clinic Florida, Jacksonville, FL, USA

Correspondence: Taimur Sher
Department of Medicine, Hematology-Oncology, Mayo Clinic Florida, 4500 San Pablo Road S, Jacksonville, FL 32224, USA
Email sher.taimu[email protected]


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Source: OncoTargets and Therapy.
Originally published October 14, 2019.

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