Monoclonal antibodies against RANKL and sclerostin for myeloma-related bone disease: can they change the standard of care?

Abstract

Introduction: Over 80% of the patients with multiple myeloma (MM) develop myeloma bone disease (MBD) during the disease course. The clinical consequences include serious skeletal-related events (SRE) that impact survival and quality of life. Bisphosphonates are the mainstay in the treatment of MBD. Currently, new therapeutic strategies are being introduced and broaden the therapeutic options in MBD. Areas covered: The purpose of this review is to summarize the current clinical management of MBD and present novel data regarding monoclonal antibodies against the receptor activator of NF-kappa B ligand (RANKL) and sclerostin that may change the clinical practice. Expert opinion: Our better understanding of the pathophysiology of MBD has identified several factors as potential therapeutic targets. Recent data have shown that the RANKL inhibitor denosumab constitutes a new promising option. The non-inferiority compared with bisphosphonates in terms of SRE prevention, the potential survival benefit, the convenience of subcutaneous administration, and the favorable toxicity profile makes denosumab a valuable alternative for physicians in the current treatment of MBD. Anti-sclerostin antibodies are currently under clinical development. Further investigations are needed to address open questions in the field including the value of anabolic agents combined with anti-resorptive and anti-MM drugs in MBD.

• Authors: Martina Kleber, Ioannis Ntanasis-Stathopoulos, Meletios A Dimopoulos, Evangelos Terpos
• Journal: Expert review of hematology (Expert Rev Hematol) Vol. 12 Issue 8 Pg. 651-663 (08 2019) ISSN: 1747-4094 [Electronic] England
• PMID: 31268745 (Publication Type: Journal Article, Review)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antibodies, Monoclonal
• Bone Density Conservation Agents
• RANK Ligand
• SOST protein, human
• TNFSF11 protein, human
• Denosumab
• Zoledronic Acid

Topics

• Adaptor Proteins, Signal Transducing (immunology, metabolism)
• Antibodies, Monoclonal (therapeutic use)
• Bone Density Conservation Agents (therapeutic use)
• Bone Diseases (drug therapy, etiology)
• Denosumab (therapeutic use)
• Humans
• Multiple Myeloma (complications, pathology)
• RANK Ligand (immunology, metabolism)
• Zoledronic Acid (therapeutic use)