Recent therapeutic approaches in myeloma

Bone disease is a frequent complication of multiple myeloma (MM) that is directly associated with quality of life and survival. Regarding the pathophysiology, osteocytes have a key role in the development of myeloma-related bone disease. Along with other factors they deregulate bone metabolism by increasing osteoclast activity, decreasing osteoblast function, and promoting an immunosuppressive bone marrow microenvironment. Bisphosphonates are the mainstay in the treatment of myeloma bone disease. However, a deeper insight in the underlying mechanisms of myeloma bone disease has resulted in the development of targeted therapeutic approaches. In this new era, denosumab, an RANKL inhibitor, has been proven noninferior to zoledronic acid in terms of preventing skeletal-related events (SREs), whereas it may confer a progression-free survival benefit among newly diagnosed MM patients eligible for autologous transplant. Denosumab may constitute a safer option for patients with impaired renal function; however, clinical studies including this patient group should be conducted. Indeed, these patients have a currently unmet medical need of being treated with specific bone-targeting agents along with the standard antimyeloma treatment, due to an excessive risk of developing SREs during the disease course. Furthermore, apart from inhibiting bone destruction, the reversal of bone damage remains a major challenge. Anabolic agents in combination with antiresorptive therapy, along with antimyeloma treatment, may be the key to restore bone metabolism in the myeloma microenvironment. Antisclerostin antibodies combined with zoledronic acid seem to be the most promising therapeutic approach to proceed in clinical evaluation in the near future.