[Immunopathogenesis and appropriate use of monoclonal antibody agents in multiple myeloma]

Multiple myeloma (MM) involves the immune dysregulation not only of B cells but also of NK, T, and dendritic cells. Furthermore, the number of regulatory T and myeloid-derived immunosuppressive cells, which are associated with disease progression, also increases. Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide exhibit an antimyeloma effect and improve the immune status. Thus, IMiD-enhanced antibody-dependent cell cytotoxicity increases the cytotoxic activity of monoclonal antibody treatment. Among many antibodies, anti-SLAMF7 elotuzumab and anti-CD38 daratumumab have been approved in Japan, and their targeted antigens are responsible for functions that may influence clinical efficacy. Daratumumab exerts various mechanisms of antitumor activity and enhances T-cell immunity by inhibiting immunosuppressive cells. New monoclonal antibodies, including the anti-CD38 antibody isatuximab and anti-BCMA antibody-drug conjugate, are being developed and are expected to demonstrate clinical efficacy. To improve long-term prognosis and achieve cure for MM, immunotherapies such as IMiD-intensified antibody treatment, which resulted in better response rates and longer survival in refractory/relapsed MM, are essential.