The immune microenvironment and immunotherapies in multiple myeloma

Multiple myeloma evolves from a bone marrow clone of plasma cells and is always preceded by a pre-malignant condition. There is a continuum between precursor diseases named gammopathy monoclonal of undetermined significance and smoldering multiple myeloma and multiple myeloma (MM). It represents a model of clonal evolution and evolution of the microenvironment, with well defined clinical stages. The bone marrow microenvironment is constituted of stromal cells, hematopoietic stem cells, osteoblast, osteoclast, and immune cells such as B, T and NK lymphocytes, dendritic cells, macrophages, and myeloid derived suppressor cells. The breakthrough of Immunotherapies has highlighted the importance of immune system in MM oncogenesis. Reactivating the immune system is enough to induce deep response in clinical settings. Several immunotherapies are now essential treatments in MM, such as immunomodulators (thalidomide, lenalidomide, pomalidomide, iberdomide), anti-CD38 (daratumumab and isatuximab), CAR-T cells and bispecific antibodies. In this article we will describe the immune dysfunction and the main immunotherapies in MM.