The immune microenvironment and immunotherapy of multiple myeloma Ahead of print


1 Service d’hématologie, CHU de Lille, France
2 Service d’hématologie, CHU de Lille, France
* Tirés à part

Multiple myeloma evolves from a bone marrow clone of plasma cells and is always preceded by a pre-malignant condition. There is a continuum that ranges from monoclonal gammopathy of unknown significance, to smouldering multiple myeloma, to 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, haematopoietic stem cells, osteoblasts, osteoclasts, and immune cells such as B, T and NK lymphocytes, dendritic cells, macrophages and myeloid-derived suppressor cells. The dawn of immunotherapies has highlighted the importance of the immune system in MM oncogenesis. Reactivating the immune system is sufficient to induce a clear 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 describe the immune dysfunction and the main immunotherapies in MM.