Targeting the Bone Marrow Microenvironment

Unprecedented advances in multiple myeloma (MM) therapy during the last 15 years are predominantly based on our increasing understanding of the pathophysiologic role of the bone marrow (BM) microenvironment. Indeed, new treatment paradigms, which incorporate thalidomide, immunomodulatory drugs (IMiDs), and proteasome inhibitors, target the tumor cell as well as its BM microenvironment. Ongoing translational research aims to understand in more detail how disordered BM-niche functions contribute to MM pathogenesis and to identify additional derived targeting agents. One of the most exciting advances in the field of MM treatment is the emergence of immune therapies including elotuzumab, daratumumab, the immune checkpoint inhibitors, Bispecific T-cell engagers (BiTes), and Chimeric antigen receptor (CAR)-T cells. This chapter will review our knowledge on the pathophysiology of the BM microenvironment and discuss derived novel agents that hold promise to further improve outcome in MM.