Investigational agents in immunotherapy: a new horizon for the treatment of multiple myeloma

The treatment of multiple myeloma (MM) has gone through several major advances over the last 5 years with the introduction of next generation proteasome inhibitors (PI; carfilzomib, ixazomib) and immunomodulatory derivatives (IMiD; pomalidomide), with these new agents having a substantial impact on patient outcome. However, despite these advances, MM remains a highly resistant disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment. Almost all patients eventually relapse despite therapeutic responses to a PI, IMiD or both. With the regulatory approval of the monoclonal antibodies Daratumumab and Elotuzumab in 2015, impressive and durable responses are being observed, even in heavily pre-treated patients who have exhausted other therapeutic options, suggesting immunological approaches in this setting have real merit. This review will focus on newer monoclonal antibodies and chimeric-antigen receptor (CAR) T cell strategies currently under investigation and in various stages of clinical development.