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

Abstract

The treatment of multiple myeloma (MM) has gone through several major advances over the last 5years 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.