The Evolving Role of Checkpoint Inhibitors in Multiple Myeloma

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by production of abnormal levels of a monoclonal immunoglobulin or plasma cell deposition that leads to end organ destruction. The disease remains incurable despite advances in combination treatments with classes of medications that include proteosome inhibitors, immunomodulating agents, monoclonal antibodies, small molecule inhibitors, alkylating agents, T-cell-based immunotherapies, and others. Checkpoint inhibitors (CKP-I), though showing robust efficacy in solid tumor and lymphoma, have had limited success as single agents in the treatment of MM. Furthermore, early FDA holds on trials involving CKP-I in myeloma led to diminished enrollment and data on its potential use. Nevertheless, clearer understanding of the mechanisms of immune dysregulation and unique bone marrow biology in the pathophysiology of MM have opened the opportunity for future uses of CKP-I in multiple myeloma. Herein we provide a comprehensive review of the immunologic basis of multiple myeloma, preclinical and published data from trials utilizing CKP-I in MM patients, and future targets in CKP-I development that may provide promising opportunities in the treatment of MM.