Wei-Chih Chen, Abraham S Kanate, Michael Craig, William P Petros, Lori A Hazlehurst

Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM. Elotuzumab is a humanized monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7), approved by the US Food and Drug Administration (FDA) in 2015 and the European Medicines Agency in 2016 for the treatment of MM. SLAMF7 is expressed in normal and malignant plasma cells and has lower expression on natural killer (NK) cells. Experimental evidence indicates that elotuzumab exhibits anti-myeloma activity through 1) antibody-dependent cell-mediated cytotoxicity, 2) enhancing NK cells cytotoxicity and 3) interfering with adhesion of MM cells to bone marrow stem cells (BMSCs). Although elotuzumab has no single agent activity in patients with RRMM who have received one to three prior therapies, the combination of elotuzumab with anti-myeloma agents, such as immunomodulatory drugs-lenalidomide, or proteasome inhibitors (PIs)-bortezomib, remarkably improved the overall response rates and progression-free survival in MM patients with only minimal incremental toxicity. In brief, the clinical data for elotuzumab indicate that targeting SLAMF7 in combination with the use of conventional therapies is feasible and effective with a tolerable safety profile for the treatment of RRMM.