Elotuzumab as a novel anti-myeloma immunotherapy

Abstract

Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma. Although preclinical data looked very promising, elotuzumab monotherapy did not result in objective clinical responses in patients with relapsed/refractory multiple myeloma. However, combination treatment with immunomodulators and proteasome inhibitors resulted in substantial clinical activity in relapsed/refractory MM. Currently, there are several clinical trials ongoing investigating the role of elotuzumab in newly diagnosed myeloma patients and in patients receiving maintenance therapy.

Keywords: CS1; SLAM family of receptors; antibodies; elotuzumab; immunotherapy; monoclonal; multiple myeloma.

Figure 1.

Mechanisms of action of elotuzumab in Multiple myeloma. Elotuzumab mediates antibody dependent cell mediated cytotoxicity of CS1 expressing myeloma cells by natural killer cells (NK cells) and also activates NK cells by binding to CS1. Elotuzumab also decreases the adhesion of myeloma cells to bone marrow stromal cells (BMSC) but the mechanism is not well elucidated.