NEJM: Elotuzumab is a first immunoglobulin against lymphocytic activation

Baku. 20 July. REPORT.AZ/ Multiple myeloma, a malignant disease of monoclonal plasma cells, has a median overall survival of approximately 5 years. Despite improvements in treatment outcomes with proteasome inhibitors and immunomodulatory drugs, most patients continue to have a relapse, and new treatment approaches are needed. Combination therapy may be key to overcoming drug resistance and improving long-term treatment outcomes, Report informs 'The New England Journal of Medicine' (NEJM) writes.

Lenalidomide, an immunomodulatory drug, in combination with dexamethasone is a standard regimen in patients with relapsed or refractory disease. Three-drug combinations are emerging for patients with previously treated multiple myeloma but may be limited by toxic effects. Agents with new mechanisms of action that can be combined with existing therapies without an increase in serious toxicity are needed.

According to the article of the publication, Elotuzumab is a first-in-class humanized immunoglobulin G1 immunostimulatory monoclonal antibody targeted against signaling lymphocytic activation molecule F7 (SLAMF7, also called CS1 [cell-surface glycoprotein CD2 subset 1]), a glycoprotein expressed on myeloma and natural killer cells but not on normal tissues that enables selective killing of myeloma cells with minimal effects on healthy tissue. The SLAM family is a subgroup of the immunoglobulin superfamily of receptors and consists of six members (SLAM, 2B4, Ly-9, NTB-A, CD94, and SLAMF7), all located on chromosome 1q23. More than 95% of bone marrow myeloma cells express SLAMF7 in a manner that is independent of cytogenetic abnormalities. Elotuzumab exerts a dual effect by directly activating natural killer cells and mediating antibody-dependent cell-mediated cytotoxicity through the CD16 pathway.

SLAMF7 mediates activating signals in natural killer cells by coupling with its adapter protein EAT-2. In myeloma cells, SLAMF7 signaling is compromised owing in part to the lack of EAT-2 expression; therefore, elotuzumab does not induce the proliferation of myeloma cells.