Clinical impact of serum soluble SLAMF7 in multiple myeloma

Abstract

The signaling lymphocytic activation molecule family (SLAMF7 also known asCS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) aswell as natural killer (NK) cells and is a well-known therapeutic target of elotuzumab.The objective of this study was to evaluate the clinical significance of serum solubleSLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impactof sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percentof MM patients, but not patients with monoclonal gammopathy of undeterminedsignificance and healthy controls, had detectable levels of serum sSLAMF7, whichwere significantly increased in advanced MM patients. Further, MM in sSLAMF7-postivepatients exhibited aggressive clinical characteristics with shorter progression-freesurvival times in comparison with sSLAMF7-negative patients. In responders toMM therapy, the levels of sSLAMF7 were undetectable or decreased compared withthose before treatment. In addition, the anti-SLAMF7 antibody-mediated antibodydependent cellular cytotoxicity of NK cells against MM cell lines was inhibited byrecombinant SLAMF7 protein. Thus, our findings suggest that high concentrations ofsSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab,may be a useful indicator of disease progression in MM patients.