Clinical impact of serum soluble SLAMF7 in multiple myeloma

// Mariko Ishibashi 1, 2 , Saori Soeda 1 , Makoto Sasaki 3 , Hiroshi Handa 4 , Yoichi Imai 5 , Norina Tanaka 6 , Sakae Tanosaki 7 , Shigeki Ito 8 , Takeshi Odajima 9 , Hiroki Sugimori 10 , Toshio Asayama 1 , Mika Sunakawa 1 , Yuta Kaito 1 , Ryosuke Kinoshita 1 , Yasuko Kuribayashi 1 , Asaka Onodera 1 , Keiichi Moriya 1 , Junji Tanaka 6 , Yutaka Tsukune 3 , Norio Komatsu 3 , Koiti Inokuchi 1 and Hideto Tamura 1 1 Department of Hematology, Nippon Medical School, Tokyo, Japan 2 Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan 3 Division of Hematology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan 4 Department of Hematology, Gunma University, Gunma, Japan 5 Department of Hematology and Oncology, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan 6 Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan 7 Department of Hematology, The Fraternity Memorial Hospital, Tokyo, Japan 8 Department of Clinical Oncology, Iwate Medical University School of Medicine, Iwate, Japan 9 Faculty of Health Science, Daito Bunka University Graduate School of Sports and Health Science, Tokyo, Japan 10 Department of Preventive Medicine, Daito Bunka University Graduate School of Sports and Health Science, Saitama, Japan Correspondence to: Hideto Tamura, email: tam@nms.ac.jp Keywords: multiple myeloma; SLAMF7; soluble form; CS1; elotuzumab Received: May 17, 2018     Accepted: September 17, 2018     Published: October 05, 2018 ABSTRACT The signaling lymphocytic activation molecule family (SLAMF7; also known as CS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) as well 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 soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patients. In responders to MM therapy, the levels of sSLAMF7 were undetectable or decreased compared with those before treatment. In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein. Thus, our findings suggest that high concentrations of sSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab, may be a useful indicator of disease progression in MM patients.