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Multiple myeloma gammopathies

Soluble SLAMF7 is a predictive biomarker for elotuzumab therapy

Leukemia volume 34, pages 3088–3090 (2020)Cite this article

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Signaling lymphocyte activation molecule family member 7 (SLAMF7) is a type I transmembrane protein expressed on myeloma cells and a subset of immune cells [1]. Based on the unique expression profile of SLAMF7, the monoclonal antibody elotuzumab was developed and is approved for patients with multiple myeloma (MM) in the USA, EU, and Japan [2,3,4]. Elotuzumab exhibits antimyeloma activity in combination with either of the immunomodulating drugs (IMiDs) lenalidomide or pomalidomide, and its mechanism of action (MoA) is thought to promote antibody-dependent cellular cytotoxicity by natural killer (NK) cells and NK cell activation [5, 6]. Despite the MoA, elotuzumab monotherapy did not show enough efficacy in a phase 1 clinical trial; no patients exhibited complete response, very good partial response, or partial response, but 26.5% of patients exhibited stable disease [7], suggesting an additional, NK cell system-independent, MoA for the antimyeloma activity of elotuzumab.

Soluble SLAMF7 (sSLAMF7) has been detected in patients with MM, not in healthy volunteers; however, its pathophysiological role is still unclear [8]. We recently found that sSLAMF7 enhances myeloma proliferation by activating mitogen-activated protein kinase pathway via sSLAMF/SLAMF7 interaction and that elotuzumab suppressed sSLAMF7-induced myeloma growth by neutralization of sSLAMF7 [9]. Interestingly, IMiD downregulated transcription of SLAMF7 gene that is regulated by IKZF1/3 [9]. Thus, elotuzumab and IMiD combination suppresses myeloma progression by suppressing sSLAMF7 through dual ways [9]. Here, we focused on the clinical impact of elotuzumab and sSLAMF7 level in patients with MM by analyzing serum sSLAMF7 from clinical trial.

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Fig. 1: Potential of sSLAMF7 as a predictive biomarker for multiple myeloma and elotuzumab treatment.

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Acknowledgements

This study was funded by Bristol-Myers Squibb K.K. English editing and formatting for journal submission was supported by Caudex, funded by Bristol-Myers Squibb K.K.

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  1. These authors contributed equally: Atsushi Suzuki, Satoshi Kakugawa, Masafumi Miyoshi

Authors and Affiliations

  1. Bristol-Myers Squibb K.K., Shinjuku, Tokyo, Japan

    Atsushi Suzuki, Satoshi Kakugawa & Masafumi Miyoshi

  2. Department of Hematology, Ibaraki Prefectural Central Hospital, Kasama, Japan

    Mitsuo Hori

  3. Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

    Kenshi Suzuki

  4. Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan

    Yusuke Furukawa

  5. Hematology Ohta Clinic, Shinsaibashi, Osaka, Japan

    Kensuke Ohta

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Contributions

AS prepared manuscript; AS, SK, and MM collected and analyzed data from CA204-116 study; MH, KS, and KO contributed CA204-116 study execution and data analysis, and YF supported and directed sSLAMF7 analysis.

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Correspondence to Atsushi Suzuki.

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Conflict of interest

AS, SK, and MM are employees of Bristol-Myers Squibb K.K. MH reports postmarketing surveillance study fees from Celgene, Fujifilm RI Pharma, and Shire Japan. KS reports personal fees from Bristol-Myers Squibb K.K., Celgene, Janssen Pharmaceutical, Novartis, Sanofi, and Takeda. YF is supported by Grant-in-Aid for Scientific Research from JSPS, Ministry of Education, Culture, Sports, Science and Technology-supported program for the Strategic Foundation at Private Universities, Japan Leukemia Research Fund, Yasuda Memorial Cancer Foundation, Novartis Foundation, and Takeda Foundation. KO reports honoraria from Bristol-Myers Squibb K.K., Celgene K.K., Janssen Pharmaceutical K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd, and Takeda Pharmaceutical Co. Ltd.

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Suzuki, A., Kakugawa, S., Miyoshi, M. et al. Soluble SLAMF7 is a predictive biomarker for elotuzumab therapy. Leukemia 34, 3088–3090 (2020). https://doi.org/10.1038/s41375-020-0860-7

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