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 [2–4]. 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. Serum and clinical data were collected from patients enrolled into the Japanese phase 2 clinical CA204-116 study (clinicaltrials. gov identifier: NCT02272803) to evaluate the efficacy and safety of ELd for newly diagnosed MM [10]. The study design and results have been published [10]. A total of 82 Japanese patients were enrolled and randomized into two groups, ELd arm (n= 40) and Ld arm (n= 42). The details of the study, patient and disease state characteristics, patient background, study design, and clinical results were also published previously [10]. Serum was collected before (at Day 1 of Cycle 1 before treatment: baseline) and after (at Day 1 of Cycle 3) treatment and sSLAMF7 was assessed as previously described [8]. Baseline sSLAMF7 was detected in patients in both arms; the median value was 6.9 ng/mL but the level varied widely (0.08–197 ng/mL; Fig. 1 a) consistent with results of the previous study [8]. Patients at several ISS stages (ISS-I: 19; ISS-II: 46; ISS-III: 17) were enrolled in the CA204-116 study [10], and the median level of sSLAMF7 was increased with ISS stage (Fig. 1 b, P= 0.026 by using oneway analysis of variance).

Next we examined an alteration of serum sSLAMF7 levels before and after the treatments. As shown in Fig. 1 c, a decrease in serum sSLAMF7 was observed after treatment in both the ELd (median; 5.6–0.3 ng/mL) and Ld arms (median; 8.0–1.4 ng/mL). These findings are consistent with our previous results, showing that elotuzumab neutralizes sSLAMF7 and that lenalidomide downregulates SLAMF7 transcription [9].