Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II
Methods: Two enzyme-linked immunosorbent assays were developed to detect sSLAMF7 in the presence of elotuzumab: the total assay (TA) detected all forms of sSLAMF7 (both unbound and elotuzumab-bound sSLAMF7) and the free assay (FA) detected only unbound sSLAMF7. Serum was collected from peripheral blood before initiation of treatment (C1D1) and during treatment (C2D1) and assessed for levels of sSLAMF7 by the TA and FA. Soluble component (non-cellular) from bone marrow aspirates were obtained prior to any therapy to assess the relationship between concentrations of sSLAMF7 in matched marrow and blood samples.
Results: As previously reported, these data confirm sSLAMF7 expression in patients with MM. The TA demonstrated a significant dose- and time-dependent increase in sSLAMF7 following elotuzumab treatment alone or in combination with either bortezomib/dexamethasone (E-B/d) or lenalidomide/dexamethasone (E-L/d); this increase was not observed in patients treated with bortezomib/dexamethasone (B/d) only. The increase in total sSLAMF7 observed in the TA demonstrated elotuzumab pharmacodynamic specificity and likely reflected stabilization of the protein in the serum. The FA detected a significant decrease in free sSLAMF7 (at C2D1) in both elotuzumab- and non–elotuzumab-treated patients, with the greatest reduction observed in elotuzumab-treated patients. The decrease in free sSLAMF7 detected using the FA, regardless of treatment, suggest the potential use of this biomarker as a surrogate for disease burden. Additionally, the extent of the C2D1 changes in free and total sSLAMF7 following elotuzumab-containing regimens demonstrated a trend for association with increased depth of response (comparing progressive disease/stable disease/minimal response vs partial response vs very good partial response/complete response). Baseline and C2D1 levels of serum sSLAMF7 showed a trend for an inverse relationship with progression-free survival (for E-L/d) but this was not statistically significant. Baseline sSLAMF7 did demonstrate a positive relation with the percentage of bone marrow plasma cells. At C2D1, with the dose of 10 mg/kg, the mean elotuzumab concentration was 337.1 µg/mL (N=38; CV of 51.6%), which was significantly higher than the mean free sSLAMF7 concentration 0.255 ng/mL (N=37; CV of 200%). In addition, E-L/d treatment demonstrated the greatest reduction of free sSLAMF7 (more than 80% of patients treated with E-L/d reached >75% of free sSLAMF7 reduction) compared with that observed for E-B/d and B/d.
Conclusions: Together, these data suggest that sSLAMF7 may be a surrogate marker of disease burden in MM, and early changes in sSLAMF7 may provide an indication of likelihood of response. Additional analysis of sSLAMF7 is ongoing and future studies will help us to further understand the use of this biomarker for prognostic or predictive purposes.
Study supported by: Bristol-Myers Squibb
Disclosures: Postelnek: Bristol-Myers Squibb: Employment . Off Label Use: Elotuzumab is an investigational agent being studied for the treatment of multiple myeloma.. Sheridan: AbbVie Biotherapeutics: Employment , Equity Ownership . Keller: AbbVie Biotherapeutics: Employment , Equity Ownership . Sheng: Bristol-Myers Squibb: Employment , Equity Ownership . Poulart: Bristol-Myers Squibb: Employment . Robbins: Bristol-Myers Squibb: Employment , Other: shareholder .
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