Serum Levels of B-Cell Maturation Antigen Are Elevated in Multiple Myeloma Patients and Correlate with Disease Status and Overall Survival

Abstract

Abstract 4026 Background:B cell maturation antigen (BCMA) is a receptor whose expression increases during B-cell development and is found on malignant cells from multiple myeloma (MM) patients; however, it has not been identified in human serum. Methods:Following informed consent (Western IRB BIO 001), serum was isolated from MM patients and analyzed with a BCMA enzyme-linked immunosorbent assay. Values represent the mean of triplicate experiments. Our human MM xenograft (LAGκ-2) was grown in SCID mice, and animals were treated with bortezomib (BORT) and cyclophosphamide (CY); tumor volume and BCMA levels were determined. Statistical significance of differences observed was determined using a Student's t test and analysis was determined using GraphPad prism software. Results:The serum BCMA levels from newly diagnosed MM patients (n = 58) was much higher (13.26 ng/ml) than among age-matched healthy subjects (n = 45; median 2.57 ng/ml; P < 0.0001) and MGUS subjects (n = 25; median 4.43 ng/ml; P = 0.002). Notably, protein levels were much higher among patients with relapsed or refractory disease (n = 88; median 18.99 ng/ml) compared to those with responsive (> partial response) disease (n = 95; median 3.48 ng/ml; P = 0.0016). Following treatment, patients with responsive disease showed decreases in BCMA levels whereas those with progressive disease showed increases. Additionally, with a median follow-up of 8 months (range, < 0 – 83 months), MM patients (n = 193) with BCMA levels above the median (8.43 ng/ml) showed a shortened survival compared to those with amounts below the median concentration (P < 0.0001). Following treatment with BORT and CY, we also showed a marked decrease in tumor volume and serum human BCMA levels in mice bearing the MM LAGκ-2 xenograft whereas untreated animals showed marked increases in tumor size and serum BCMA. Conclusions:This is the first report identifying serum BCMA in any human disease and suggests that these levels may be a novel biomarker for monitoring disease status and therapeutic response in MM patients. Disclosures:No relevant conflicts of interest to declare.