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.
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.
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.
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.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.