Serum Levels of B-Cell Maturation Antigen Are Elevated in Waldenström's Macroglobulinemia Patients and Correlate with Disease Status and Conventional M-Protein and IgM Levels

Background: Waldenström's macroglobulinemia (WM) is an incurable B-cell lymphoplasmacytic lymphoma.  B-cell maturation antigen (BCMA) serves as one of the receptors for B-cell activating factor (BAFF) or a proliferation-inducing ligand (APRIL), which are members of the tumor necrosis factor (TNF) family that can induce activation of NF-κB and promote survival of B cells, including neoplastic B cells.  We previously showed that serum BCMA levels are elevated in multiple myeloma (MM) patients, and correlated with disease status and overall survival (OS). In this study, we sought to determine whether BCMA levels are elevated in the serum of WM patients, track with conventional WM tumor markers, and correlate with disease status and OS.

Methods: Data was obtained on a total of 67 WM patients who received treatment in one of two clinics that specialize in the treatment of WM.  Serum BCMA levels were determined with a polyclonal anti‑BCMA antibody using an ELISA (R&D Systems, Minneapolis, MN). Mann-Whitney analysis was used to measure differences in serum BCMA levels between WM patients and healthy subjects as well as the clinical status of WM patients.  Using Kaplan-Meier analysis, OS (median follow up 5.1 years) in WM patients was measured from the time of the first assessment of serum BCMA levels in each patient. In addition, serum BCMA levels were compared to serum M‑protein and IgM levels in 12 patients, serially, during their individual courses of treatment.   

Results: We compared serum BCMA levels for all 67 patients, including 27 untreated WM patients to healthy subjects (n = 76).  Serum BCMA levels were markedly elevated in all WM patients (median 79.53 ng/mL), including those who were untreated (median 82.72 ng/mL) versus healthy subjects (median 6.32 ng/mL, p < 0.0001 for both comparisons).  Serum BCMA values were compared to both serum M-protein and IgM levels in 12 WM patients during their disease course.  Serum BCMA levels consistently correlated with changes in both of these established WM serum markers during their course of disease.  Serum BCMA levels of WM patients also correlated with patient disease status at the time of sample collection.  Specifically, serum from patients achieving > partial response (PR, n = 12) showed significantly lower levels of BCMA than samples from patients with either stable disease (SD, n = 8, p = 0.030) or progressive disease (PD, n = 21, p = 0.0004). OS (median 12.5 years) was determined among patients in the highest serum BCMA quartile (n=16; quartile range 128.91-812.48 ng/mL) and compared to levels in the lower three quartiles (n = 48; range 20.13-128.85 ng/mL). Notably, OS was shorter among patients in the top quartile compared to those in the other three quartiles (p = 0.02).

Conclusions: This is the first study to demonstrate that serum BCMA levels are elevated in Waldenström’s macroglobulinemia patients.  Importantly, serum BCMA levels correlated with both serum IgM and M‑protein levels, as well as tracked with these established WM biomarkers for individual patients during their course of disease.  Additionally, patients with levels of BCMA in the highest quartile exhibited shorter OS.  Thus, serum BCMA represents a new serum biomarker to predict outcome and monitor patients with Waldenström’s macroglobulinemia.