Serum B‐cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival

Abstract

Summary Although TNFRSF17 (also designated as B‐cell maturation antigen (BCMA)) is expressed on tumour cells in B‐cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age‐matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.

A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

“…13,14 BCMA is expressed on MM cell lines and malignant plasma cells with high prevalence and increased expression levels during disease progression from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma to active MM. [15][16][17][18][19][20][21] BCMA is also expressed on plasmacytoid dendritic cells, which promote MM cell growth, survival and drug resistance. [21][22][23] Expression levels on plasmacytoid dendritic cells are also elevated in MM patients versus normal donors.…”

Soluble B-Cell Maturation Antigen Mediates Tumor-Induced Immune Deficiency in Multiple Myeloma

“…We showed that levels were higher among patients with progressive disease (PD) than those with responsive disease and decreased with response to therapy (17). BAFF stimulates normal mouse and human B-cell proliferation, and addition of recombinant human BCMA-Fc (rhBCMA-Fc) abrogates this effect in vitro (18)(19)(20).…”

“…Four-week-old male CB17 SCID mice were implanted with human multiple myeloma tumors (LAGk-2, LAGk-1A, or LAGl-1) developed from multiple myeloma patients as previously described (17). Tumors were measured and the formula for an ellipsoid volume was applied [4/3 p x (width/2) 2 x (length/2)].…”

“…We recently identified soluble BCMA in serum from multiple myeloma patients (17). We showed that levels were higher among patients with progressive disease (PD) than those with responsive disease and decreased with response to therapy (17).…”

Targeting B-Cell Maturation Antigen in Multiple Myeloma

“…Unlike BAFF, which also binds BAFF-R besides BCMA and TACI, APRIL binds to BCMA and TACI associated with heparan sulfate proteoglycan (HSPG), that is, CD138/syndecan-1 (Figure 1), suggesting a more PC-specific role of APRIL than BAFF [31]. In addition, serum BCMA is Targeting B-cell maturation antigen in multiple myeloma Review higher in MM patients versus healthy donors, suggesting a new biomarker for monitoring disease status and overall survival of MM patients [32]. All these results indicate an important role for the BCMA/APRIL signaling cascade in the pathophysiology of MM.…”