Elevated serum levels of soluble B-cell maturation antigen as a prognostic biomarker for multiple myeloma

Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical use. Here, we used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome, and MM. Serum BCMA levels were elevated 16.1-fold in patients with newly diagnosed MM compared to healthy donors and rare PC diseases patients. Specifically, the sBCMA levels in patients with progressive disease were 64.6-fold higher than those who showed partial response or above to treatment. The sBCMA level also correlated negatively with the response depth of MM patients. In newly diagnosed and relapsed MM patients, survival was significantly longer among those subjects whose sBCMA levels are below the median levels compared with those above the median value. We optimized the accuracy of the survival prediction further by integrating sBCMA level into the Second Revised International Staging System (R2-ISS). Our findings provide evidence that the novel chemiluminescence method is sensitive and practical for measuring sBCMA levels in clinical samples and confirm that sBCMA might serve as an independent prognostic biomarker for MM. Chemiluminescence method was first established to measure serum BCMA and proved to be sensitive and practical for in clinical samples. Serum BCMA is an important parameter for treatment efficacy evaluation and prognosis prediction in MM, especially in some special subpopulations, such as non-secretory MM, IgD-MM, and patients with BCMA-CAR-T therapy. The accuracy of the survival prediction of MM was further optimized by integrating sBCMA level into the R2-ISS. Graphical Abstract