Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients

A Visram,A Dispenzieri,R A Kyle,T M Spektor,S Bujarski,C Soof,J R Berenson,S K Kumar,S V Rajkumar

doi:10.1038/s41408-021-00505-4

Abstract

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07–5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45–2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.

Highlights

The B cell maturation antigen (BCMA), a member of the tumor necrosis factor superfamily, promotes survival and proliferation of plasma cells through signal transduction of the B cell activating factor (BAFF/BLys) and a proliferation inducing ligand [1,2,3]
There was a modest correlation between the baseline bone marrow plasma cell burden and serum BCMA (sBCMA) level (Spearman’s ρ = 0.631, p < 0.001) among 82 monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) patients with both a diagnostic bone marrow biopsy and sBCMA tested on a serum sample collected within 1 month of diagnosis.)
A poor correlation was detected between the sBCMA and quantitative immunoglobulin of the involved heavy chain within 1 month of diagnosis (n = 84 MGUS and SMM patients, Spearman’s ρ = 0.398, p < 0.001) and between the initial sBCMA level and monoclonal protein (MCP) (Spearman’s ρ = 0.462, p < 0.001) or difference in the involved and uninvolved FLC (dFLC) (Spearman’s ρ = 0.383, p < 0.001)

Summary

Introduction

The B cell maturation antigen (BCMA), a member of the tumor necrosis factor superfamily, promotes survival and proliferation of plasma cells through signal transduction of the B cell activating factor (BAFF/BLys) and a proliferation inducing ligand [1,2,3]. Previous work has shown that while serum BCMA (sBCMA) level is present in healthy donors, the levels are higher among those with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and MM [8, 9]. Among patients with MM, increased sBCMA levels correlate with an increased neoplastic plasma cell burden in the bone marrow, as sBCMA levels decrease with response to therapy [9]. In patients with non-secretory MM, where disease monitoring is a challenge due to the absence of circulating monoclonal proteins, sBCMA levels correlated with disease activity based on positron emission tomography (PET) imaging and bone marrow findings [9]. The relative differences in sBCMA levels between MGUS and SMM patients, and the association between baseline levels of sBCMA and risk of progression to MM have not been assessed in these patient populations

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