Early Soluble B-Cell Maturation Antigen (BCMA/TNFRSF17) Kinetics as a Molecular Biomarker of Treatment Response in Multiple Myeloma Patients.

Soluble B-cell maturation antigen (sBCMA), generated by shedding of the plasma-cell receptor BCMA/TNFRSF17, is a circulating marker of plasma-cell burden in multiple myeloma (MM). We investigated whether early sBCMA kinetics capture treatment-induced changes in disease biology and predict subsequent Quality of Response (QoR) beyond free light chain (FLC)-based measures. In this prospective longitudinal study, 100 patients with newly diagnosed or relapsed MM starting treatment were evaluated at baseline, 1 month, and 6 months. sBCMA, involved FLC (iFLC), and involved-to-uninvolved FLC ratio (rFLC) were measured, and a 6-month response was assigned according to International Myeloma Working Group criteria. All biomarkers decreased significantly after treatment initiation (p < 0.0001). Across disease-status cohorts, sBCMA, but not iFLC or rFLC, differed at baseline and showed significantly different 1-month percentage reductions. Larger early decreases in sBCMA, iFLC, and rFLC were associated with deeper 6-month responses. In ordinal logistic regression including the three biomarkers dichotomized by a 50% reduction threshold at 1 month, only sBCMA remained independently associated with QoR; patients with <50% sBCMA reduction had higher odds of worse 6-month response (OR 5.44, 95% CI 1.58-18.76; p = 0.007). These findings support early sBCMA kinetics as a biologically informative marker for short-term response monitoring in MM.