Professor Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece Athens, Attiki, Greece
Introduction: Serum B-cell maturation antigen (sBCMA) levels have emerged as potential biomarkers for disease monitoring with prognostic value in patients with multiple myeloma (MM).
Methods: We evaluated sBCMA distribution with Elecsys® sBCMA assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) and its potential prognostic role in patients with MM and smoldering MM (sMM) by a single institution. Patients with sBCMA values outside of measuring range (1.2-900 ng/mL) were excluded.
Results: 166 patients diagnosed from 2018 to 2020 were included (median follow up: 38 months). The median age was 67 years (range 50-93 years), 101 (61%) were males, 122 had symptomatic MM and 44 had SMM. The baseline mean sBCMA value was 162 ng/mL (SD 169) for patients with MM and 19.4 ng/mL (SD 16.5) for SMM. In a subset of patients with MM, there were available data at the time of first (n=68) and second (n=20) disease progression. At first disease progression, the mean sBCMA value was 102 ng/mL (SD 148), whereas at second disease progression the mean sBCMA value was 169 ng/mL (SD 275). There was a general trend towards decreasing sBCMA values from baseline to first disease progression (mean difference -82.9ng/mL, 95%CI: -118 to -47.8ng/mL, p< 0.0001). In general, the results were consistent among the risk stratification subgroups based on ISS staging. The sample size was rather small for the second disease progression timepoint (the estimated mean difference of 56.1% which corresponds to a 43.9% decrease from baseline, p = 0.028). The baseline mean sBCMA value was lower in patients without documented disease progression (103 ng/mL, SD 107) compared with patients who had one (200 ng/mL, SD 194) or two (198 ng/mL, SD 185) disease progressions during the follow-up period. In addition, there was no meaningful association between sBCMA baseline values and best response during first line treatment. Furthermore, patients with symptomatic MM were categorized as low (n=61) or high expressors (n=61) based on sBCMA expression at baseline; low expressors had baseline sBCMA values below 113 ng/mL (median) and high expressors had baseline sBCMA values ≥ 113 ng/mL. The median progression-free survival (PFS) was 24.7 months (95%CI: 20.1 to 32.4) for high expressors and 53.7 months (95%CI: 26.9 to not reached) for low expressors (HR 1.67, log-rank p=0.031). In the subgroup analysis according to ISS, a significant association became evident only for patients with ISS 3 (HR 2.24, 95%CI: 1.12 to 4.48, p=0.023, high versus low expressors). Interestingly, high expressors had a median OS of 58.4 months (95%CI: 46 to not reached) compared with low expressors (median OS not reached, HR 2.05, log-rank p = 0.039).
Conclusions: MM patients with high baseline sBCMA levels seem to have a dismal prognosis compared to those with low sBCMA levels. Sequential evaluation of sBCMA in prospective studies will determine the value of incorporating sBCMA measurement in the clinical practice.