Research Scientist The University of Texas MD Anderson Cancer Center Houston, Texas, United States
Introduction: Current evidence from retrospective studies supports serum(s)BCMA as a novel biomarker in the diagnosis, prognosis, response and surveillance in myeloma precursor disease (MPD): monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Independent prospective validation of sBCMA is essential. We analyzed prospectively collected serum samples of MPD patients enrolled on clinical studies.
Methods: A total of 730 samples belonging to 187 patients were included in the study [624 samples from 150 patients in ORIGIN (Observational prospective Research study In monoclonal Gammopathies leading to myeloma NCT02726750); 26 samples from 13 patients with int. and high-risk SMM treated with pembrolizumab (NCT02603887) and 80 samples from 24 high-risk SMM patients in ISAMAR treated with isatuximab (ISA) (NCT02960555)]. sBCMA levels were measured in triplicate by enzyme-linked immunosorbent assay (ELISA) with human anti-BCMA/TNFRSF17 antibody from R&D systems (catalogue# DY193). SPSSv20 was used for statistical analysis, Mann-Whitney and ANOVA tests were used for non-parametric and parametric comparisons, respectively.
Results: In ORIGIN, where untreated MGUS and/or SMM patients are followed prospectively until progression, the baseline sBCMA was significantly lower in MGUS vs SMM patients, [44.4 (IQR20.2-67.5) vs 59.4 (IQR34.3-120.8) ng/mL; p=0.006]. Longitudinal analysis showed that MGUS progressors (to SMM) (n=4) and SMM progressors (to MM) (n=13) had increasing sBCMA over time. The median sBCMA level at baseline, 1, and 3 years was 62.7 (IQR32.3 – 257.4), 81.3 (IQR27.9 – 239.2), and 139.5 (IQR123.9 – 139.5) ng/mL in MGUS-> SMM and 11.6 (2.6 – 45), 14.7 (4.3 – 61.3) and 27.8 (9.2 – 80.1) ng/mL in SMM->MM patients. MGUS patients (n=4) that progressed to SMM had a higher baseline sBCMA compared to non-progressor MGUS (n=54) [62.8 (IQR32.3 – 257.4) vs 43.3 (IQR15.7 – 64.3) ng/mL; p=0.236]. SMM patients who were treated with either pembrolizumab or ISA monotherapy on protocol and did not progress to MM (n=30) had lower baseline sBCMA compared to SMM progressors (n=7) (82.3 (IQR62.3 – 148.4) vs 176 (IQR101.7 – 330.7) ng/mL, p=0.078. In ISAMAR, sBCMA significantly decreased after treatment with ISA [baseline sBCMA 101.5 (IQR70.9 – 181.3)), after 30 cycles 14.9 (IQR9.3 – 69.3) ng/mL (p < 0.001)]. Correlation analysis of the serum paraprotein, i:u sFLC ratio and sBCMA throughout treatment showed significant reduction in all 3 parameters, but the slope of sBCMA decrease after treatment was significantly more pronounced than in the ratio or paraprotein (p < 0.001).
Conclusions: sBCMA can be used for prediction of progression in MPD, where it may be an independent biomarker. Additionally, it may be used in response monitoring in MPD treatment allowing for faster assessment of response compared to traditional blood markers.
