Pre-diagnostic serum immune marker levels and multiple myeloma: A prospective longitudinal study using samples from the Janus Serum Bank in Norway.

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Only a minority of MGUS patients will develop MM, but precise prediction of progression is impossible using routine clinical biomarkers. Changes in the levels of blood immune markers can help predict disease progression. Data remain inconsistent for some markers of interest such as monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1α), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), fractalkine, and transforming growth factor-alpha (TGF-α). We aimed to investigate the associations between the pre-diagnostic serum levels of these candidate biomarkers and future MM risk, as well as to assess marker changes over time. We performed a nested case-control study using prospective samples from the Janus Serum Bank in Norway to investigate associations between MM risk and pre-diagnostic serum levels of MCP-3, MIP-1α, FGF-2, VEGF, fractalkine, and TGF-α. The study included 293 future MM cases with serum samples collected 20 years (median) before MM diagnosis and 293 matched cancer-free controls. MM patients had an additional pre-diagnostic sample collected up to 42 years before diagnosis to identify marker changes over time. Markers with >60% detection rate (MIP-1α, VEGF, and TGF-α) were included in the statistical analysis. We observed no statistically significant associations between MM risk and serum levels of MIP-1α, VEGF, or TGF-α in samples collected 20 years before diagnosis. However, TGF-α levels decreased significantly closer to the diagnosis in MM patients (p<0.001). The decrease in TGF-α levels may reflect subtle microenvironmental changes related to MM progression.