Preexisting plasma cell disorders, such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), are identified in at least one-third of patients with multiple myeloma (MM). This study analyzed prediagnostic sera from 30 patients with MM and found that 90% had a detectable monoclonal immunoglobulin (M-Ig) before diagnosis. A newly recognized entity, light-chain MGUS, was identified in several cases, with all light-chain or nonsecretory myelomas evolving from this condition. Additionally, significant increases in serum free light chain (sFLC) ratios often preceded MM diagnosis, suggesting that sFLC dynamics may serve as an early marker of disease progression.

The findings indicate that MM almost always evolves from premalignant plasma cell disorders, highlighting the need for better biomarkers to predict progression. Current risk stratification models, which classify MGUS and SMM based on factors such as M-Ig levels and sFLC ratios, may be insufficient to refine follow-up strategies. Light-chain MGUS represents a new premalignant condition requiring further investigation. It is noted that future research should explore improved proteomic and genomic markers to enhance early detection and risk assessment in plasma cell disorders.

Reference: Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22):5418-22. doi: 10.1182/blood-2008-12-195008.