Hypoalbuminemia: a new risk factor for progression in patients with monoclonal gammopathy of uncertain significance

Recent studies have advanced the understanding of the pathogenesis of monoclonal gammopathy of uncertain significance (MGUS), describing the influence of a proinflammatory bone marrow environment on the risk of progression. While albumin is a known inflammatory prognostic biomarker in multiple myeloma, its role in MGUS has not been explored. We conducted a retrospective study to investigate the prognostic value of albumin in MGUS. Eight hundred and thirty-eight patients with MGUS were included: 71 (8.5%) presented hypoalbuminemia (≤3.5 g/dL) at diagnosis. Hypoalbuminemia was more common in men (63.4% vs. 49.3%; P = 0.025), older age (≥70 years: 74.6% vs. 57.2%; P = 0.005), and IgA isotype (33.8% vs. 21.4%; P = 0.018). These patients presented lower hemoglobin levels and higher creatinine values (P < 0.001 and P < 0.001). Serum M protein ≥ 1.5 g/dL (HR 18.9 [95% CI, 1.8-200.8]; P = 0.015) and hypoalbuminemia (HR 14.7 [95% CI, 1.7-124.7]; P = 0.014) were identified as independent prognostic factors for progression. In our series, Mayo Clinic and MGUS-like phenotype models were validated, and the incorporation of hypoalbuminemia into these models helped identify a subgroup of intermediate-risk patients with a higher risk of progression. In conclusion, if confirmed by independent studies, hypoalbuminemia could be integrated into existing prognostic models, improving risk stratification and guiding clinical decision-making.