Monoclonal Gammopathy of Unknown Significance (MGUS): A Mortality Analysis

Objectives.— To assess the mortality risk of patients with monoclonal gammopathy (MGUS), a pre-malignant condition with limited survival data, using 2 distinct mortality analysis methods, and to investigate how the presence or absence of high-risk factors influences survival outcomes among immunoglobulin M (IgM) vs non-IgM MGUS. Methods.— The first method involves a re-analysis of mortality data from the previously published study, “Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance.” 1 This approach applies classic mortality and survival methodologies to calculate excess death rates (EDRs) and mortality ratios (MRs) in a cohort of 1384 MGUS patients identified within a well-defined geographic area and followed for a median duration of 34.1 years. The second method estimates the mortality risk of MGUS patients through a Markov analysis. This approach incorporates data from broader literature, examining the risk of progression from MGUS to multiple myeloma (MM) and the associated risk of death from MM. Results.— First method During 14,130 person-years of follow-up, MGUS progressed to multiple myeloma, lymphoma, and other hematological malignancies in 147 patients (11%), a rate that was 6.5 times higher than the rate of the control population. The overall risk of progression, excluding deaths from competing causes, was 10% at 10 years, 18% at 20 years, and 36% at 40 years, with variations based on monoclonal immunoglobulin type. Patients with MGUS exhibited shorter survival than was expected in the control population of Minnesota, US residents of matched age and sex. Relative mortality calculations have demonstrated a mildly increased mortality risk (ie, average mortality ratio of approximately 150%), with higher mortality ratios after initial diagnosis of MGUS. Second method The annual risk of death for individuals with multiple myeloma (MM) was estimated using geometric average annual mortality ratios derived from a 20-year SEER-17 database survival analysis. Applying an average transition probability of 1% per year for a 60-year-old population of 50% males and considering an average MM mortality ratio of 550%, the MGUS MR was 140% and increased to 170% for a higher probability of 2% per year. Conclusion.— MGUS patients have a lower overall survival rate than the general population (median, 8.1 vs 12.4 years). Survival outcomes are influenced by various prognostic factors, with initial concentration of serum M protein and type and serum free light-chain ratio being the most significant univariate risk factors for progression and mortality.