Shorter overall survival among patients with monoclonal gammopathy of undetermined significance

1. Patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) and followed for multiple decades showed shorter overall survival rates compared to matched controls.

2. Risk of progression to multiple myeloma or another blood cell disorder was associated with identified adverse risk factors.

Evidence Rating: 1 (Excellent)

Study Rundown: MGUS is a relatively common condition occurring in over 3% of persons age 50 or older which predisposes patients to increased risk of malignant plasma cell transformation. Prior studies have followed patients for less than 10 years, providing information regarding risks of malignant transformation. Data from longer follow-up is desired as the condition can be slowly progressive and have subtypes with different manifestations. This study follows a large group of MGUS patients for a median of 34.1 years. The primary endpoint of progression to multiple myeloma or plasma-cell or lymphoid disorders was increased compared to a control population, with risk of progression increasing as time with the condition increased. Adverse risk factors were identified which were associated with increased risk of progression. The IgM subtype of MGUS displayed an increased risk of progression compared to the non-IgM MGUS subtype. Overall survival was decreased in MGUS patients compared to matched controls.

This study provides improved natural history data on the progression of MGUS. Its strengths include large size and validation of adverse risk factors associated with disease progression, and a notable feature is the patient population was highly homogeneous.

Click to read the study, published in NEJM

Relevant Reading: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies

In-Depth [prospective cohort]: This prospective cohort study followed 1384 patients for a total of 14 130 person-years from Minnesota diagnosed with MGUS at the Mayo Clinic between 1960 and 1994. Diagnostic criteria included a serum M protein level of 3 grams per deciliter or less and 10% or fewer plasma cells in bone marrow. Patients with light-chain MGUS were excluded. Follow-up consisted of Mayo medical records review and death certificate analysis. The primary endpoint was rate of progression to multiple myeloma or plasma-cell or lymphoid disorders in IgM (n = 210) and non-IgM (n = 1129) subtypes. Analysis of various prognostic factors associated with risk of progression was performed, as well as assessment of overall survival.

During the median of 34.1 years of follow-up 94% of patients passed away. Disease progression occurred in 11% of patients, at a risk 6.5 times higher than a matched cohort (95% confidence interval [CI], 5.5 to 7.7). Risk of disease progression was higher in the IgM (relative risk [RR], 10.8; 95% CI, 7.5 to 15.0) compared to non-IgM subtype (RR, 5.7; 95% CI, 4.7 to 6.9). Risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Initial concentration of serum M protein and serum free light-chain ratio were adverse risk factors associated with risk of progression. At 40 years, risk of death related to plasma- cell disorders was 11%. Compared to a matched cohort MGUS patients had a shorter median survival time (8.1 vs 12.4 years, p < 0.001).

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