From Pages to Practice

By James Yeh, M.D., M.P.H.

Published January 5, 2022


Monoclonal gammopathy, defined by the presence of an M-spike on serum protein electrophoresis (SPEP), is a spectrum of plasma cell dyscrasias ranging from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.

The amount of circulating monoclonal protein, the presence of clinical symptoms, and the portion of plasma cells in the bone marrow biopsy help differentiate the various conditions within the spectrum of monoclonal gammopathy.

MGUS is defined as the presence of an M-spike with a concentration <3g/dL, <10% plasma cells on bone marrow biopsy, and the absence of the so-called “CRAB” symptoms of multiple myeloma (hypercalcemia, renal insufficiency, anemia and bone lesions).

What is this study about?

In this cohort study, 1384 patients from Minnesota in whom MGUS was diagnosed at the Mayo Clinic from 1960 through 1994 were followed until December 31, 2015 (median follow-up, 34 years; range 0–43 years)

The primary outcome was the progression from MGUS to multiple myeloma or to another plasma or lymphoid malignancy. The investigators also determined the effect of adverse risk factors (demographic and laboratory information) at the time of diagnosis on the risk of progression.

What are the results?

During 14,130 person-years of follow-up, 94% of patients died. MGUS progressed in 11% (147 patients).

The relative risk of progression was 6.5-fold higher than in the general population (95% CI 5.5–7.7). The risk of progression from MGUS to multiple myeloma or to another plasma or lymphoid malignancy (not accounting for death due to competing causes) was 10% at 10 years, 18% at 20 years, 28% at 30 years, 37% at 35 years, and 37% at 40 years.

IgM MGUS was associated with a greater risk of progression than non-IgM MGUS (relative risk, 10.8 vs. 5.7). Two adverse risk factors, an abnormal serum free light-chain ratio (ratio of kappa to lambda free-light chains) and a high serum M protein level (³1.5 g/dL), were associated with risk of progression. The risk of progression was highest in those with both risk factors. In patients with IgM MGUS, the risk of progression at 20 years was 55% (those with 2 risk factors), 41% (1 risk factor), and 19% (neither). Corresponding rates in patients with non-IgM MGUS were 30%, 20%, and 7%.

Patients with MGUS had shorter survival than the control population matched for age and sex (median, 8.1 vs. 12.4 years; P<0.001).

What is my take-away?

MGUS progression occurred in 11% of patients — a rate that was 6.5-fold higher than in the general population. The type of MGUS (IgM or non-IgM) was associated with different risks of progression and the presence of adverse risk factors (such as serum free light-chain ratio and higher M protein levels) provide prognostic information.

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James Yeh, MD MPH, Physician at NEJM Group
James Yeh, MD MPH, Physician at NEJM Group
NEJM Knowledge+