Patients with particular abnormal proteins in their blood — a condition known as monoclonal gammopathies of undetermined significance (MGUS) — have a small, but persistent lifetime risk of multiple myeloma or other hematologic cancers.

For more than 40 years, researchers have aimed to define that risk and to identify the patients most likely to progress to active malignancy. Still unresolved, however, is whether to screen the general population for MGUS, a largely asymptomatic condition usually noted during routine blood testing.

Much of what is known about these aberrant plasma proteins comes from a large observational study conducted by researchers at the Mayo Clinic in Rochester, Minnesota. The investigators followed 1384 patients with MGUS in southeastern Minnesota who progressed to multiple myeloma or another plasma disorder between 1960 and 1994. The mean follow-up was slightly over 34 years.

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Results of the longitudinal study — recently updated and expanded — were published in The New England Journal of Medicine earlier this year.1

Although most patients died of other diseases, 11% progressed to multiple myeloma or a related cancer. Overall, the risk of progression was 1% each year, though the risk never dissipated with time. And, patients with MGUS had a shorter survival than those without these proteins in their blood — an unexpected finding requiring further study, the researchers said.

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“This is a bird’s eye view of what’s happening,” said the Mayo Clinic’s Robert Kyle, MD, the study’s principal investigator who first described the term “MGUS” in 1978. Since then, all 3 major immunoglobulins — IgG, IgA and IgM — have been well-characterized, he said, as have 2 other immunoglobulins with fractional percentages in the blood.

Although MGUS is seldom viewed as having “undetermined significance” today, Dr Kyle does not recommend screening in the general population. “If you have MGUS, there’s an almost 90% chance you’ll die of something else — a heart attack, a stroke, or even another malignancy, such as colon cancer,” he said.

MGUS occurs in an estimated 3% of the general population over age 50, rising to 5% or more after age 70. On average, MGUS is first recognized in patients at ages 70 to 72, according to Dr Kyle.

Other than age, MGUS likely has a genetic element, Dr Kyle said, given that patients whose first-degree relatives have multiple myeloma are twice as likely to have MGUS themselves. Race, too, appears to play a role, as MGUS is twice as common in African Americans as it is in the white population, he said.

In the Mayo study, the investigators looked at 2 major types of MGUS — IgM and non-IgM — each showing a distinct pattern of disease and the risk for progression. Patients with IgM had a higher risk of progressing to lymphoma or Waldenstrom macroglobulinemia, while those with non-IgM (defined as IgG and IgA) more often progressed to multiple myeloma.