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Key to MGUS and myeloma may lie in Iceland



In a 12-year-old study, MGUS had a 3% prevalence in the general U.S. population older than age 50 years, and a greater than 5% prevalence after age 70. However, Dr. Mikhael thinks that more refined testing will show the true figure to be close to 10%. Thus, the great majority of patients with MGUS will never develop multiple myeloma.

Pending the potentially practice-changing outcome of iStopMM, Dr. Mikhael said SPE shouldn’t be ordered routinely in an asymptomatic patient, even one with a positive family history for multiple myeloma. The annual cost of monitoring the roughly 540,000 U.S. patients who now carry a diagnosis of MGUS – typically established as an incidental finding by primary care physicians while doing a work-up for another reason – is at least $110 million. And there’s no point in adding to that burden until the benefit of mass screening has been established.

An SPE is appropriate, however, in an older patient with unexplained anemia, known low immunoglobulin levels, unexplained renal insufficiency or neuropathy, or osteopenia or osteoporosis inconsistent with the patient’s age or gender – provided the patient doesn’t have a coexisting plasma cell dyscrasia or B-cell lymphoproliferative disorder, which would throw off the prognostic value of the test results, he continued.

When ordering an SPE to rule in/out MGUS, it’s essential to also order serum free light-chain testing, because it provides key prognostic information.

A landmark study led by investigators at the Mayo Clinic demonstrated that the risk of progression of MGUS to multiple myeloma or a related disorder is independently predicted by three key factors: a high serum M-protein spike of 15 g/L or more on the SPE; the presence of non-IgG MGUS; and an abnormal serum free light-chain ratio of less than 0.26 or more than 1.65. In this study, the 20-year risk of malignant transformation of MGUS ranged from 58% if all three risk factors were present, to just 5% if none were (Blood. 2005 Aug 1;106[3]:812-7).

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