Annual Test Best for Monoclonal Gammopathy of Undetermined Significance

By David Douglas

July 25, 2019

NEW YORK (Reuters Health) - The risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma appears to be inconsistent, prompting a need for annual testing, according to researchers.

"The results from this prospective screening study help us to better understand the previously reported annual risk of 0.5% to 1%, which is reflective of the average risk," Dr. Ola Landgren of Memorial Sloan Kettering Cancer Center, in New York City, told Reuters Health by email. "In the current study we show how the risk varies greatly for individual patients with MGUS."

Dr. Landgren and colleagues used data from participants in the prospective National Cancer Institute Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to identify 685 people with MGUS. They obtained all 3,266 available serially stored prediagnostic serum samples for these patients.

Through 16 years or less of follow-up, 27% of patients had progression from non-IgM MGUS to multiple myeloma and from light-chain MGUS to light-chain multiple myeloma. In the rest, the diagnosis continued to be non-IgM MGUS without progression and light-chain MGUS without progression. All participants were diagnosed between 1993 and 2011, and the data were analyzed in 2018.

In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio, 1.80; P=0.04), a monoclonal spike of 15 g/L or more (aOR, 23.5; P<0.001), a skewed (<0.1 or >10) serum free-light-chain ratio (aOR, 46.4; P<0.001) and severe immunoparesis (aOR, 19.1; P<0.001).

Risk factors associated with progressive light-chain MGUS were skewed serum free-light-chain ratio (aOR, 44.0; P<0.001) and severe immunoparesis (aOR, 48.6; P<0.001), the researchers report in JAMA Oncology, online July 18.

In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 (53%) had high-risk MGUS before progression. Of these, 16 (70%) experienced conversion from low-risk or intermediate-risk MGUS within five years. Similar results were found for light-chain MGUS.

"Our results show that low-risk can develop into high-risk and progress to multiple myeloma," said Dr. Landgren, "The implications are: do annual blood test and reassessment based on updated results."

In an editorial, Dr. Nikhil C. Munshi of Harvard Medical School, in Boston, and colleagues note that the study "provides an important and biologically relevant concept that risk features are not stagnant, and that patients with MGUS may evolve over time with the disease developing more aggressive characteristics prior to proceeding to developing malignant transformation."

"This study," he told Reuters Health by email, "highlights the evolutionary pattern in smoldering myeloma and confirms the need to improve the risk stratification in this disease, that includes genomic and other analysis."


JAMA Oncol 2019.