Risk of Multiple Myeloma in People with MGUS Can Rise Over Time, Study Finds

People with monoclonal gammopathy of undetermined significance (MGUS) placed at low- or intermediate-risk of progression to multiple myeloma can develop that cancer within five years, a study of blood serum immune markers reports.

This finding warrants annual blood testing for these people, researchers wrote in the study “Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma,” published in the journal JAMA Oncology.

Multiple myeloma is one of only a few cancers that has a defined precursor condition: MGUS, which can be detected in blood tests, but isn’t considered malignant.

Historically, people diagnosed with MGUS are classified as high, intermediate, or low risk. Individuals with high-risk MGUS are considered viable candidates for treatments that may prevent progression, whereas those with low or intermediate risk are typically given standard care by their primary care physicians.

The problem with this classification, an editorial published alongside the study explained, is that it “presupposes that the risk factors remain stable over the life of the disease.”

In other words, because pre-cancerous cells are continuously dividing and changing, a person’s risk of progression to multiple myeloma may change over time — but patients with MGUS are often given a risk score based on a single measurement at one point in time, and that score can hold for years.

Researchers looked at data for 685 people diagnosed with MGUS (67% male, average age 69.1). For each individual, the researchers analyzed all available blood samples (i.e., those taken at multiple time points), totaling 3,266 samples. Data showed 187 people progressed from MGUS to multiple myeloma.

The analysis identified a number of overall risk factors for progression to multiple myeloma, including having the immunoglobulin A isotype, having an abnormal (less than 0.1 or more than 10) serum free light chains ratio, a spike in blood monoclonal protein levels of 15 g/L or more, and immunoparesis, which is defined as the suppression of two or more uninvolved immunoglobulins.

Of note, immunoglobulins are the proteins that form antibodies; in MGUS, cells typically make one particular kind, referred to as an isotype.

In an analysis of 43 people with progression for whom multiple samples over time were available, 23 (53%) were classified as having high-risk MGUS immediately before a cancer finding. Sixteen (70%) of these 23 had been diagnosed with low- or intermediate-risk MGUS, which converted to high-risk MGUS within five years of the myeloma diagnosis.

Similar results were found in analyses focused on light-chain MGUS, a subtype of MGUS.

Importantly, about 60% patients with MGUS progression met the criteria for multiple myeloma up to five years before their diagnosis, supporting “annual blood testing and risk assessment for all individuals with MGUS or light-chain MGUS,” researchers wrote in their study.

“This study … provides an important and biologically relevant concept that risk features are not stagnant, and that patients with MGUS may evolve over time,” the authors of the editorial wrote.

“If this scenario is to be confirmed in additional studies, it would require rethinking of our strategy to follow these patients as well as development of strategies to prevent progression not only in high-risk patients but also in patients at intermediate to low risk of progression,” they added.