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Mass Spectrometry-Detected MGUS May Have Modifiable Risk Factors

June 6, 2024

July 2024

Khylia Marshall

Khylia Marshall is a freelance journalist based in Tucson, Arizona.

The high sensitivity of mass spectrometry (MS) has contributed to advancements in identifying monoclonal gammopathies of undetermined significance (MGUS), enabling researchers to identify potentially modifiable risk factors for MGUS in high-risk populations, according to a study published in Blood Advances.

Traditional risk factors associated with MGUS, a premalignant condition of multiple myeloma (MM), include older age, male sex, Black race, and family history. In the first nationwide screening study for individuals at high risk for MM to report MS-detected monoclonal gammopathies, David Lee, MD, MPH, MMSc, of Massachusetts General Hospital in Boston, and colleagues evaluated lifestyle risk factors such as body mass index (BMI), physical activity, sleep, and smoking.

“Despite significant advancements in treatment, MM is still considered an incurable disease, and by the time it is diagnosed, many patients are already found to have complications and signs of end-organ damage from the disease. A better understanding of MGUS risk factors may provide opportunities for identifying lifestyle-related prevention strategies for MGUS and MM,” Dr. Lee said.

The study included 2,628 participants who either self-identified as Black and/or had a family history of hematologic malignancy or MM precursor condition. Participants completed an exposure assessment survey, and serum samples were tested using both SPEP/IFX and MALDI-TOF MS assays.

Results showed that an elevated BMI (≥30 kg/m2) was associated with a 73% higher likelihood of MS-MGUS compared to participants with a normal BMI (18.5 to <25 kg/m2; p=0.003).  “While obesity is an established modifiable risk factor for MM, the data have not yet been clear regarding its association with myeloma precursor conditions. Our study contributes one further piece of evidence that obesity may also be associated with MGUS,” Dr. Lee said.

Furthermore, participants who had high levels of physical activity (≥73.5 MET-hours/week) had decreased likelihood of MS-MGUS, compared to those with the lowest levels of physical activity (<10.5 MET-hours/week; p=0.009). This inverse association remained consistent independent of BMI group, smoking pack-years, and alcohol consumption levels, raising “the question of whether lifestyle-related interventions, such as weight loss or exercise, may help prevent the development of MM at earlier premalignant stages,” Dr. Lee said.

Consistent with previous findings, compared with never smoking, heavy smoking (>30 pack-years) was associated with MS-MGUS (p=0.005), possibly attributable to chronic antigenic stimulation caused by heavy smoking.

Additionally, researchers identified an association between MS-MGUS and short sleep (<6 hours/day; p=0.003). This association may result from lower melatonin levels, resulting in decreased antitumorigenic effects and immune system disturbances, and contributing to metabolic system dysregulation associated with obesity.

Overall, MS demonstrated superior sensitivity over SPEP/IFX in identifying a larger pool of M-proteins of at least 0.2 g/L concentration. MS also revealed that the prevalence of MGUS may be two to three times higher than estimated with SPEP/IFX testing. Researchers found risk factors for MGUS did not reach statistical significance with SPEP/IFX, which they tentatively attribute to the lower number of MGUS cases identified by this assay.

Researchers recommend future studies validate these findings to help identify populations that may benefit from enhanced surveillance and targeted screening and precision prevention strategies.

Meanwhile, “counseling patients with MGUS on healthy lifestyle behaviors may be an important component of improving outcomes,” Dr. Lee said.

Limitations to the study were the low percentage of Black participants (6%) and its cross-sectional design. “We need more studies, including prospective and randomized controlled studies, to evaluate whether lifestyle interventions can impact myeloma-related outcomes,” Dr. Lee said. Researchers also recognize MS is not currently used as standard of care in routine medical practice, and therefore the impact of identified risk factors and MS-MGUS may be limited.

Any conflicts of interest declared by the authors can be found in the original article.


Lee DJ, El-Khoury H, Tramontano AC, et al. Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population. Blood Adv. 2024;8(7):1737-1746.


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