It is not yet clear, furthermore, why only some patients progress from MGUS to myeloma.

With colleagues, Dr Landgren has reported that high body mass index (BMI) at midlife appears to be associated with a greater risk of progressing from MGUS to myeloma or other lymphoproliferative diseases. This association might involve circulating levels of the metabolic hormone adiponectin, which is underexpressed in overweight people and was lower among patients who progressed from MGUS to multiple myeloma.7,8

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“Overall, the absolute risk of progression from monoclonal gammopathy to myeloma is low,” Dr Landgren told Cancer Therapy Advisor — less than 1% a year overall, complicating prospective research efforts.

Researchers are working to develop predictive molecular markers.

“Currently, there are no established genetic markers or more sophisticated biomarkers,” Dr Landgren said. “Ongoing studies are investigating the role of genetic signatures in the abnormal plasma cells, patterns of host-immune cells, and other markers.”

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It is also too soon to say if treating MGUS might prevent progression to myeloma.

“Given the low absolute risk of progression overall, any such drug has to be non-toxic and with a high rate of successful cure,” Dr Landgren said. “If better biomarkers were developed to identify individuals at high risk of progression, and better drugs that are non-toxic were available, the field would drastically change.”


  1. Kyle RA, Larson DR, Therneau TM, et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med. 2018;378:241-9. doi: 10.1056/NEJMoa1709974
  2. Panopoulou A, Streetly MJ. Myeloma and MGUS. Medicine. 2017;45:5.
  3. Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a progressive study. Blood. 2009;113:5412-7. doi: 10.1182/blood-2008-12-194241
  4. Landgren O, Graubard BI, Kumar S, et al. Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12 372 individuals 10-49 years old: a population-based study from the National Health and Nutrition Examination Survey. Blood Cancer J. 2017;7:e618. doi: 10.1038/bcj.2017.97
  5. Campbell JP, Heaney JL, Pandya S, et al. Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study. Lancet Haematol. 2017;4(12):e585-94.
  6. Landgren O. Serum protein markers of clonal heterogeneity in myeloma. Lancet Haematol. 2017;4(12):e565-6.
  7. Hofmann JN, Mailankody S, Korde N, et al. Circulating adiponectin levels differ between patients with multiple myeloma and its precursor disease. Obesity. 2017;25:1317-20. doi: 10.1002/oby.21894
  8. Thordardottir M, Lindqvist EK, Lund SH, et al. Obesity and risk of monoclonal gammopathy of undetermined significance and progression to multiple myeloma: a population-based study. Blood Adv. 2017;1:2186-92. doi: 10.1182/bloodadvances.2017007609