What is MGUS?
MGUS is of clinical significance
Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal protein in the serum of asymptomatic individuals who do not meet the diagnostic criteria for Multiple Myeloma, AL amyloidosis, Waldenström's macroglobulinaemia (WM), lymphoproliferative disorders, plasmacytoma or related conditions.
It was first described in 1978 ¹. The name was chosen as some patients with MGUS would go on to develop Multiple Myeloma but not all. Since then, many publications have demonstrated that MGUS is of clinical significance, even in patients who do not go on to develop Multiple Myeloma ².
Why is MGUS important?
MGUS can progress to Myeloma and can also cause organ damage
As well as progression to Multiple Myeloma or another lymphoproliferative disorder, patients with MGUS may develop monoclonal protein-related disorders, these may include autoantibody activity by the monoclonal protein or deposition of the monoclonal protein in tissues and the associated organ dysfunction, or conditions associated with changes in the bone marrow microenvironment caused by the underlying tumour.
These changes can lead to increased infection, osteoporosis, fractures and thrombosis ³. Patients with MGUS have an increased risk of death, not just through progression to Multiple Myeloma and other lymphoproliferative diseases but also bacterial infections, heart disease, liver diseases and kidney diseases 2. This is why it is important to evaluate patients with MGUS to detect these comorbidities and manage them.
What is Multiple Myeloma?
Serial evaluation of MGUS patients is important
Evaluation of patients with MGUS enables supportive care to be given if they develop any symptoms related to their monoclonal protein production, and also means that progression to Multiple Myeloma is detected earlier.
If progression to Multiple Myeloma is detected earlier, treatment can be given earlier, reducing the end organ damage the disease can cause, and improving patient outcome.
Patients with MGUS who are followed up and progress have fewer comorbidities at progression than patients first identified once they already have Multiple Myeloma 3,4 They also have a longer median overall survival ⁵.
Why is serum free light chain measurement useful in patients with MGUS?
"A rise in serum free light chain concentration may precede an increase in intact immunoglobulin concentrations and may be the first sign that a patient is progressing from MGUS to Multiple Myeloma6."
- MGUS can evolve to Multiple Myeloma
- The monoclonal protein can also cause organ damage without progression
- Evaluation of MGUS during follow up enables better care for MGUS patients
- Evaluation of previous diagnosed MGUS should including measurement of the monoclonal protein. Adding sFLC to SPE measurement allows evaluation of free light chains as well as intact immunoglobulins.
"An increasingly abnormal sFLC ratio may be a harbinger of symptomatic myeloma"
Weiss, B.M., et al., A monoclonal gammopathy precedes multiple myeloma in most patients. Blood, 2009. 113(22): p. 5418-5422.
3rd Party Websites
- https://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/common-cancers-compared#heading-Zero
- https://www.nhs.uk/conditions/multiple-myeloma/
- https://themmrf.org/multiple-myeloma/
- https://www.amyloidosis.org.uk/about-amyloidosis/al-amyloidosis/symptoms-and-signs-of-al-amyloidosis/
References
- Kyle, R.A., Monoclonal gammopathy of undetermined significance. Natural history in 241 cases. Am J Med, 1978. 64(5): p. 814-826.
- Kristinsson, S.Y., et al., Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study. Haematologica, 2009. 94(12): p. 1714-1720.
- van de Donk, N.W., et al., The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica, 2014. 99(6): p. 984-996.
- Go, R.S., J.D. Gundrum, and J.M. Neuner, Determining the clinical significance of monoclonal gammopathy of undetermined significance: a SEER-medicare population analysis. Clin Lymphoma Myeloma Leuk, 2015. 15(3): p. 177-186.
- Sigurdardottir, E., et al., The role of diagnosis and clinical follow-up of monoclonal gammopathy of undetermined significance on survival in multiple myeloma. JAMA Oncology, 2015. 1(2): p. 168-174.
- Weiss, B.M., et al., A monoclonal gammopathy precedes multiple myeloma in most patients. Blood, 2009. 113(22): p. 5418-5422.