MGUS is of clinical significance
Monoclonal Gammopathy of Undetermined Significance is more than just a precursor to Multiple Myeloma.
Patients diagnosed with MGUS have a significantly reduced life expectancy and a heightened mortality risk from lymphoproliferative disorders, most notably Multiple Myeloma. Furthermore, these patients face an elevated risk of mortality due to bacterial infections, as well as cardiovascular, renal, and hepatic diseases1.
Download this literature review to learn more about the clinical significance of MGUS
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What are monoclonal gammopathies such as MGUS?
Monoclonal gammopathies are a group of disorders characterized by the production of a monoclonal protein (M-protein) by clonal plasma cells. These M-proteins are fully formed antibodies and free light chains which form part of the antibody but are produced in excess. MGUS is a premalignant condition that can progress to Multiple Myeloma and is also associated with multiple comorbidities.
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Figure adapted from Kumar8 Nat Rev Dis Primers 2017
How is MGUS diagnosed?
Approximately 5% of the population over 50 years of age have MGUS9.
Typically, MGUS is asymptomatic and is most commonly discovered incidentally when blood tests are ordered to investigate other health conditions. Common ailments in the older population such as bone pain and mild anemia often result in blood tests being ordered. These tests may reveal the presence of an underlying monoclonal protein. Diagnostically, MGUS is defined as10:
What is the clinical significance?
Patients with MGUS have a 1% annual risk of progressing to Multiple Myeloma and this risk persists indefinitely1.
MGUS can also develop into monoclonal gammopathy of clinical significance (MGCS). This occurs when the M-proteins produced by the clonal plasma cells behind MGUS start to collect in organs. The deposition of M-proteins in organs can lead to organ dysfunction and damage. The most commonly affected organs include:
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The expansion of MGUS related plasma cells in the bone marrow can have negative effects on bone structural integrity and the bone marrow environment. This can lead to increased rates of:5-7
Bone disease6
MGUS may be associated with an increased risk of osteoporosis and fractures
Thrombosis7
MGUS patients are at increased risk of thrombosis, which may lead to conditions such as deep vein thrombosis or stroke
Infections5
MGUS patients have a higher risk of bacterial infections, likely due to immune dysfunction
MGUS patients should be monitored regularly
Patient evaluations should focus on early signs of progression and the development of MGCS and other comorbidities.
Prompt recognition of these symptoms allows for early intervention and improved patient outcomes.
"I think that a primary carer is ideally positioned to follow up patients with monoclonal gammopathy of undetermined significance (MGUS) and the frequency of evaluation would really be determined by the haematologist that's evaluated the patient. But in most cases, patients with MGUS, can be followed up every 6 to 12 months."
Professor Andrew Spencer
Head of Malignant Haematology, Stem Cell Transplantation and Head of Myeloma Research
The Alfred Hospital, Australia
Haematologists can provide specialist advice and support tools to primary care providers, who are ideally positioned to monitor patients with low-risk MGUS.
This animation is an example of some of the support tools we can provide.
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References
- Kristinsson SY, Bjorkholm M, Andersson TML, Eloranta S, Dickman PW, Goldin LR, Blimark C, et al. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study. Haematologica 2009 2009;94 12:1714-20 as doi: 10.3324/haematol.2009.010066.
- Leung N, Bridoux F, Hutchison CA, Nasr SH, Cockwell P, Fermand JP, Dispenzieri A, et al. Monoclonal gammopathy of renal significance (MGRS): when MGUS is no longer undetermined or insignificant. Blood 2012 10/9/2012;120 22:4292-5 as doi: blood-2012-07-445304 [pii];10.1182/blood-2012-07-445304 [doi].
- Nobile-Orazio E. Neuropathy and monoclonal gammopathy. In: Said G, Krarup C, editors. Handbook of Clinical Neurology. Elsevier; 2013. p. 443-59.
- Claveau J-S, Wetter DA, Kumar S. Cutaneous manifestations of monoclonal gammopathy. Blood Cancer Journal 2022 2022/04/11;12 4:58 as doi: 10.1038/s41408-022-00661-1.
- Kristinsson SY, Tang M, Pfeiffer RM, Bjorkholm M, Goldin LR, Blimark C, Mellqvist UH, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica 2012 6/2012;97 6:854-8 as doi: haematol.2011.054015 [pii];10.3324/haematol.2011.054015 [doi].
- Kristinsson SY, Tang M, Pfeiffer RM, Bjorkholm M, Blimark C, Mellqvist UH, Wahlin A, et al. Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood 2010 2010;116 15:2651-5 as doi: blood-2010-04-282848 [pii] 10.1182/blood-2010-04-282848.
- Kristinsson SY, Fears TR, Gridley G, Turesson I, Mellqvist UH, Bjorkholm M, Landgren O. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 2008 2008;112 9:3582-6 as doi: blood-2008-04-151076 [pii] 10.1182/blood-2008-04-151076.
- Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, et al. Multiple Myeloma. Nat Rev Dis Prim 2017;4 1-20.
- Love TJ, Rögnvaldsson S, Thorsteinsdottir S, Aspelund T, Reed ER, Vidarsson B, Onundarson PT, et al. Prevalence of MGUS Is High in the iStopMM Study but the Prevalence of IgA MGUS Does Not Increase with Age in the Way Other Immunoglobulin Subtypes Do. Blood / Presented at ASH 2022;140 Supplement 1:103a as doi: 10.1182/blood-2022-163169.
- Rajkumar SV, Dimopolous MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014 2014;15 12:e538-e48. Epub 20141026 as doi: 10.1016/S1470-2045(14)70442-5.