Patients must be appropriately counselled that MGUS is a pre-malignant entity with a relatively low risk of progression to multiple myeloma or related malignancies.
Because patient risk stratification can be difficult and there are no markers or clinical findings at diagnosis to determine whether a specific patient is at risk of progression (to multiple myeloma or related plasma cell proliferative malignancy), many experts recommend that all MGUS patients should be followed up annually (for life) to detect serious disease before complications such as renal failure or pathologic fractures occur. Clinicians must use clinical measures in combination with routine blood tests (including renal function, hemoglobin, and serum calcium) and serum and urine monoclonal protein markers to monitor MGUS patients.[31]van de Donk NW, Palumbo A, Johnsen HE, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica. 2014 Jun;99(6):984-96.
https://www.doi.org/10.3324/haematol.2013.100552
http://www.ncbi.nlm.nih.gov/pubmed/24658815?tool=bestpractice.com
International Myeloma Working Group (IMWG) guidelines recommend that patients diagnosed with intermediate-risk or high-risk MGUS should be followed up 6 months after initial detection, and then annually for life.[32]Kyle RA, Durie BG, Rajkumar SV, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun;24(6):1121-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020664
http://www.ncbi.nlm.nih.gov/pubmed/20410922?tool=bestpractice.com
One study suggested that low-risk MGUS patients may not need to be followed up annually but rather can be followed up if they have new symptoms or signs such as bone pain, weight loss, fatigue, bleeding, disrupted urinary function, repeated infections, or other symptoms suggesting progression.[29]Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005 Apr 26;106(3):812-7.
https://www.doi.org/10.1182/blood-2005-03-1038
http://www.ncbi.nlm.nih.gov/pubmed/15855274?tool=bestpractice.com
[33]Bird J, Behrens J, Westin J, et al. UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol. 2009 Oct;147(1):22-42.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2141.2009.07807.x
http://www.ncbi.nlm.nih.gov/pubmed/19673884?tool=bestpractice.com
For patients with a low-risk stratification at diagnosis, IMWG guidelines recommend serum protein electrophoresis in 6 months and, if stable, follow-up every 2 to 3 years.[32]Kyle RA, Durie BG, Rajkumar SV, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010 Jun;24(6):1121-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020664
http://www.ncbi.nlm.nih.gov/pubmed/20410922?tool=bestpractice.com