From the Guidelines
Patients with MGUS who experience a 25% increase in their M-protein level and have an M-protein concentration greater than 5 g/dL are at high risk for progression to multiple myeloma and should be urgently evaluated by a hematologist-oncologist. This recommendation is based on the study by 1, which found that the size of the M protein at the time of recognition of MGUS was the most important predictor of progression, with a 20-year risk of progression of 49% for those with an M-protein value of 25 g/l, compared to 14% for patients with an initial M-protein value of 5 g/l or less. Key points to consider in the evaluation of these patients include:
- The risk of progression with an M-protein value of 15 g/l was almost twice that of a patient with an M-protein value of 5 g/l, highlighting the importance of monitoring M-protein levels closely 1
- A progressive increase in size of the M protein during the first year of follow-up was the single most important risk factor for progression, as emphasized by Rosinol 1
- The recommended approach includes immediate referral to a hematologist-oncologist for comprehensive assessment, including:
- Bone marrow biopsy
- Complete skeletal survey or low-dose whole-body CT scan
- Serum free light chain assay
- Assessment for end-organ damage (CRAB features: hypercalcemia, renal insufficiency, anemia, and bone lesions)
- Laboratory tests should include complete blood count, comprehensive metabolic panel, serum and urine protein electrophoresis with immunofixation, and beta-2 microglobulin levels, as these can help identify signs of disease progression and guide treatment decisions. While awaiting specialist evaluation, patients should be monitored for symptoms such as bone pain, fatigue, recurrent infections, and signs of hyperviscosity syndrome, which may require immediate intervention.
From the Research
MGUS Increase by 25% and M-Protein >5 g/dL
- An increase in MGUS by 25% and an M-protein level greater than 5 g/dL may indicate a higher risk of progression to multiple myeloma or other malignant conditions 2.
- According to a study published in 1997, patients with MGUS have a 16% risk of developing multiple myeloma or other serious diseases within 10 years, 33% within 20 years, and 40% within 25 years 2.
- The size of the M-protein is an important factor in differentiating MGUS from multiple myeloma, with higher levels indicating a greater risk of progression 2, 3.
- A study published in 2020 found that bone marrow biopsy is not necessary for all patients with a monoclonal protein, but it is critical for diagnosis in some cases, particularly those with high-risk MGUS or smoldering multiple myeloma 4.
- The role of serum protein electrophoresis in detecting multiple myeloma was highlighted in a 2012 study, which found that it is an easy-to-perform laboratory test that can be used for detection and quantification of monoclonal gammopathy 3.
- Recent advances in MGUS diagnosis, risk stratification, and management have introduced the concept of myeloma-defining genomic events, which may help identify patients at higher risk of progression to multiple myeloma 5.
- A 2025 review of MGUS diagnosis and management emphasized the importance of differentiating MGUS from more serious conditions and using risk stratification to determine additional diagnostic testing, monitoring, and potential therapy 6.