From the Guidelines
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by the presence of an abnormal protein (M protein) produced by plasma cells in the bone marrow, with a risk of progression to multiple myeloma or related disorders. The pathology of MGUS involves the clonal proliferation of plasma cells that produce a monoclonal immunoglobulin, but these cells comprise less than 10% of the bone marrow. Diagnosis requires three criteria: serum M protein less than 30 g/L, bone marrow plasma cells less than 10%, and absence of end-organ damage (no hypercalcemia, renal insufficiency, anemia, or bone lesions) 1.
Key Diagnostic Criteria
- Serum M protein less than 30 g/L
- Bone marrow plasma cells less than 10%
- Absence of end-organ damage (no hypercalcemia, renal insufficiency, anemia, or bone lesions) The prognosis is generally favorable, with most patients never developing a malignancy. However, MGUS carries a risk of progression to multiple myeloma, Waldenström macroglobulinemia, or related disorders at a rate of approximately 1% per year 1.
Risk Factors for Progression
- Higher M protein concentration
- Non-IgG isotype
- Abnormal free light chain ratio
- Higher percentage of bone marrow plasma cells Management involves regular monitoring with serum protein electrophoresis, complete blood count, and calcium and creatinine measurements every 6-12 months, with frequency adjusted based on risk stratification 1.
Management
- Regular monitoring with serum protein electrophoresis
- Complete blood count
- Calcium and creatinine measurements every 6-12 months No specific treatment is required for MGUS itself, but patients should be educated about symptoms that might indicate progression to malignancy. The most recent and highest quality study recommends risk-stratification at diagnosis to optimize counseling and follow-up, with low-risk MGUS patients being followed less frequently, either every 2–3 years or at time of progression 1.
From the Research
Pathology of Monoclonal Gammopathy of Undetermined Significance (MGUS)
- MGUS is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year 2
- It is caused by a proliferation of monoclonal plasma cells leading to a detectable serum monoclonal protein and/or excess of plasma cells in the bone marrow 3
- Cytogenetic aberrations are detectable in the majority of patients in the clonally expanded plasma cells 3
Diagnosis of MGUS
- Prerequisite for the diagnosis is that plasma cell disease does not cause clinical symptoms 3
- Assessment of the risk of progression of patients with asymptomatic monoclonal gammopathies (MG) is based on various factors, including:
- Serum paraprotein (M protein) concentration
- Isotype of M protein
- Serum free light chain ratio
- Infiltration of bone marrow plasmocytes
- Reduction of one or two noninvolved immunoglobulin subtype levels (immunoparesis)
- Evolving and non-evolving subtype of MGUS
- Ratio of normal/abnormal plasma cells in bone marrow identified by multiparametric flow cytometry techniques
- Number of circulating plasma cells in peripheral blood 4
Prognosis of MGUS
- The lifetime risk of progression into symptomatic multiple myeloma lies between 15% and 59% for patients with MGUS or smoldering multiple myeloma (sMM) 3
- Prognostic parameters for development of symptomatic multiple myeloma from MGUS or sMM are:
- Concentration of monoclonal protein
- Bone marrow plasmocytosis
- A non-IgG subtype
- An abnormal free-light chain ratio
- Detection of more than 1 focal lesion in whole body MRI
- 95% or more of bone marrow plasma cells displaying an aberrant phenotype in flow cytometry
- An evolving clinical course in two consecutive follow-up visits 3, 4
- Three risk stratification models have been constructed that are useful in daily practice for predicting risk of progression of MGUS into malignant forms of monoclonal gammopathy: MAYO, PETHEMA, and CMG model 4