From the Guidelines
Patients with MGUS should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2–3 years or when symptoms suggestive of a plasma cell malignancy arise. MGUS, or Monoclonal Gammopathy of Undetermined Significance, is a precancerous condition characterized by the presence of an abnormal protein (M protein) in the blood produced by plasma cells. This condition requires regular monitoring but typically doesn't need immediate treatment.
Key Considerations
- The risk of progression to multiple myeloma or related blood cancers is approximately 1% per year, as noted in studies such as 1.
- Risk factors for progression include higher M protein levels (>1.5 g/dL), non-IgG type M protein, abnormal free light chain ratio, and abnormal bone marrow plasma cell percentage.
- While no specific medications are needed for MGUS itself, maintaining bone health with adequate calcium and vitamin D is recommended.
- MGUS is relatively common, affecting about 3% of people over age 50, and results from genetic mutations in plasma cells that cause them to produce identical abnormal proteins, as discussed in 1 and 1.
Monitoring and Management
- Patients with low-risk MGUS, characterized by an M protein <15 g/l, IgG type, and a normal free light chain (FLC) ratio, can be followed less frequently, either every 2–3 years or at the time of progression, as suggested by 1.
- Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life.
- Testing should be done 2–3 months after the initial recognition of smoldering (asymptomatic) multiple myeloma (SMM), and if the results are stable, the patient should be followed every 4–6 months for 1 year and, if stable, every 6–12 months, as recommended by 1.
From the Research
Definition and Epidemiology of MGUS
- Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of myeloma-defining event 2.
- Nearly 5% of adults have MGUS, a precursor malignant condition 3.
- The risk of progression to multiple myeloma (MM) varies greatly for individual patients, but it is uniform and 1% per year for MGUS 2.
Diagnosis and Management of MGUS
- Management of MGUS centers on differentiating it from more serious conditions to determine additional diagnostic testing, monitoring, and potential therapy 3.
- Guideline-concordant management of MGUS is determined by predicted risk of progression to malignant disease, which depends on subtype of immunoglobulin, M protein concentration, and free light chain ratio 3.
- Patients with low-risk MGUS can safely defer bone marrow biopsy and advanced imaging, and should undergo periodic laboratory monitoring 3.
- Intermediate- and high-risk MGUS should trigger bone marrow biopsy and bone imaging to detect overt MM and shorter monitoring intervals 3.
Relationship between MGUS and Smoldering Multiple Myeloma (SMM)
- SMM is an asymptomatic disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10-60% bone marrow plasma cell infiltration with no myeloma-defining event 2.
- SMM is a heterogeneous clinically defined condition in which some patients have MGUS (pre-malignancy), and some have MM (biologic malignancy) 4.
- The risk of progression to MM is higher for SMM patients, with approximately 10% per year, and is not uniform 2.
Treatment and Prevention of MGUS and SMM
- The standard of care is observation for MGUS patients, although early intervention may be beneficial for high-risk SMM patients 2, 4.
- Patients with newly diagnosed high-risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials 4.
- Research using novel detection methods, incorporating molecular testing into risk stratification, and evaluating screening, monitoring, and therapeutic or lifestyle interventions has the potential to improve outcomes 3, 5, 6.