What are the clinical signs of Immunoglobulin M (IgM) Monoclonal Gammopathy of Undetermined Significance (MGUS)?

From the Guidelines

IgM monoclonal gammopathy of undetermined significance (MGUS) is typically asymptomatic, with patients showing no clinical signs at diagnosis, and is often discovered incidentally during blood tests performed for other reasons. The defining laboratory finding is a serum IgM monoclonal protein concentration less than 3 g/dL, with no evidence of lymphoma, lymphoplasmacytic lymphoma (Waldenström macroglobulinemia), or other B-cell proliferative disorders 1. Bone marrow examination shows less than 10% lymphoplasmacytic cells, and there is no evidence of end-organ damage attributable to the monoclonal protein, such as hyperviscosity, symptomatic neuropathy, amyloidosis, or cryoglobulinemia. Some patients may develop mild peripheral neuropathy, particularly with prolonged disease duration. Regular monitoring is essential as IgM MGUS carries a risk of progression to malignant conditions at a rate of approximately 1-2% per year, as reported in a study by the European Myeloma Network 1. Monitoring typically includes serum protein electrophoresis, complete blood count, and clinical evaluation every 6-12 months to detect early signs of progression. The absence of symptoms distinguishes MGUS from more advanced plasma cell disorders, making it important to rule out other conditions when IgM monoclonal proteins are detected.

Key characteristics of IgM MGUS include:

• Serum IgM monoclonal protein concentration less than 3 g/dL
• Less than 10% lymphoplasmacytic cells in bone marrow examination
• No evidence of end-organ damage
• No symptoms or clinical signs at diagnosis
• Risk of progression to malignant conditions, such as Waldenström macroglobulinemia, at a rate of approximately 1-2% per year, as supported by a study published in Haematologica 1.

It is essential to note that the management of IgM MGUS involves regular monitoring, rather than immediate treatment, as most patients remain asymptomatic and do not require therapy, as recommended by the European Myeloma Network 1.

From the Research

Clinical Signs of IgM Monoclonal Gammopathy of Undetermined Significance (MGUS)

• The clinical signs of IgM MGUS are not explicitly stated in the provided studies, but the indications for prediagnostic testing include:
  • Neuropathy 2
  • Renal disease 2
  • Anemia 2
  • Bone disorder or connective tissue pain 2
  • Cutaneous disease 2
• These indications are not specific to IgM MGUS, but rather to MGUS in general
• The studies suggest that MGUS is often diagnosed incidentally, and the clinical signs may not be directly related to the condition 3, 4, 5
• The diagnosis of MGUS is based on the presence of a monoclonal protein (M protein) in the blood or urine, and the absence of end-organ damage or symptoms 4
• The subtype of immunoglobulin, M protein concentration, and free light chain ratio are used to risk-stratify patients with MGUS 4

Risk Stratification and Management

• Patients with low-risk MGUS can safely defer bone marrow biopsy and advanced imaging, and should undergo periodic laboratory monitoring 4
• Intermediate- and high-risk MGUS should trigger bone marrow biopsy and bone imaging to detect overt MM and shorter monitoring intervals 4
• Advanced molecular testing may improve on current risk stratification to target monitoring and treatment to those with highest risk of malignant progression and avoid overtreatment of those with low-risk disease 4