Monoclonal Gammopathy of Undetermined Significance (MGUS) - Summary Framework



Hematologic disorder characterized by the presence of either abnormal intact monoclonal immunoglobulins or their corresponding light-chain fragments.



Epidemiology:

• It is present in more than 3% of patients 50 years or older

• Prevalence M > F



MGUS can be categorized into 3 sub-types based on the hematologic cancer for which they carry the greatest future risk.



IgM MGUS:

• Serum IgM monoclonal protein level <3 g/dL

• Bone marrow lymphoplasmacytic infiltration <10%

• No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly

• 1.5% risk per year for progression to Waldenström macroglobulinemia

• Rarely, patients can progress to IgM multiple myeloma



Non-IgM MGUS:

• Serum monoclonal protein level (non-IgM type) < 3 g/dL

• Clonal bone marrow plasma cells < 10%

• Monoclonal immunoglobulin is an IgA or IgG isotype (rarely IgD or IgE)

• Absence of end-organ damage, such as hyperCalcemia, Renal insufficiency, Anemia, and Bone lesions (CRAB)

• 1% risk per year for progression to multiple myeloma, AL amyloidosis, or a related disorder



Light-Chain MGUS:

• Abnormal FLC ratio (<0.26 or >1.65)

• Increased level of the appropriate involved light chain (increased kappa FLC in patients with ratio >1.65 and increased lambda FLC in patients with ratio <0.26)

• No immunoglobulin heavy-chain expression on immunofixation

• Absence of end-organ damage that can be attributed to the plasma cell proliferative disorder

• Clonal bone marrow plasma cells < 10%

• Urinary monoclonal protein level < 500 mg/24 h

• Risk for progression to light-chain myeloma and AL amyloidosis

• Rate of progression not defined



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