MGUS patients have M proteins (IgG kappa or lambda; or IgA kappa or lambda) in the serum but without features of multiple myeloma, macroglobulinaemia, amyloidosis, or lymphoma (1).
- they have fewer than 10% of plasma cells in the bone marrow
- patients are asymptomatic and should avoid treating them (1)
In smouldering myeloma, patients have similar characteristics but may have more than 10% of marrow plasma cells (1)
MGUS can be seen in 2% of people older than 50 years (2) and around 1% of MGUS patients per year will progress to myeloma (most commonly), amyloidosis, lymphoma, or chronic lymphocytic leukaemia.
- they must be followed carefully because patients who develop these diseases require treatment
- almost all patients with multiple myeloma are preceded by a gradually rising level of MGUS
- the following risk factors suggest disease progression
- an abnormal serum-free light chain ratio
- non-IgG class MGUS.
- a high serum M protein level (≥15 g/L) (1)
Note that although the risk of malignant progression among patients with MGUS is considered to be 1% per year, the actual lifetime probability of progression is lower when adjusted for competing causes of death and is approximately 11% at 25 years (3):
- MGUS is asymptomatic but can progress to cancer — specifically, multiple myeloma, Waldenström’s macroglobulinemia, or solitary plasmacytoma - at a rate of 1% per year
- risk is persistent and does not diminish over time, even after 25 years of follow-up
- risk increases proportionally with the serum M protein concentration and the degree of skewing in the serum free light-chain (FLC) ratio
- risk is higher with the IgM or IgA subtype of MGUS
- for persons with all three risk factors (a serum M protein level of ≥1.5 g per deciliter, IgA or IgM MGUS, and an abnormal serum FLC ratio), the risk of progression at 20 years is 58%, as compared with 5% for persons who have none of these risk factors
The following criteria are used for the diagnosis of MGUS (all three are required):
- serum monoclonal protein low *
- monoclonal bone marrow plasma cells of 10%
- no evidence of end-organ damage attributable to the clonal plasma cell disorder:
- normal serum calcium, haemoglobin level and serum creatinine
- no bone lesions on full skeletal X-ray survey and/or other imaging if performed
- no clinical or laboratory features of amyloidosis or light chain deposition disease (1)
* low is defined as serum M protein of 3.0 g per 100 ml (4).
Reference:
- National Cancer Institute 2011. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment
- Nau KC, Lewis WD. Multiple myeloma: diagnosis and treatment. Am Fam Physician. 2008;78(7):853-9.
- Rajkuma SV et al. Monoclonal Gammopathy of Undetermined Significance. NEJM 2025;393:1315-1326
- Palumbo A et al. International Myeloma Working Group guidelines for the management of multiple myeloma patients ineligible for standard high-dose chemotherapy with autologous stem cell transplantation. Leukemia. 2009;23(10):1716-30.