Paraprotein and MGUS Risk Interpreter — Mayo Risk, IMWG Limits
Paraprotein and MGUS Risk Interpreter — Mayo Risk, IMWG Limits
Enter the paraprotein (M-protein) band, its type and the free light chain ratio, with marrow, urine and end-organ findings if you have them. It gives the Mayo MGUS risk group with the published 20-year progression risks, and checks the result against the IMWG 2014 boundaries between MGUS, smouldering myeloma and myeloma — including the SLiM-CRAB myeloma-defining events, IgM paraproteins and light-chain MGUS, to which the Mayo model does not apply.
Paraprotein (MGUS) risk
M-protein + type + FLC → riskIgA paraprotein 18 g/L, normal FLC ratio, no marrow, no end-organ damage, no MRI, urine not measured
The Mayo MGUS risk model (Rajkumar 2005)
| Risk factors | Patients | 20-year progression | Allowing for competing death |
|---|---|---|---|
| 0 — low | 449 | 5% | 2% |
| 1 — low-intermediate | 420 | 21% | 10% |
| 2 — high-intermediate | 226 | 37% | 18% |
| 3 — high | 53 | 58% | 27% |
| Total | 1,148 |
IMWG 2014 boundaries
| MGUS (non-IgM) | Smouldering myeloma | Myeloma | |
|---|---|---|---|
| Serum M-protein | Below 30 g/L | IgG or IgA 30 g/L or more | Any |
| Urinary M-protein | — | 500 mg/24 h or more | Any |
| Clonal marrow plasma cells | Below 10% | 10% to 60% | 10% or more, or a plasmacytoma |
| Myeloma-defining event | None | None | At least one: CRAB, or plasma cells 60% or more, FLC ratio 100 or more, more than one MRI lesion |
Three questions in order: is it myeloma, is it smouldering, and how likely is MGUS to progress?
A paraprotein found on electrophoresis is usually monoclonal gammopathy of undetermined significance, and usually stays that way: the IMWG put the risk of progression at roughly 1% a year. The job is to make sure it is not something more, and then to decide how closely to watch it.
This page asks the questions in that order. First the myeloma-defining events of the 2014 IMWG criteria: the CRAB features (calcium, renal failure, anaemia, bone lesions) and the three SLiM biomarkers added in 2014 — 60% marrow plasma cells, an involved:uninvolved free light chain ratio of 100 or more, and more than one focal lesion on MRI. Then the smouldering myeloma limits: an IgG or IgA M-protein of 30 g/L or more, a urinary M-protein of 500 mg/24 h or more, or 10–60% marrow plasma cells. Only then the Mayo risk model, which counts three features — size, type and FLC ratio — and gives a 20-year risk.
Two figures are printed for each Mayo group, and the difference matters. The absolute risk assumes the patient lives 20 years; the competing-risk figure allows for death from other causes and is roughly half. For an 80-year-old with low-risk MGUS, the second is the honest number.
Two paraproteins fall outside the model. IgM progresses mainly to Waldenström macroglobulinaemia and lymphoma, and has its own limits. Light chain only is defined by the FLC ratio, progresses slowly, and is being redefined with age- and kidney-adjusted limits. For the ratio itself, including the renal range, use the serum free light chain ratio calculator; for staging established myeloma, the ISS myeloma staging calculator.
Frequently asked questions
What are the risk factors for MGUS progression?
The Mayo model uses three: an M-protein of 15 g/L (1.5 g/dL) or more, a non-IgG type (IgA, IgM or biclonal) and an abnormal serum free light chain ratio (below 0.26 or above 1.65). With 0, 1, 2 and 3 factors the 20-year risk of progression was 5%, 21%, 37% and 58%, or 2%, 10%, 18% and 27% allowing for death from other causes.
What is the difference between MGUS and smouldering myeloma?
Under the 2014 IMWG criteria, smouldering myeloma has an IgG or IgA M-protein of 30 g/L or more, a urinary M-protein of 500 mg/24 h or more, or 10–60% clonal plasma cells in the marrow, with no myeloma-defining event. MGUS has an M-protein below 30 g/L and fewer than 10% plasma cells.
What are the SLiM-CRAB criteria?
They are the myeloma-defining events. CRAB: raised calcium, renal insufficiency, anaemia and bone lesions attributable to the plasma cell disorder. SLiM, added in 2014: sixty per cent or more clonal plasma cells, a light chain ratio (involved:uninvolved) of 100 or more with the involved chain at least 100 mg/L, and more than one focal MRI lesion of 5 mm or more.
How often should MGUS be monitored?
The IMWG 2010 consensus suggests low-risk MGUS (IgG, below 15 g/L, normal FLC ratio) is rechecked at six months and then every 2–3 years, or sooner with symptoms; intermediate- and high-risk MGUS at six months and then yearly for life.
Does the Mayo model apply to light-chain MGUS?
No. It was built for MGUS with a heavy-chain M-protein. Light-chain MGUS is defined by an abnormal FLC ratio with no heavy chain on immunofixation, and progressed at about 0.3% a year in the Olmsted County cohort.
Related calculators
References
- Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106(3):812–817. — 1,148 patients with MGUS from south-eastern Minnesota; risk factors M-protein 15 g/L or more, non-IgG isotype (IgA, IgM, biclonal) and an abnormal FLC ratio (below 0.26 or above 1.65); 20-year progression 5%, 21%, 37% and 58% with 0, 1, 2 and 3 risk factors (449, 420, 226 and 53 patients), and 2%, 10%, 18% and 27% after accounting for death as a competing risk.
- Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–e548. — CRAB: calcium more than 0.25 mmol/L above the upper limit or above 2.75 mmol/L; creatinine clearance below 40 mL/min or creatinine above 177 µmol/L; haemoglobin more than 20 g/L below the lower limit or below 100 g/L; one or more osteolytic lesions. SLiM: clonal marrow plasma cells 60% or more; involved:uninvolved FLC ratio 100 or more with the involved chain at least 100 mg/L; more than one focal MRI lesion of 5 mm or more. Smouldering myeloma: serum M-protein (IgG or IgA) 30 g/L or more, or urinary M-protein 500 mg/24 h or more, and/or clonal marrow plasma cells 10–60%, without a myeloma-defining event. Non-IgM MGUS: M-protein below 30 g/L, marrow plasma cells below 10%, no end-organ damage. IgM MGUS: IgM M-protein below 30 g/L, lymphoplasmacytic infiltration below 10%. Light-chain MGUS: abnormal FLC ratio with an increased involved chain, no heavy chain on immunofixation, marrow plasma cells below 10%, urinary M-protein below 500 mg/24 h. (Criteria read from the International Myeloma Foundation’s reproduction of the paper.)
- Kyle RA, Durie BGM, Rajkumar SV, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24(6):1121–1127. — progression "approximately 1% per year"; low-risk MGUS ("M protein below 15 g/l, IgG type and a normal free light chain ratio") re-checked at six months and then every 2–3 years; intermediate and high risk at six months and then annually for life.
- Dispenzieri A, Katzmann JA, Kyle RA, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet. 2010;375(9727):1721–1728. — prevalence about 0.8% over 50, progression about 0.3% per year (figures as summarised by Long 2025; the Lancet abstract could not be retrieved).
- Einarsson Long T, et al. New definition of light chain monoclonal gammopathy of undetermined significance. JAMA Oncol. 2025;11:753–761. — the iStopMM group’s age- and kidney-function-adjusted FLC intervals for light-chain MGUS, from screening 75,422 people (read in a secondary source; not an IMWG criterion).
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.