The prognostic value of baseline sFLC measurements has been validated in a number of other studies . For example, in a retrospective study Turesson et al.  monitored 728 Swedish MGUS patients for up to 30 years (median 10 years). During which time, 84 patients developed a lymphoid disorder, with MM accounting for the majority (53/84) of cases. The κ/λ sFLC ratio was abnormal in 47% of the study population at baseline. Three risk factors were significantly associated with progression: an abnormal κ/λ sFLC ratio, monoclonal protein concentration (>15 g/L) and a reduction of one or two uninvolved immunoglobulin isotypes (immunoparesis). No association was found between the monoclonal protein isotype and risk of progression, which is in contrast to some previous reports , but in keeping with those of the Spanish PETHEMA group . This Spanish group also previously identified immunoparesis as a significant risk factor for MGUS progression in univariate but not multivariate analysis .
Rajkumar et al.  constructed an MGUS risk stratification model based on the size and type of monoclonal protein, and the presence of an abnormal κ/λ sFLC ratio at diagnosis (Table 13.2 and Figure 13.3. Using this model, low-risk patients were characterised as those with a small (<15 g/L) IgG monoclonal protein and a normal sFLC ratio. Such patients had a 2% absolute risk of disease progression at 20 years when competing causes of death were taken into account. Importantly, this low-risk group accounted for approximately 40% of the cohort. A smaller group of high-risk patients were identified as those with a large (>15 g/L) IgA or IgM monoclonal protein and an abnormal sFLC ratio. These patients had a 27% absolute risk of progression at 20 years.
|Risk of progression||No. of abnormal risk factors||No. of patients||Absolute risk of progression at 20 years*|
|* Accounting for death as a competing risk.
The three risk factors are defined as an abnormal κ/λ sFLC ratio (<0.26 or >1.65), a high serum monoclonal protein concentration (>15 g/L), and a non–IgG subtype (IgA or IgM).
Table 13.2. Risk stratification model to predict progression of MGUS .
International Myeloma Working Group (IMWG) guidelines  recommend that patients with MGUS should be risk stratified at diagnosis to optimise counselling and follow-up, using the risk-stratification model outlined in Table 13.2 (see Chapter 25, Table 25.3). For patients with low-risk MGUS, follow-up is recommended at 6 months initially and, if stable, every 2 - 3 years or when symptoms suggest evidence of a plasma cell malignancy. For these patients, a baseline bone marrow examination or skeletal radiography is not routinely indicated. For patients with intermediate- and high-risk MGUS, follow-up is recommended at 6 months initially, then annually and/or upon any change in the patient's clinical condition. A bone marrow aspirate and biopsy should also be carried out at baseline to rule out any underlying plasma cell malignancy .
In future, additional markers may be added to risk stratification models to better define high-risk patients. Rawstron et al.  have recently showed that plasma cell phenotype (CD138/38/45 expression) and sFLCs provide independent and complementary prognostic information on the risk of progression. The use of additional genetic risk factors (including light chain gene rearrangements  and gene expression profiles ) are currently being investigated.