25.5. UK Myeloma Forum and Nordic Myeloma Study Group: guidelines for the investigation of newly detected monoclonal proteins and management of monoclonal gammopathy of undetermined significance (2009)

Chapter 25
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These 2009 guidelines [28] recommend screening for monoclonal proteins in patients where there is clinical suspicion of plasma cell dyscrasia or B-cell malignancy. Screening should also be performed when the results of other laboratory tests raise the possibility of the presence of a monoclonal protein (such as raised erythrocyte sedimentation rate [ESR >30 mm/h], anaemia, renal failure, hypercalcaemia). SPE and UPE should be performed initially, and if the clinical suspicion of an underlying plasma cell dyscrasia is strong despite the absence of a detectable monoclonal protein, then IFE should be requested. sFLC analysis is required to detect NSMM and some cases of AL amyloidosis, and LCMM when urine is not available. sFLC analysis is also advised where serum immunoglobulin levels are low and no serum monoclonal protein is identified. Alternatively, a urine sample may be requested for IFE.

The guidelines also discuss the MGUS risk-stratification model published by Rajkumar et al. [257] and the value of the κ/λ sFLC ratio, along with monoclonal protein level and immunoglobulin type, in differentiating patients at low to high risk of malignant transformation. According to these guidelines [28], the frequency of monitoring MGUS patients considered to be at low-risk, particularly those with low paraprotein concentrations, could be reduced if actual life expectancy is low and all lymphoproliferative diseases other than MGUS have been excluded. This is in agreement with the IMWG guidelines (Section 25.3.2) [27]. For those patients with longer life expectancies, higher monoclonal protein levels, and non-IgG subtypes, monitoring every 3 - 4 months within the first year was advised and thereafter once or twice yearly in the absence of symptoms of progression. It is additionally noted that for MGUS patients with an abnormal baseline κ/λ sFLC ratio or significant Bence Jones proteinuria, the risk of renal failure and disease progression is increased. These patients should be considered for more frequent monitoring and be advised to maintain high fluid intake.