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An online educational resource with continuously updated information on serum free light chain and Hevylite® analysis.

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Home> Clinical> Haematology> Monoclonal Gammopathy of Undetermined Significance (MGUS)
Monoclonal Gammopathy of Undetermined Significance (MGUS)
   

Monoclonal gammopathy of undetermined significance is an asymptomatic condition that occurs in 1% of the population over 50 years of age, and >3% over 70 years of age. It is traditionally associated with the presence of a low level monoclonal band (<20g/L) in the serum, usually no light chains in the urine and <5% plasma cells in the bone marrow. Monitoring of MGUS patients is essential as a significant percentage (approximately 1% per annum) progress to develop Multiple Myeloma or related malignant condition.

An abnormal Freelite® serum free light chain ratio has been identified as an important, independent risk factor for progression of MGUS to myeloma or related malignancies.1

In a study of 1148 MGUS patients seen at the Mayo clinic between 1960 and 1994, an abnormal serum kappa/ lambda ratio was identified as a major independent risk factor for progression of MGUS to myeloma or a related malignancy.1

This risk stratification identified a low risk subset (40%) with a remarkable small life-time risk of progression, only 2% over 20 years.

   

Risk of progression of MGUS to myeloma

Risk of progression of MGUS to myeloma or related disorder using a risk-stratification model that incorporates the Freelite® FLC ratio and the size and type of the serum monoclonal protein. The top curve illustrates risk of progression with time in patients with all 3 risk factors, namely an abnormal serum kappa-lambda FLC ratio (< 0.26 or >1.65), a high serum monoclonal protein level (> 15 g/L), and non-IgG MGUS; the second gives the risk of progression in patients with any 2 of these risk factors; the third curve illustrates the risk of progression with one of these risk factors; the bottom curve is the risk of progression for patients with none of the risk factors.

Blood:journal of the American Society of Hematology Copyright 2005 by AMERCIAN SOCIETY OF HEMATOLOGY (ASH) in the format Internet posting via Copyright clearance Center.

 

progression of monoclonal gammopathy of undetermined significance to multiple myeloma Effect of increasingly abnormal Freelite® FLC ratio on the relative risk of progression of monoclonal gammopathy of undetermined significance to multiple myeloma or related disorder. This figure illustrates that as the serum kappa-lambda FLC ratio becomes increasingly abnormal, the risk of progression increases.

Blood:journal of the American Society of Hematology Copyright 2005 by AMERCIAN SOCIETY OF HEMATOLOGY (ASH) in the format Internet posting via Copyright clearance Center.

 

Among newly diagnosed multiple myeloma, some 16% are reported to produce monoclonal light chains only.2 Freelite® has led to the improved detection of monoclonal gammopathies due to the increased sensitivity of serum free light chain assays. With the availability of Freelite the premalignant category: Light Chain Monoclonal Gammopathy of Undetermined Significance (LC MGUS), can now be characterised.

Light Chain MGUS is where there is an abnormal serum free light chain ratio and increased concentration of the involved light chain without detectable immunoglobulin heavy chain. This premalignant entity can evolve to light chain multiple myeloma, nonsecretory multiple myeloma and also intact immunoglobulin multiple myeloma and other related b cell malignancies.3,4,5

A recent retrospective study at Mayo Clinic reported that 19% of cases of MGUS are light chain MGUS. This study also described the prevalence of LC MGUS in the general population over 50 (population based cohort of 21,463) as 0.8%, contributing to an overall MGUS prevalence of 4.2%. The risk of progression to multiple myeloma was reported as 0.3% per 100 person years.6 It is also of note that renal disorders were identified in 23% of LC MGUS patients at diagnosis or follow up.6 This suggests that patients with Light Chain MGUS may need closer monitoring to detect development of renal disease.7

Now for the first time you can simply and easily identify and monitor this group of patients with Freelite®.

The International Myeloma Working Group has recently published guidelines for monitoring and management of MGUS and smoldering multiple myeloma. Freelite® is included in the guidelines as a predictor of risk of progression for MGUS patients.

 

Risk Group Numbers of patients Absolute risk of progression at 20 years*
LOW
(serum M protein <1.5 gm/dL, IgG subtype, Normal Freelite® FLC ratio)
 		  449  2%
LOW INTERMEDIATE RISK
(Any 1 factor abnormal)		  420  10%
HIGH INTERMEDIATE RISK
(Any 2 factors abnormal)
 		  226  18%
HIGH RISK
(All 3 factors abnormal)		  53 27% 

Blood:journal of the American Society of Hematology Copyright 2005 by AMERCIAN SOCIETY OF HEMATOLOGY (ASH) in the format Internet posting via Copyright clearance Center.

Freelite® can contribute to the management of your MGUS patients.

  • Low risk patients may account for 40% of all MGUS patients1  
     
  • Freelite® enables you to provide reassurance to low risk MGUS patients 
     
  • High risk patients may account for 5% of all MGUS patients1 
     
  • Freelite® enables you to identify high risk patients and monitor more closely8 
     
  • Risk stratification of MGUS patients with Freelite® will enable you to allocate resources appropriately8 
     
  • Freelite® enables identification of Light Chain MGUS 4,5,7
     
  • Freelite® enables monitoring of Light Chain MGUS for progression to Multiple Myeloma 3,8

Request a copy of this useful review - Weiss, B.M., Abadie, J., Verma, P. et al. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood, 2009. 113(22): p. 5418-22

Click here for ordering information

 

  1. S.Vincent Rajkumar, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance (MGUS). Blood 2005;106;3: 812-817 Request you copy - code MKG563
  2. Katzman J.A, et al. Elimination of the Need for Urine Studies in the Screening Algorithm for Monoclonal Gammopathies by Using Serum Immunofixation and Free Light Chain Assays. Mayo Clin Proc 2006; 81:1575-1578 Request your copy - code MKG343
  3. Weiss and Kuehl. Advances in understanding monoclonal gammopathy of undetermined significance as a precursor of multiple myeloma. Expert Rev. Hematol 2010; 3(2), 165-174 Request you copy - code MKG569
  4. Weiss, et al. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009; 113: 5418-5422
  5. Tsai, et al. Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study. Blood 2009; 114: 4928-4932
  6. Dispenzieri. et al, Prevalance and risk of progression of light chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet vol 375 may 15 1721-1728  Request your copy - code MKG608
  7. Frits van Rhee. Light-chain MGUS: implications for clinical practice. Lancet 2010; 375:1670-1671
  8. Kyle, R.A, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asympomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia, 2010; 24: 1121 - 1127 Request your copy - code MKG563