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

8, 9, 10, 15
Home> Clinical> Haematology> Patient Management Stage> Monitoring
Monitoring
   

Freelite® – Recommended for Monitoring Treatment & Disease

The International Myeloma Working Group guidelines recommend the serial assessment of free light chain levels in all patients with AL amyloidosis and in Multiple Myeloma patients with oligosecretory disease. Additionally they recommend monitoring Intact Immunoglobulin Multiple Myeloma patients periodically to identify light chain escape. They also recommend use of Freelite® in all patients who achieve a complete response to determine if there is a stringent complete response.
The advice was based upon results obtained in extensive clinical trials using the polyclonal Freelite® assays.1

Monitor more patients accurately and easily

Freelite® offers a sensitive indicator of patient status in treatment and remission of Multiple Myeloma and AL amyloidosis. Freelite provides a rapid, quantifiable measure of serum free light chains to aid laboratory diagnosis and monitoring of monoclonal disease states.

  • Free light chains have a half-life of just 2-6 hours in serum and can be used confidently as a rapid indicator of response to treatment1
     
  • Freelite® is highly specific and sensitive for serum kappa and lambda free light chains1
     
  • Freelite® has a sensitivity much greater than currently available urine assays2
     
  • Freelite® enables you to identify the status of patients even if a different monoclonal protein is produced in relapse3
     
  • Freelite® can be used to monitor the majority of Multiple Myeloma patients offering improved patient management4
     
  • Freelite® may be useful when there are low concentrations of intact immunoglobulin which makes measurement unreliable4
     
  • Freelite® allows prompt identification and treatment of relapsing IIMM patients with light chain escape5,6,3
     
  • Freelite® is a sensitive marker of residual disease7
     
  • Freelite® reflects tumour killing more rapidly than quantification of Intact Immunoglobulin8
     
  • Freelite® provides early indication of resistance to treatment9
     
  • Freelite® assay time is less than 20 minutes, facilitating rapid clinical decisions.

Freelite® can be used to monitor all types of Multiple Myeloma. See disease types below for more information.
 

  • Most “Nonsecretory Multiple Myeloma” patients can now be monitored more easily, using a serum sample.
     
  • Freelite® improves the precision of monitoring NSMM patients compared to traditional methods
     
  • Monitor the majority of Nonsecretory Multiple Myeloma patients without compromise
     
  • The number of bone marrow biopsies for this group of patients can be reduced
     
  • Reduce patient anxiety with fewer bone marrow biopsies
 
Freelite® detected abnormal serum free light chains in 82% of patients previously classified as non secretors by conventional methods. The sensitivity of Freelite® can help to detect and monitor these patients effectively1
 
 
 
Changes in Freelite® serum free light chain concentrations and clinical status in 6 patients with Nonsecretory Myeloma. NR= Upper limit of normal ranges.
 
Blood: journal of the American Society of Hematology Copyright 2001 by AMERICAN SOCIETY OF HEMATOLOGY (ASH). Reproduced with permission of AMERICAN SOCIETY OF HEMATOLOGY (ASH) in the format Internet posting via Copyright Clearnace Center.
 
 
 
 
 
 
 
 
 

Copyright 2004 Wiley. Used with permission from Alyanakian et al. American Journal of Hematology, Wiley Interscience. www.interscience.wiley.com

The serum Freelite® assay is sensitive enough for correlation with clinical events and is more sensitive than urine results.2
Alyanakian et al. concluded, "Immunonephelometric measurement of serum free light chains are a reliable method for follow up of patients with light chain secreting monoclonal gammopathies". Also that for cases featuring hardly measurable amounts of light chain in the urine "...the serum free light chain assay proved sensitive enough for correlation with clinical events".2
 

 

Measurement of serum free light chains with Freelite® has shown that 96% of patients with Intact Immunoglobulin Multiple Myeloma have an abnormal light chain concentration or abnormal kappa/lambda ratios.3 
Freelite® provides sensitive analysis and is a more accurate, faster marker of tumour kill than intact immunoglobulin.
 
 
Monitoring of a Myeloma patient using IgG κ and free κ. Electrophoresis gels are shown for each sample. CVAMP = cyclophosphamide, vincristine, adriamycin, melphalan, prednisolone: HDM: high dose melphalan and stem cell transplant.
 

 

The Freelite® serum free light chain assay can be used to detect disease progression in Intact Immunoglobulin Multiple Myeloma (IIMM) patients who at relapse switch to production of light chains only.
For some IIMM patients in remission, relapse is accompanied by a marked rise in monoclonal serum free light chains (FLC) with no associated increase in intact immunoglobulin concentrations. This phenomenon is known as light chain (LC) escape or Bence-Jones escape.4
 

A model of light chain escape in a hypothetical patient with IIMM. Dual plasma cell subsets are present at diagnosis producing either monoclonal intact immunoglobulin and FLC or FLC alone. In response to chemotherapy, intact immunoglobulin and serum FLC concentrations fall (FLC fall more rapidly due to their shorter half life). Disease relapse with light chain escape is associated with proliferation of the light chain only plasma cell clone but not the intact immunoglobulin producing clone. This leads to a marked rise in serum FLC but no associated change in the intact immunoglobulin concentration.

Why is it important to detect light chain escape early?

  • LC escape is associated with increased tumour growth5
  • LC escape is indicative of disease progression5
  • Patients with light chain escape may have a poorer prognosis4

Light chain escape and its detection may increase with:

  • Longer patient survival6
  • Modern therapies6
  • Use of Freelite® serum FLC assay is likely to improve detection rates6

Measurement of serum immunoglobulin concentrations will fail to identify LC escape. Without Freelite®, LC escape is only detectable by urine Bence Jones Protein (BJP) measurement. Mead et al. examined 11 patients identified as showing light chain escape; this was corroborated by urine results in 5 of the patients. However, in the other 6 patients the urine free light chains were unmeasurable.6

Case Study: Patient with IgA lambda paraprotein

This patient received Velcade and responded to treatment, both IgA and lambda FLC concentrations fell. Several months later IgA concentrations remained stable but Freelite® lambda FLC increased significantly, indicating LC escape.

This case highlights the importance of using Freelite® to monitor IIMM.

Courtesy of E. Liakopoulou, Christie Hospital, Manchester, UK.

More information on Light Chain Escape

Measurement of serum free light chains with Freelite® has been shown to follow clearly the course of disease whilst the monoclonal IgG kappa, detectable by immunofixation electrophoresis, remained unchanged.7
 

Changes in serum monoclonal proteins during the disease course of a patient with AL amyloidosis. M&P: melphalan & prednisolone; PBSCT: peripheral blood stem cell autograft; ESRF: end stage renal failure. (Courtesy of PN Hawkins)

 More information on AL amyloidosis

  1. Dispenzieri A, et al. International Myeloma Working Group guidelines for serum-free chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23:215-224
  2. Drayson M, et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma.Blood 2001; 97:9:2900-2902
  3. Alyanakian MA, et al. Free Immunoglobulin Light-Chain Serum Levels in the Follow-up of Patients With Monoclonal Gammopathies: Correlation With 24-hr Urinary Light-Chain Excretion. Am J Hematology 2004; 75:246-248
  4. Mead GP, et al. Serum free light chains for monitoring multiple myeloma.BJH 2004; 126:348-354
  5. Ayliffe, et al. Demonstration of changes in plasma cell subsets in multiple myeloma. Haematologica 2007; 92:1135-8
  6. Dawson MA, et al. Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains. Haematologica 2007; 92:143-144
  7. Mead, et al. Incidence of light chain escape in myeloma patients at relapse. Br J Haematol 2008; 141:98a
  8. Lachmann, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol 2003; 122:78-84