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Home> Clinical Education> Hematology> Patient Management Stage> Monitoring
Monitoring

Freelite® – Recommended for Monitoring Treatment & Disease

The International Myeloma Working Group guidelines recommend serial assessment with free light chain assays (Freelite®) for monitoring of AL amyloidosis and oligosecretory Multiple Myeloma. 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.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 treatment.
  • Freelite® is highly specific and sensitive for serum kappa and lambda free light chains.
  • Freelite® can be used to monitor the majority of Multiple Myeloma patients, including detection of light chain escape in Multiple Myeloma patients.
  • Freelite® provides early indication of response to treatment.
  • Freelite® has a sensitivity much greater than currently available urine assays.
  • Freelite® assay time is less than 20 minutes, facilitating rapid clinical decisions.

See below for monitoring by disease: 

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)
 

  • 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 (BARB?).
  • 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 effectively.1
Use image NSMM.jpg with legend; Changes in serum free light chain concentrations and clinical status in 6 patients with Nonsecretory Myeloma. NR= Upper limit of normal ranges
 

 

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 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 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

 

 
The serum Freelite® assay is sensitive enough for correlation with clinical events and is more sensitive than urine results2.
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
 

 

This patient received Velcade and responded to treatment, both IgA and lambda FLC concentrations fell.

Several months later IgA concentrations remained stable but 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.

Click here for further information on Light Chain Escape 

  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