understanding serum free light chain (freelite®) and heavy chain-light chain (hevylite®) tests...
TRANSCRIPT
![Page 1: Understanding Serum Free Light Chain (Freelite®) and Heavy Chain-Light Chain (Hevylite®) Tests Judith A. Finlay Ph.D. Director of Scientific Affairs The](https://reader036.vdocument.in/reader036/viewer/2022062718/56649e6a5503460f94b673ad/html5/thumbnails/1.jpg)
Understanding Serum Free Light Chain (Freelite®) and Heavy Chain-Light
Chain (Hevylite®) Tests
Judith A. Finlay Ph.D.Director of Scientific Affairs
The Binding Site, Inc.San Diego, CA
Some of the subject matter and data contained or addressed in the following presentation may involve off-label or forward-looking use of Freelite® kits, Hevylite® kits and other Binding Site products. As such, no off-label use of Freelite, Hevylite or other Binding Site products can be supported by Binding Site Inc.
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Outline
• Background
• Tests used to Assess Multiple Myeloma
• Advantages of serum Free Light Chain Tests (Freelite®)
• Practical Considerations
• New Hevylite® tests
• Summary
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Multiple Myeloma: a cancer of the Plasma Cells
• Cancerous plasma cells accumulate in the bone marrow and cause symptoms:– Increased Infections– Kidney Damage– Anemia– Bone Damage
• Use Testing to monitor disease and guide therapy
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Plasma Cells are in the Bone Marrow
Red Blood Cells
White BloodCells (Blymphocytes/Plasma cells)
Platelets
Soft blood-forming tissue that fills the cavities of bone
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Plasma Cells Produce Antibodies and Light Chains
Kappa Lambda
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Antibodies are Made up of Heavy Chains and Light Chains
h
AntibodiesAntibodies
Heavy ChainsHeavy Chains
Light ChainsLight Chains
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Normal vs Myeloma
Lots of different types of whole antibodies
Whole Ab and excess light chains – and too many of both!
Normal
Intact Ig Myeloma
IgG κIgG LIgA κIgA LIgD κIgD LIgE κIgE LIgM κIgM L
IgG κ
IgG κIgG LIgA κIgA LIgD κIgD LIgE κIgE LIgM κIgM L
IgG κ
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THERAPY
KILLS MYELOMA CELLS
FEWER MYELOMA CELLS = FEWER
ANTIBODIES AND LIGHT CHAINS
Myeloma Therapy
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There Are Two Types Of Free Light Chains – Kappa And Lambda
Kappa Free Kappa Free Light ChainsLight Chains
Lambda Free Lambda Free Light ChainsLight Chains
The FreeLite Test Measures Free Light Chains
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Advantages of Freelite Tests
• Serum test specific for free light chains
• Very sensitive for detection of free light chains
• Early detection of response to treatment
• Earlier detection of relapse
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Tests Measure Antibodies and Light Chains
AntibodiesAntibodies
Free Light ChainsFree Light ChainsPlasma CellPlasma Cell
Measured by SPEP and IFE
Measured by Serum free light chain test = Freelite
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Advantages of Freelite Tests
• Serum test specific for free light chains
• Very sensitive for detection of free light chains
• Early detection of response to treatment
• Earlier detection of relapse
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Normal Ranges for the Freelite tests
Units (mg/L)
Kappa: 3.3–19.4 mg/L
Lambda: 5.7–26.3 mg/L
k/l ratio:0.26–1.65
Units (mg/dL)
Kappa: 0.33–1.94 mg/dL
Lambda: 0.57–2.63 mg/dL
k/l ratio:0.26–1.65
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Types of monoclonal proteins
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What type of MM do you have?
• Type of MM depends on type of abnormal protein found in blood or urine
• IgG kappa, IgG lambda, IgA kappa, IgA lambda• Light chain only (kappa or lambda)• Non-secretory (low to no protein)• Involved light chain: one that is elevated:
– E.g. IgG kappa, it is kappa• Determined by a combination of laboratory tests:
– SPE– sIFE– Freelite
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Why is your MM protein type important?
• If you have high levels of light chains you may be more prone to kidney damage
• If you are an IgA MM you will benefit most from the Hevylite test
• You will be able to tell if your MM protein type changes– E. g. Light chain escape can be detected
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Advantages of the Freelite Tests
• Serum test specific for free light chains
• Very sensitive for detection of free light chains
• Early detection of response to treatment
• Earlier detection of relapse
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Patient with IgG Kappa Multiple Myeloma
Adapted from: Mead et al. BJH 2004 126:348
Freelite Detects Response Freelite Detects Response Earlier than SPEPEarlier than SPEP
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Advantages of the Freelite Tests
• Serum test specific for free light chains
• Very sensitive for detection of free light chains
• Early detection of response to treatment
• Earlier detection of relapse
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+ + + + +
- - -
+
15 29272523211917
_
Relapse: FLC levels start increasing 4 months before IFE becomes positive.
Adapted from: Mosbaurer et al. Haematologica 2007:92:275
Freelite detects relapse earlier than IFE
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Monitoring Therapy with Serum Free Light Chains
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Advantages of the Freelite Tests
• Serum test specific for free light chains
• Very sensitive for detection of free light chains
• Early detection of response to treatment
• Earlier detection of relapse
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Lab Reports
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Units are important!May
July = 385 mg/L
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Practical Considerations for the Measurement of Serum Free Light
Chains
• Laboratory variability– Day to day variation in a lab– Normal lab to lab variation– Different chemistry instruments(Different kits for different instruments)
• Biologic variability
• Clinical changes are much greater
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Changing Laboratories
If you change the laboratory where your serum free light chains are measured:
– If possible, obtain some of the last sample and run it along with the new sample
– or– Establish a new baseline for your serum free light chain
levels– May note of units lab reports (mg/L or mg/dL)
The change in your absolute sFLC level should not effect the clinical interpretation
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Total Light Chain Assay“The total light chain assays are no longer used for diagnosis. Only FLC measurements have relevance” David Keren ASCP Press 2012
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Binding Site’s New Hevylite™ Tests
• Cleared by FDA• In studies in the USA• Early in tests’ development
– We expect these tests to add value to Freelite– We expect these tests to be especially helpful in
IgA MM patients• Durie and IMF has mentioned Hevylite• 2013 Publications: Mayo Clinic, Austria, TBS-
UK• Myeloma Canada summary
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When you measure IgA
• You are measuring
• IgAk +IgAl
• (IgA +IgA)
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IgG, A and M assays measure IgGk and IgGl, etc., together
IgGk IgGL IgAk IgAL IgMk IgML
Now IgAk and IgAl can be measured independently with Hevylite®Why is this important?
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What is HevyLite?
• Hevylite at test that measures the heavy and light chains together
• So what?• Can distinguish:
– IgA v. IgA – IgG v. IgG– IgM v. IgM
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Additional Resources
• www.wikilite.com (web version of our “red book”)
• Google “Binding Site”• Email us [email protected]• Call The Binding site 800-633-4484
– We have CESs & DSAs across the US and Europe
• Understanding Serum Free Light Chain Assays (IMF booklet)
• IMF website (myeloma.org)
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Summary
• Multiple Myeloma– cancer of the plasma cells– found in the bone marrow
• Plasma cells produce– Antibodies– free light chains
• Measure with lab tests– Including free light chain test (Freelite)– To monitor therapy
• Fewer light chains means fewer plasma cells
• New test for MM: Hevylite