Understanding Serum Free Light Chain (Freelite®) and Heavy ... lwm/ppt pdf/finlay... · Kappa FLC...
Transcript of Understanding Serum Free Light Chain (Freelite®) and Heavy ... lwm/ppt pdf/finlay... · Kappa FLC...
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.
Outline
• Background • Tests used to Assess Multiple Myeloma • Advantages of serum Free Light Chain
Tests (Freelite®) • Practical Considerations • New Hevylite® tests • Summary
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
Plasma Cells are in the Bone Marrow
Red Blood Cells
White Blood Cells (B lymphocytes/ Plasma cells)
Platelets
Soft blood-forming tissue that fills the cavities of bone
Plasma Cells Produce Antibodies and Light Chains
Kappa Lambda
Antibodies are Made up of Heavy Chains and Light Chains
Antibodies
Heavy Chains
Light Chains
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 κ IgG L IgA κ IgA L IgD κ IgD L IgE κ IgE L IgM κ IgM L
IgG κ
IgG κ IgG L IgA κ IgA L IgD κ IgD L IgE κ IgE L IgM κ IgM L
IgG κ
THERAPY
KILLS MYELOMA CELLS
FEWER MYELOMA CELLS = FEWER ANTIBODIES AND
LIGHT CHAINS
Myeloma Therapy
There Are Two Types Of Free Light Chains – Kappa And Lambda
Kappa Free Light Chains
Lambda Free Light Chains
The FreeLite Test Measures Free Light Chains
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
Tests Measure Antibodies and Light Chains
Antibodies
Free Light Chains Plasma Cell
Measured by SPEP and IFE
Measured by Serum free light chain test = Freelite
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
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
Types of monoclonal proteins
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
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
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
0 10 20 30 40 50 60
0 50
100 150 200 250 300
1 10 15 50 200 300 400 500
IgG
(g/L
)
Kap
pa F
LC (m
g/L)
Days
FLC and IgG Levels During Treatment
Kappa FLC IgG
Begin Chemotherapy
Patient with IgG Kappa Multiple Myeloma
Adapted from: Mead et al. BJH 2004 126:348
Freelite Detects Response Earlier than SPEP
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
+ + + + +
- - -
0
50
100
150
200
250
1 2 3 4 5 6 7 8
Lam
bda
FLC
(mg/
L)
Months After Transplantation
FLC IFE
+
15 29 27 25 23 21 19 17
_
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
Monitoring Therapy with Serum Free Light Chains
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
Lab Reports
Units are important! May
July = 385 mg/L
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
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
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
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
When you measure IgA
• You are measuring • IgAk +IgAl • (IgAκ +IgAλ)
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?
What is HevyLite? • Hevylite at test that
measures the heavy and light chains together
• So what? • Can distinguish:
– IgAκ v. IgAλ – IgGκ v. IgGλ – IgMκ v. IgMλ
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)
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