Transcript Slide 1

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
Soft blood-forming tissue that
fills the cavities of bone
White Blood
Cells
(B
lymphocytes/
Plasma cells)
Platelets
Plasma Cells Produce Antibodies and
Light Chains
Kappa
Lambda
Antibodies are Made up of Heavy
Chains and Light Chains
Light Chains
Antibodies
Heavy Chains
Normal vs Myeloma
IgG κ
IgG L
IgA κ
IgA L
IgD κ
IgD L
IgE κ
IgE L
IgM κ
IgM L
Normal
Lots of different types of
whole antibodies
IgG κ
IgG L
IgA κ
IgA L
IgD κ
IgD L
IgE κ
IgE L
IgM κ
IgM L
IgG κ
IgG κ
Intact Ig Myeloma
Whole Ab and excess light
chains – and too many of both!
THERAPY
Myeloma Therapy
KILLS MYELOMA
CELLS
FEWER MYELOMA
CELLS = FEWER
ANTIBODIES AND
LIGHT CHAINS
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
Measured by
SPEP and IFE
Plasma Cell
Measured by
Serum free light
chain test =
Freelite
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
Normal Ranges for the Freelite
tests
Units
(mg/L)
Units (mg/dL)
Kappa:
Kappa:
3.3–19.4 mg/L
0.33–1.94 mg/dL
Lambda:
5.7–26.3 mg/L
Lambda:
0.57–2.63 mg/dL
k/l ratio:
k/l ratio:
0.26–1.65
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
Freelite Detects Response
Earlier than SPEP
300
60
250
50
200
40
150
30
100
20
50
10
0
0
1
Begin
Chemotherapy
10
15
50 200
Days
Kappa FLC
300
400
IgG (g/L)
Kappa FLC (mg/L)
FLC and IgG Levels During Treatment
500
IgG
Patient with IgG Kappa
Multiple Myeloma
Adapted from: Mead et al. BJH 2004 126:348
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
Freelite detects relapse earlier than
IFE
250
Lambda FLC (mg/L)
200
+
+
150
+
+
+
+
FLC
IFE
_
100
-
-
-
50
0
1
15
2
17
3
19
4
21
5
23
6
25
7
27
8
29
Months After Transplantation
Relapse: FLC levels start increasing 4 months before IFE
becomes positive.
Adapted from: Mosbaurer et al. Haematologica 2007:92:275
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, TBSUK
• Myeloma Canada summary
When you measure IgA
• You are measuring
• IgAk +IgAl
• (IgAk +IgAl)
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:
– IgAk v. IgAl
– IgGk v. IgGl
– IgMk v. IgMl
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