Freelite & Hevylite
®
Together Freelite
& Hevylite provide
optimal detection
of monoclonal
gammopathies
®
Monoclonal Gammopathy
Monoclonal gammopathies are diseases
of the bone marrow and are associated
with monoclonal proliferation of plasma
cells. The most common monoclonal
gammopathy is malignant Multiple
Myeloma. The tumour products formed
are monoclonal immunoglobulins and / or
free light chains. These are secreted into
the serum and are surrogate markers of
tumour burden.
Laboratory testing plays an important
role at various patient management
stages:
Plasma cell
Lambda FLC
Kappa FLC
Intact
Immunoglobulin
Multiple Myeloma
~90% produce FLCs
Diagnosis - to confirm disease state
Prognosis - to predict patient outcomes
Monitoring - to measure response to treatment
FLCs = Free Light Chains
Light Chain
Multiple Myeloma
Only produce FLCs
Nonsecretory
Multiple Myeloma
~70% produce FLCs
AL amyloidosis
~80% produce FLCs
Freelite
• κ FLCs
• λ FLCs
• κ/λ FLC ratio
“
...The serum FLC assay in combination
with serum PEL and serum IFE is sufficient
to screen for pathological monoclonal
plasmaproliferative disorders other than AL,
which requires all the serum tests as well as
the 24-h urine IFE.
“
Freelite is a sensitive, specific marker of
kappa (κ) and lambda (λ) free light chains
(FLCs) in serum and provides quantitative
measurement of:
The International Myeloma Working Group Guidelines1
state that Freelite should be used for the diagnosis,
prognosis and monitoring of monoclonal gammopathies
including:
Freelite is a simple, polyclonal antibody
blood test, providing rapid and highly
sensitive results.
• Light Chain Multiple Myeloma (LCMM)
• Nonsecretory Multiple Myeloma (NSMM)
• Intact Immunoglobulin Multiple Myeloma (IIMM)
• Smouldering Multiple Myeloma (SMM)
• Solitary Plasmacytoma
• AL amyloidosis
• Monoclonal Gammopathy of Undetermined Significance
(MGUS)
Improve your accuracy in detecting monoclonal gammopathies
PEL = Protein Electrophoresis
FLCs = Free Light Chains
AL = AL amyloidosis
IFE = Immunofixation Electrophoresis
Hevylite
Hevylite quantifies the different light chain
types of each immunoglobulin class IgGκ, IgGλ, IgAκ, IgAλ, IgMκ and IgMλ.
The molecules are assessed in pairs
e.g. IgGκ/IgGλ to produce heavy/light
chain ratios; an abnormal ratio indicates
monoclonality.
Hevylite uniquely measures both
the involved and the uninvolved
immunoglobulin, giving useful information
about immunosuppression of the
uninvolved isotype e.g. IgAκ in an IgAλ
patient.
The Hevylite assay works by targeting epitopes between the heavy chain and
light chain constant regions. Ig’ indicates IgG, A or M
Hevylite analysis allows improved management of Multiple Myeloma patients
Freelite and Hevylite in Monoclonal Gammopathy testing
Diagnosis
SPE + Freelite
• Freelite is now a myeloma defining event*
• Freelite plus SPE is an efficient diagnostic screen
• Recommended to rule out myeloma kidney
Hevylite
• Baseline with appropriate Hevylite pair for monitoring
Prognosis
Monitoring
Freelite + Hevylite
• Provides risk stratification for MGUS and AL amyloidosis
• Are prognostic indicators in Myeloma,1, 2 AL amyloidosis,1 WM,3, 4 SMM5
Freelite
• dFLC improves serial monitoring
• Ratio helps define stringent CR
• Use when only free light chains detected - LCMM, NSMM, AL amyloidosis
• To detect light chain escape
Freelite + Hevylite
• Oligosecretory MM or low level <10g/L
• Difficult to measure monoclonal protein due to co-migration, diffuse bands
• Residual disease
• Clonal differences
SPE = Serum Protein Electrophoresis
MGUS = Monoclonal Gammopathy of Undetermined Significance
MM = Mutiple Myeloma
WM = Waldenström’s Macroglobulinaemia
SMM = Smouldering Mutiple Myeloma
CR = Complete Response
LCMM = Light Chain Multiple Myeloma
NSMM = Nonsecretory Multiple Myeloma
* Involved:uninvolved sFLC ratio ≥100 and involved Freelite≥100mg/L
Diagnosis
Use Freelite and Hevylite together
The IMWG guidelines recommend Freelite
for
the
diagnosis
of
monoclonal
gammopathies.1 The assay quantitatively
measures free light chains providing improved
accuracy compared to traditional methods.
Freelite should be used with SPE/CZE in the
initial testing of patients to detect monoclonal
gammopathies; this allows urine testing to be
used more selectively.6,7
A Hevylite result at diagnosis provides a
baseline value that is useful in monitoring
and prognosis.
SPE = Serum Protein Electrophoresis
CZE = Capillary Zone Electrophoresis
At Diagnosis
SPE/CZE and Freelite ratio
Positive
Type with IFE
Establish baseline with
relevant/appropriate
Hevylite pair
IFE = Immunofixation Electrophoresis
Negative
Suspect AL amyloidosis,
24hr urine
Establish Freelite
baseline
Optimising your Diagnostic Approach for Monoclonal Gammopathy Testing
A combination of SPE/CZE and Freelite is a clinically sensitive strategy for diagnosis of
monoclonal gammopathies.
Protocols
SPE alone
Serum IFE
SPE, serum IFE, urine IFE
SPE/CZE and Freelite
SPE/CZE, Freelite and serum IFE
*Myeloma
88
94
100
100
100
7
% of Paraproteins detected
AL amyloidosis7 LCMM8,9,10
66
74
94
96
97
* Myeloma is inclusive of 467 patients with MM (451), NSMM (4),
Plasma cell leukaemia (4), Osteosclerotic MM (1), and Indolent Myeloma (7).
Detect more monoclonal gammopathies with Freelite
SPE = Serum Protein Electrophoresis
CZE = Capillary Zone Electrophoresis
IFE = Immunofixation Electrophoresis
FLCs = Free Light Chains
n.d. = no data
LCMM = Light Chain Multiple Myeloma
NSMM = Nonsecretory Multiple Myeloma
40 - 57
n.d.
n.d.
100
100
NSMM11
0
0
0
68
68
2014 IMWG Guidelines for Diagnosis of Multiple Myeloma
New IMWG Criteria for MM diagnosis12
Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma
PLUS a myeloma defining event:
One or more biomarkers of malignancy:
• Clonal bone marrow plasma cells ≥60%
• Involved:uninvolved sFLC ratio ≥100*
• >1 focal lesion on MRI studies
OR
* Involved Freelite concentration must be >100mg/L
Evidence of end-organ damage that can be attributed
to the underlying plasma cell proliferative disorder:
• Hypercalcaemia
• Renal insufficiency
CRAB
features
• Anaemia
• Bone lesions
}
Freelite now forms part of the IMWG diagnostic criteria for MM. It is recommended
that patients meeting these criteria be treated for myeloma
sFLC = serum Free Light Chain
IMWG = International Myeloma Working Group
MRI = Magnetic Resonance Imaging
MM = Multiple Myeloma
Detect Myeloma Kidney early to increase the chance of renal recovery
New AKI
The majority of Multiple Myeloma
patients produce an excess of
monoclonal serum free light chains
(FLCs). Freelite quantifies these
potentially nephrotoxic FLCs enabling
a rapid initial investigation for
Myeloma Kidney (Cast Nephropathy).
The International Kidney and
Monoclonal Gammopathy Research
Group have developed a screening
algorithm for new unexplained AKI.13
A clonal FLC ≥500mg/L is indicative of
Cast Nephropathy in new unexplained
AKI.
They recommend Freelite plus
SPE for diagnosis of monoclonal
gammopathies in these patients.
Exclude myeloma kidney
Assessment for FLC clone*
No FLC clone
FLC clone
Clonal FLC ≥500 mg/L
Clonal FLC <500 mg/L
AKI of another
cause
Either
Probable FLC tubular
interstitial pathology
• Requires hematology work-up
• Initiation of disease-specific
treatment to reduce serum
FLC levels
Alternative monoclonal
FLC pathology
Incidental MGUS
• Requires renal biopsy
• Consider hematology work-up
*To exclude the presence of an intact monoclonal immunoglobin,
serum FLC assays should be combined with serum protein
electrophoresis.
If detected early, renal impairment due to Cast Nephropathy is reversible AKI = Acute Kidney Injury
FLCs = Free Light Chains
SPE = Serum Protein Electrophoresis
MGUS = Monoclonal Gammopathy of Undetermined Significance
Prognosis
MGUS risk stratification improves patient management
MGUS group
Low risk
Lowintermediate risk
Highintermediate risk
High risk
Criteria
Recommended follow-up
No risk factors
present
6 months initially & if stable,
follow up every 2-3 years or
when symptoms suggest a
plasma cell malignancy
Any one risk
factor present
Any two risk
factors present
All three risk
factors present
6 months initially, then
annually and upon any
change in the patient’s
clinical condition
To optimise counselling and followup, IMWG guidelines recommend
MGUS patients should be risk stratified
at diagnosis using Freelite (alongside
SPE/IFE).14 By identifying those at
low risk (~40%), Freelite saves time,
money and patient discomfort as fewer
clinic visits and tests are needed.
Hevylite pair suppression is also an
independent risk factor for MGUS
progression.15
Risk factors:
• Abnormal FLC ratio • Serum monoclonal protein >15g/L • IgA or IgM monoclonal protein type
Smouldering Multiple Myeloma
SMM patients with a serum involved/uninvolved free light chain ratio ≥816 (but <100) are considered
higher risk with poor prognosis. These patients should be monitored closely and may be considered
candidates for early treatment intervention.
SPE = Serum Protein Electrohoresis
IFE = Immunofixation Electrophoresis FLC = Free Light Chain
MGUS = Monoclonal Gammopathy of Undetermined Significance
SMM = Smouldering Mutiple Myeloma
IMWG = International Myeloma Working Group
AL amyloidosis
Freelite is an independent prognostic marker for overall survival in AL amyloidosis, alongside
cardiac biomarkers.17
“
Incorporation of serum FLC-diff [dFLC] into the
current staging system improves risk stratification for
patients with AL amyloidosis and will help develop
risk adopted therapies for AL amyloidosis17
“
Kaplan-Meier curves for overall survival (OS) based on
the new staging system incorporating 3 risk factors.
Risk factors:
cTnT ≥ 0.025 ng/mL
NT-ProBNP ≥ 1800 pg/mL
FLC-diff ≥ 180 mg/L
Stages:
Stage 1 = no risk factors
Stage 2 = 1 risk factor
Stage 3 = 2 risk factors
Stage 4 = 3 risk factors
IMWG guidelines recommend the use of Freelite in prognosis.1
Use Freelite to predict outcomes and identify those AL amyloidosis patients
who may benefit from closer monitoring or altered therapy IMWG = International Myeloma Working Group
FLCs = Free Light Chains
FLC-diff = dFLC = involved Free Light Chain minus uninvolved Free Light Chain
cTnT = cardiac Troponin-T
NT-ProBNP = N-terminal pro–B-type natriuretic peptide
Monitoring
Use Freelite and Hevylite together
Monoclonal protein
obvious
>10g/L
Monoclonal protein
difficult to measure
Free Light Chains only
Abnormal Freelite ratio
<10g/L
Monitor with Freelite dFLC
plus Hevylite/SPE/CZE
Monitor with Hevylite
and Freelite dFLC
Monitor with
Freelite dFLC
At Complete Response (CR)
Measure Freelite ratio
To define a
stringent CR
Measure Hevylite ratio
Residual
Disease detection
Use Freelite and Hevylite together:
•To quantitatively monitor patients with Multiple Myeloma
•When monoclonal protein cannot be measured accurately using electrophoresis
•To provide additional sensitivity for detection of residual disease
SPE = Serum Protein Electrophoresis
CZE = Capillary Zone Electrophoresis
dFLC = involved Free Light Chain minus uninvolved Free Light Chain
FLCs = Free Light Chains
Monitoring with Freelite
IMWG guidelines recommend
the polyclonal Freelite test
for quantitative monitoring of
AL amyloidosis, NSMM and
Oligosecretory Multiple Myeloma.1
Rapid response to therapy
A rapid decrease in λ sFLCs gives an earlier indication of response than
intact immunoglobulin SPE measurements in a patient with IgGλ IIMM.
Freelite has greater sensitivity than
urine protein electrophoresis and
overcomes the issue of patient noncompliance for providing urine
samples.
FLC half-life is 2-6 hours compared to IgG half-life (up to 21 days)
providing earlier indication of response to treatment.
dFLC is recommended to monitor response to treatment. The k/l FLC ratio
alone is not recommended due to fluctuations in the uFLC 1
IMWG = International Myeloma Working Group
NSMM = Nonsecretory Multiple Myeloma
LCMM = Light Chain Multiple Myeloma
VDD = Velcade, doxorubicin and dexamethasone
sFLCs = serum Free Light Chains
IIMM = Intact Immunoglobulin Multiple Myeloma
dFLC = involved Free Light Chain minus uninvolved Free Light Chain
SPE = Serum Protein Electrophoresis
Monoclonal protein <10g/L
Oligosecretory disease - Monitor with Hevylite
and Freelite
Freelite is recommended by IMWG guidelines
for monitoring Oligosecretory Multiple Myeloma
due to its high sensitivity compared to traditional
techniques.1, 18
This has enabled patients to access clinical trials
from which they were previously excluded.19
Freelite can be used to monitor 71% of IIMM with
oligosecretory disease.20
Hevylite may offer a much-needed alternative
monitoring tool in these “difficult to quantify”
oligosecretory MM patients.21 In addition, changes
in Hevylite ratio reflect response to therapy and
relapse.22
SPE has limited accuracy due to significant
variation below 10g/L.23
Freelite measures at mg/L levels and the Hevylite
assay is linear below 10 g/L monoclonal
protein.24
Use Freelite and Hevylite to accurately monitor patients with low
levels of monoclonal protein IMWG = International Myeloma Working Group
MM = Multiple Myeloma
IIMM = Intact Immunoglobulin Multiple Myeloma SPE = Serum Protein Electrophoresis
Capture Multiple Myeloma patients that are difficult to quantify
IgA monoclonal proteins may co-migrate
with other serum proteins
SPE is not linear and dye saturation leads to
underestimation of responses
These 14 co-migrating samples were difficult
to measure accurately but all had an abnormal
Hevylite ratio.
Monoclonal protein is 44.9g/L by SPE, however
total IgG is 64.9g/L.26
Around 40% of IgA monoclonal proteins cannot be
quantified accurately by SPE.
Using Hevylite overcomes this limitation and
improves patient monitoring.25
Underestimation by SPE makes it difficult to
monitor patients.
Hevylite provides an accurate numerical result.
Use Hevylite when electrophoresis is inaccurate SPE = Serum Protein Electrophoresis
Detect Light Chain Escape to improve patient outcome
Light Chain Escape (LCE) is an increase
in monoclonal free light chains at relapse
with no associated increase in intact
immunoglobulin concentrations.
Patients who relapse with any light chain
involvement have poorer prognosis
than those relapsing with intact
immunoglobulins only.27 Of relapsing
IgA MM patients, 20% have LCE and of
relapsing IgG patients ~7% have LCE.27
By detecting LCE early, unnecessary
complications such as renal impairment
may be avoided. 28
λ
Courtesy of Christie Hospital, Manchester, UK.
This Intact Immunoglobulin MM patient was
monitored following bortezomib treatment ( ). Both
IgAλ and λ serum FLC levels decrease in response
to treatment and remain stable for many months.
Subsequent relapse with LCE was only detected
by Freelite.
Monitor with Freelite to ensure that Light Chain Escape is not missed
MM = Multiple Myeloma
Identify patient clonal differences
Different plasma cell clones can produce serum FLCs and intact monoclonal immunoglobulins in
the same patient.29 This is an example of intra-clonal heterogeneity, which is increasingly prevalent
in myeloma.
Clones detected at relapse and progression can be different
to those seen at diagnosis.30
1.Light chain only patients showed no change
2.60% of patients with both intact immunoglobulins and FLCs
changed their monoclonal protein type
3.17% of patients with intact immunoglobulins changed their
monoclonal protein type
44% of the total number of patients changed their
monoclonal protein type at relapse (
).
1
2
3
Used together, Freelite and Hevylite can identify clonal differences
R/POD = Relapse/Progression of Disease
FLCs = Free Light Chains
CR = Complete Response
Use Freelite and Hevylite to capture clonal change
Freelite and Hevylite measure two independent biomarkers in Multiple Myeloma.
• Freelite measures kappa(k) and lambda(l) free light chains (mg/L)
• Hevylite measures intact monoclonal immunoglobulins (g/L)
This study of an MM patient
with IgAk monoclonal
proteins plus k free light
chains highlights why it
is important to monitor
patients with Hevylite and
Freelite.
The patient presented with abnormal
Hevylite and Freelite ratios. Following
treatment both the Hevylite ratio and
κFLC concentrations normalise.
kFLC = Kappa Free Light Chain
After more treatment the Hevylite ratio did not normalise.
Further relapse was seen at around 2000 days with both an
increase in the Hevylite ratio and κFLC concentration.
By day 900 the patient relapsed with an increase in IgA Hevylite
ratio but little change in the κFLC levels.
Freelite and Hevylite are
both quantitative and
easy to use, combining
accurate results with high
sensitivity, enabling rapid
identification of clonal
change at relapse.
Achieving Stringent Complete Response indicates better outcome following ASCT
Patients who achieve a sCR have a better
outcome compared to those with a lower depth
of response to treatment.31
Patients with a sCR after ASCT had a better
overall survival than those who achieved a CR.
Definition of sCR19, 32
•Normal Freelite ratio
• Negative SPE and IFE
• Disappearance of soft tissue plasmacytomas
• Absence of clonal plasma cells by IHC/2-4
colour flow cytometry
For measurable or immeasurable disease
Where the sCR was sustained for ≥6 months post
transplant, a significantly better overall survival
was achieved compared to when a sCR was not
sustained.
Freelite is essential for assessing sCR in all myeloma patients
SPE = Serum Protein Electrophoresis
IFE = Immunofixation Electrophoresis
ASCT = Autologous Stem Cell Transplant
IHC = Immunohistochemistry
CR = Complete Response
sCR = stringent Complete Response
Use Hevylite to capture more residual disease
AB C D E
SPE positive
SPE positive
SPE negative
SPE negative
SPE negative
The high sensitivity of Hevylite can
indicate the presence of residual
disease in patients classified as
being in Complete Response by
other methods (D).2
The abnormal Hevylite ratio in B-D
is produced by immunosuppression
of the uninvolved immunoglobulin
(IgAλ) rather than an increase in
the involved IgAκ, highlighting the
unique information provided by
Hevylite.
Red = abnormal Hevylite
Using Hevylite and Freelite together improves sensitivity when
detecting intact immunoglobulin monoclonal proteins and free light
chains in residual disease.2
More information for better patient care decisions
IF = Immunofixation Electrophoresis
SPE = Serum Protein Electrophoresis
HLC = Heavy / Light Chain
Key Terminology
Freelite
Description
Example in a Lambda
LCMM patient
Involved FLC
The FLC type produced by the tumour
l
uFLC
Uninvolved FLC
The alternate light chain type to the iFLC
k
k/l sFLC ratio
k/l
A ratio of the concentration of κ to λ sFLC
(indicates monoclonality)
k/l
dFLC
iFLC – uFLC
The difference in the concentration between the
iFLC and uFLC
l-k
Involved/
Uninvolved sFLC
ratio
iFLC/uFLC
A ratio of the concentration of involved to
uninvolved sFLC – could be κ/l or l/κ
l/k
Term
Definition
Description
Example in an
IgGk MM patient
HLC
Heavy and light chain
isotypes
iHLC
Involved HLC
The HLC type produced by the tumour
IgGk
uHLC
Uninvolved HLC
The same heavy chain isotype but alternate light
chain type to the iHLC
IgGl
HLC ratio
e.g. IgAk/IgAl
A ratio of the concentration of κ to λ HLC
(indicates monoclonality)
IgGk/IgGl
dHLC
iHLC – uHLC
For a particular immunoglobulin isotype, the
difference in concentration between the iHLC and
uHLC
IgGk-IgGl
HLC-pair
suppression
When the concentration
of the uHLC is below the
normal reference interval
The ratio must be abnormal
Suppression of IgGl
Term
Definition
FLC
Free Light Chain
iFLC
Hevylite
LCMM = Light Chain Multiple Myeloma
MM = Multiple Myeloma
Reference ranges
Hevylite
Freelite
Normal adult serum
95 percentile range
Normal adult
k FLC
3.30 - 19.40 (mg/L)
l FLC
5.71 - 26.30 (mg/L)
serum
IgG Kappa
k / l FLC ratio
100 percentile range
0.26 - 1.65
An abnormal k/l FLC ratio is a highly sensitive
indicator of monoclonal k or l FLC in serum.
A study showed that patients with renal
impairment had increased levels of FLC in
serum and proposed an extended Freelite
ratio reference range k/l FLC ratio: 0.37-3.1 for
these patients.33
Renal reference range
100 percentile range
k / l FLC ratio
0.37 - 3.1
The renal reference range improves specificity
whilst maintaining diagnostic sensitivity in
patients with renal impairment.
95 percentile range
for SPAPLUS®
3.84 - 12.07 (g/L)
IgG Lambda
1.91 - 6.74 (g/L)
IgGk/IgGl Ratio
IgA Kappa
1.12 - 3.21
0.57 - 2.08 (g/L)
IgA Lambda
0.44 - 2.04 (g/L)
IgAk/IgAl Ratio
0.78 - 1.94
IgM Kappa
0.19 - 1.63 (g/L)
IgM Lambda
0.12 - 1.01 (g/L)
IgMk/IgMl Ratio
1.18 - 2.74
Interpretation
Freelite and Hevylite should be used in conjunction with other laboratory tests and clinical evaluations.
Freelite results should be considered in the following categories:
• Normal samples. SPE + FLC results are normal - unlikely that the patient has a monoclonal gammopathy
• Abnormal k/l ratios. Possible monoclonal gammopathy - needs further investigation.
Borderline elevated k/l ratios occur with renal impairment and may require appropriate renal function tests
• Low concentrations of k, l or both indicate bone marrow suppression
• Elevated concentrations of both k and l with a normal k/l ratio may be due to:
- Renal impairment (common)
- Over-production of polyclonal FLC from inflammatory conditions (common)
- Biclonal gammopathies of different FLC types (rare)
• Elevated concentrations of both k and l with an abnormal k/l ratio:
Possible combination of monoclonal gammopathy and renal impairment
Hevylite for monitoring:
• Abnormal HLC ratio indicates monoclonality
• Abnormal HLC ratio + HLC pair suppression indicates poor prognosis
MG = Monoclonal Gammopathy
pIg = Polyclonal Immunoglobulin sFLC = serum Free Light Chain
HLC = Heavy / Light Chain FLC = Free Light Chains
SPE = Serum Protein Electrophoresis
Learn More
Quality Assurance
Our manufacturing site has quality systems approved to both ISO9001 and ISO13485 certification. These, together
with strict adherence to rigorous internal quality control procedures, ensure customers can be confident in the
quality of Binding Site products.
Assays for in vitro diagnostic use have been FDA cleared for the USA and CE marked for Europe. Performance of
our assays is regularly monitored by participation in a number of independent national and international quality
assurance schemes.
The Binding Site GmbH
Schwetzingen
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Hevylite book
The Binding Site France,
Grenoble
7th Edition,
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Guidelines
International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
Rajkumar SV, et al. Lancet Oncology 2014; 15:e538-e548
International Myeloma Working Group recommendations for global myeloma care.
Ludwig H, et al. Leukemia 2014; 28:981-992
New Criteria for Response to Treatment in Immunoglobulin Light Chain Amyloidosis Based on Free
Light Chain Measurement and Cardiac Biomarkers: Impact on Survival Outcomes.
Palladini, et al. J Clin Onc 2012; 30:4541-4549
Consensus recommendations for the uniform reporting of clinical trials: report of the International
Myeloma Workshop Consensus Panel 1.
Rajkumar SV, et al. Blood 2011; 117:4691-4695
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic)
multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for
monitoring and management.
Kyle RA, et al. Leukemia 2010; 24:1121-1127
International Myeloma Working Group guidelines for serum-free light chain analysis in multiple
myeloma and related disorders.
Dispenzieri A, et al. Leukemia 2009; 23:215-224
International uniform response criteria for multiple myeloma.
Durie BGM, et al. Leukemia 2006; 20:1467-1473
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367: 580-581.
2. Ludwig H, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and
monitoring, identify residual disease and correlate with survival in multiple myeloma patients.
Leukemia 2013, 27:213-219
21. Boyle E, et al. IgA Kappa/IgA Lambda Heavy/Light Chain Assessment in the Management of
Patients with IgA Myeloma. Cancer 2014;120:3952-3957
3. Itzykson R, et al. Serum-free light chain elevation is associated with a shorter time to treatment
in Waldenström’s Macroglobulinemia. haematologica 2008;93: 793-794
4. Leleu X, et al. Novel M-Component Based Biomarkers in Waldenström’s Macroglobulinemia.
CLML 2011;11: 164-167
5. Bhutani M, et al. Serum Heavy-Light Chains (HLC) and Free Light Chains (FLC) As Predictors
For Early CR In Newly Diagnosed Myeloma Patients Treated With Carfilzomib, Lenalidomide, and
Dexamethasone (CRd) 2013: Blood 122(21); 762a
6. Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem
Rev 2009; 30:105-11
7. Katzmann JA, et al. Screening Panels for Detection of Monoclonal Gammopathies. Clin Chem
2009; 55:1517-1522
8. Bradwell AR, et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet
2003; 361:489-491
9. Wolff F, et al. Assessment of the analytical performance and the sensitivity of serum free light
chains immunoassay in patients with monoclonal gammopathy. Clin Biochem 2007; 40:351-4
10. Abraham RS, et al. Correlation of Serum Immunoglobulin Free Light Chain Quantification
with Urinary Bence Jones Protein in Light Chain Myeloma. Clin Chem 2002; 48:655-657
11. Drayson M. et al. Serum free light-chain measurements for identifying and monitoring
patients with nonsecretory multiple myeloma. Blood 2001;97:2900-2902
22.Ludwig H, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and
monitoring, identify residual disease and correlate with survival in multiple myeloma patients.
Leukemia 2013; 27:213-219
23. Katzmann J, et al. Long-Term Biological Variation of Serum Protein Electrophoresis M-Spike,
Urine M-Spike, and Monoclonal Serum Free Light Chain Quantification: Implications for
Monitoring Monoclonal Gammopathies. Clin Chem 2011, 57: 1687-1692
24.Eckold J, et al. Analytical performance and diagnostic potential of immunoassays
determining Intact Immunoglobulin k/l ratios in monoclonal gammopathies. Clin Lab 2014;
60:1491-1500
25. Katzmann, J et al. Monitoring IgA Multiple Myeloma: Immunoglobulin Heavy/Light Chain
Assays. Clin Chem 2015; 61:360-367
26. Katzmann and Kyle. Manual of molecular and Clinical laboratory Immunology. 7th ed, ASM
press, Washington DC
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