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Published by the IC
nternational M I
yeloma FT
oundation
INSG
pecial Edition: S
ASCO 2011
FreeliteTM / HevyliteTM Issue
The International Myeloma Foundation (IMF) presents this special edition of CITINGS, our premiere publication featuring the most
up-to-date information on myeloma treatment and supportive care. This edition focuses on the Freelite® test, an established immunoassay
panel that analyses free light chains, as well as the new HevyliteTM test, a novel immunoassay panel that analyses heavy chain/light chain
pairs, and references publications available since ASH 2010.
It is our hope that CITINGS will help keep you abreast of the latest developments in myeloma treatment. As always, we welcome your
feedback; you may contact the IMF at (800) 452-CURE (2873) or at our website myeloma.org.
Susie Novis, President, IMF
Serum Free Light Chain Assays Publications
November 2010 May 2011
NMonoclonal free light chains can be found in heavy chain diseases.
López-Anglada L, Puig N, Díez-Campelo M, Alonso-Ralero L, Barrena S, Aparicio MA, Gutiérrez NC, García-Sanz R.
Ann Clin Biochem. 2010 Nov;47(Pt 6):570-2. [Epub 2010 Oct 7.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20930031
This case report illustrates a new case of gamma-heavy chain disease, in which serum free light-chain analysis and flow cytometry represent a
valuable tool for diagnosis, a finding that could be very important for the future management of these patients.
Heavy chain diseases (HCDs) are rare B-cell lymphoproliferative neoplasias characterized by the production of a monoclonal component con-
sisting of a truncated monoclonal Ig heavy chain without the associated light chain. Among them, patients with gamma-HCD are so rare that
no more than 150 cases can be found in the literature. In this paper, we report one additional case: an 83-year-old man with a gamma-HCD,
in whom a kappa light chain component was detected in the serum by using the serum free light-chain assessment and in addition monoclonal
kappa cytoplasmic expression was detected in bone marrow plasma cells by flow cytometric analysis. In the work-up of the patient, the underlying
anatomopathological lymphoproliferative disease corresponded to a lymphoplasmacytic lymphoma, as it is stated in the current World Health
Organization classification (2008), with both lymphadenopathic and bone marrow infiltration. As in other cases, several autoimmune manifesta-
tions (antiphospholipidic syndrome and immune thrombocytopenia) were present during the course of the disease in this patient. This case report
illustrates a new case of gamma-HCD, in which serum free light-chain analysis and flow cytometry represented a valuable tool for diagnosis, a
finding that could be very important for the future management of these patients.
NCoexistence of myeloma cast nephropathy, light chain deposition disease, and non-amyloid fibrils in a patient
with multiple myeloma.
Qian Q, Leung N, Theis JD, Dogan A, Sethi S.
Am J Kidney Dis. 2010 Nov;56(5):971-6. [Epub 2010 Sep 25.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20870327
The authors describe the unusual kidney biopsy findings of concurrent myeloma cast nephropathy and glomerular non-amyloid fibrillary deposits
composed of immunoglobulin G heavy chains and light chains in a patient with multiple myeloma who presented with acute renal failure. They
show that laser microdissection and mass spectrometry is an extremely useful ancillary test for the diagnosis of heavy and light chain deposition
diseases.
Plasma cell dyscrasias can present as myeloma cast nephropathy, AL amyloid, or light chain deposition disease. We describe the unusual kidney
biopsy findings of concurrent myeloma cast nephropathy and glomerular non-amyloid fibrillary deposits composed of immunoglobulin G (IgG)
heavy chains and light chains in a patient with multiple myeloma who presented with acute renal failure. We performed laser microdissection
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and mass spectrometry-based proteomic analysis, which showed that the fibrillary deposits likely contained Ig1 constant region and light chain
constant region, whereas light chains and serum amyloid P proteins were absent. Treatment of multiple myeloma resulted in resolution of the
renal manifestations, suggesting a common underlying mechanism for the cast nephropathy and heavy and light chain deposition disease. We show
that laser microdissection and mass spectrometry is an extremely useful ancillary test for the diagnosis of heavy and light chain deposition diseases.
NSerum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with
clinical features.
Kumar S, Dispenzieri A, Katzmann JA, Larson DR, Colby CL, Lacy MQ, Hayman SR, Buadi FK, Leung N, Zeldenrust SR,
Ramirez-Alvarado M, Clark RJ, Kyle RA, Rajkumar SV, Gertz MA.
Blood. 2010 Dec 9;116(24):5126-9. [Epub 2010 Aug 26.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20798235
The authors study the relationship between free light chain (FLC) levels and clinical features in 730 patients with newly diagnosed amyloidosis
(AL). They find that the type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.
Immunoglobulin free light chains (FLC) are the precursors of amyloid fibrils in primary amyloidosis (AL). We studied the relationship between
FLC levels and clinical features in 730 patients with newly diagnosed AL. The plasma cell clone was lambda in 72% patients, and kappa in 28%
patients. kappa-AL had more GI tract and liver involvement, whereas renal involvement was more with lambda-AL. While the overall survival
(OS) was similar for kappa and lambda-AL, the median OS for those without an identifiable serum heavy chain was significantly shorter (12.6
vs. 29.9 months; P=0.02). The OS was shorter among those with a higher dFLC (involved FLC - uninvolved FLC; kappa>29.4 mg/dL or
lambda>18.2 mg/dL using median for cutoff); 10.9 vs. 37.1 months; P<0.001. In multivariate analysis, dFLC was independent of other prognos-
tic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.
NMass spectrometry-based proteomic diagnosis of renal immunoglobulin heavy chain amyloidosis.
Sethi S, Theis JD, Leung N, Dispenzieri A, Nasr SH, Fidler ME, Cornell LD, Gamez JD, Vrana JA, Dogan A.
Clin J Am Soc Nephrol. 2010 Dec;5(12):2180-7. [Epub 2010 Sep 28.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20876678
The authors describe the use of laser microdissection (LMD) and mass spectrometry (MS)-based proteomic analysis for the accurate typing of 14
cases of amyloidosis, as well as the clinicopathologic findings of four problematic cases of renal Ig heavy chain amyloidosis that required LMD/
MS proteomic analysis for accurate typing of the amyloid. They conclude that LMD/MS is a sensitive and specific tool for diagnosis and accurate
typing of renal amyloidosis, including Ig heavy chain amyloid.
BACKGROUND AND OBJECTIVES: Amyloidosis is a group of disorders characterized by accumulation of extracellular deposition of proteins
as insoluble aggregates. The clinical management of amyloidosis is based on identifying the underlying etiology and accurate typing of the amyloid.
Ig heavy chain amyloid involving the kidney is poorly recognized and often poses a diagnostic dilemma. DESIGN, SETTING, PARTICIPANTS,
& MEASURES: In this study, we describe the use of laser microdissection (LMD) and mass spectrometry (MS)-based proteomic analysis for the
accurate typing of 14 cases of amyloidosis. We also describe the clinicopathologic findings of four problematic cases of renal Ig heavy chain amy-
loidosis that required LMD/MS proteomic analysis for accurate typing of the amyloid. RESULTS: LMD/MS proteomic data of four cases of Ig
heavy chain renal amyloidosis showed Ig heavy chains with or without light chains. The break up of the Ig heavy chains was as follows: one case
showed Ig1 chain constant region and light chains, one case showed Ig chain constant region and light chains variable and constant regions,
whereas two cases showed Ig3 chain constant region and heavy chains variable region I and/or III without light chains. We compare the LMD/
MS proteomic data of Ig heavy chain renal amyloid with that of other types of amyloid, including Ig light chains, serum amyloid A, fibrinogen
A- chain renal amyloid, and transthyretin amyloid. CONCLUSIONS: We conclude that LMD/MS is a sensitive and specific tool for diagnosis
and accurate typing of renal amyloidosis, including Ig heavy chain amyloid.
NUse of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies.
Holding S, Spradbery D, Hoole R, Wilmot R, Shields ML, Levoguer AM, Doré PC.
Clin Chem Lab Med. 2011 Jan;49(1):83-8. [Epub 2010 Oct 20.]
:
http://www.ncbi.nlm.nih.gov/pubmed/20961192
The authors assess the effect of replacing urine protein electrophoresis (UPE) with serum free light chain (FLC) analysis and find that using
FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis, and hence treatment earlier in the disease for patients with
patients with monoclonal gammopathies.
Abstract Background: Serum free light chain (FLC) analysis is used in the prognostic assessment and monitoring of patients with monoclonal
gammopathies (MG). Its use in detection of MG is less widespread despite good sensitivity for diseases poorly detected by serum protein electro-
phoresis (SPE), e.g., FLC disease and AL amyloidosis. FLC analysis may facilitate earlier diagnosis in these diseases. However, if replacing urine
protein electrophoresis (UPE) in an initial screening algorithm, this must be balanced against any loss of detection of Bence Jones proteinuria
(BJP). Methods: We assessed the effect of replacing UPE with FLC. Sensitivity of FLC for BJP was assessed in 126 clinical cases where UPE and
FLC analyses were performed. Impact on disease detection was assessed from 753 patient sera tested by SPE and FLC and 128 patients matched
associated urine samples. Results: Sensitivity of FLC for BJP was 98%. Use of FLC in routine testing increased the number of MG detected by
7%. Conclusions: Using FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis and hence treatment earlier in the
patients' disease.
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NSixth International Symposium on clinical applications of serum free light chain analysis, Bath, England, 23-24 September
2010. [Article in French]
Decaux O.
Rev Med Interne. 2011 Jan;32(1):64-6. [Epub 2010 Dec 3.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21126805
No abstract available.
NSerum free light chain analysis in multiple myeloma and plasma cell dyscrasias.
Ozsan GH, Dispenzieri A.
Expert Rev Clin Immunol. 2011 Jan;7(1):65-73.
:
http://www.ncbi.nlm.nih.gov/pubmed/21162651
This article summarizes the recent studies and highlights the importance of free light chain analysis in the diagnosis of plasma cell dyscrasias,
its prognostic value, and its role in the management of this group of diseases.
After the development of a reliable method to detect free light chains in serum, several investigations have been conducted to explore their
importance in plasma cell dyscrasias (PCD). Detection of monoclonal proteins is very important in the diagnosis and management of PCD,
which include a broad spectrum of diseases such as multiple myeloma and also benign, premalignant disorders like monoclonal gammopathy of
undetermined significance. The aim of this article is to summarize the recent studies and to highlight the importance of free light chain analysis
in the diagnosis of PCD, its prognostic value and role in the management of this group of diseases.
NInterlaboratory study of free monoclonal immunoglobulin light chain quantification.
Vávrová J, Maisnar V, Tichý M, Friedecký B, Cermáková Z, Dastych M, Gottwaldová J, Kucera P, Krotká J, Racek J, Zenková J,
Schneiderka P, Lochman P, Zima T, Benáková H, Büchler T, Spácilová J, Hájek R, Palicka V.
Clin Chem Lab Med. 2011 Jan;49(1):89-92. [Epub 2010 Oct 29.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21034251
The authors initiate an interlaboratory study measuring free light chain (FLC) concentrations in 12 serum samples from patients with monoclonal
gammopathies. They find that, due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become
a part of the regular quality control cycle in myeloma centers.
Abstract Background: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice
for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum pro-
tein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. Methods: The
Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating
with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies.
Results: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements.
We found that repeatability depended more on the laboratory than on the device used for measurement. Conclusions: The study revealed several
weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with
values achieved in the NEQAS programme. Because the / ratio cannot be measured with high precision, and FLC concentrations should
be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part
of the regular quality control cycle in myeloma centres.
NNovel M-Component Based Biomarkers in Waldenström's Macroglobulinemia.
Leleu X, Koulieris E, Maltezas D, Itzykson R, Xie W, Manier S, Dulery R, Boyle E, Gauthier J, Poulain S, Tatiana T, Panayiotidis P,
Bradwell AR, Harding S, Leblond V, Kyrtsonis MC, Ghobrial IM.
Clin Lymphoma Myeloma Leuk. 2011 Feb 1;11(1):164-7.
:
http://www.ncbi.nlm.nih.gov/pubmed?term=hevylite
The authors summarize studies conducted to delineate the role of the Freelite® test and the Hevylite test® in Waldenstrom's macroglobulinemia.
Waldenstrom's macroglobulinemia (WM) is an indolent B-cell lymphoma of the lymphoplasmacytic type accompanied by a serum IgM com-
ponent. However, conventional IgM quantification lacks sensitivity, does not precisely reflect tumor burden of WM, and, although being the
main marker for monitoring response to treatment, may not be accurate. New serum M-component based biomarkers were developed for routine
practice in recent years, such as the Freelite® test and more recently the Hevylite® test. Studies have shown that Freelite was a prognostic marker
for time to treatment in WM that helps monitoring disease response or progression. Hevylite measures IgM-kappa and IgM-lambda, separately,
and might provide true quantitative measurement of the IgM M-spike. Although current data are preliminary, Hevylite might replace the current
technique to measure IgM M-spike in the years to come. We summarize herein studies conducted to delineate the role of these tests in WM.
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NRenal failure in multiple myeloma: a medical emergency.
Wirk B.
Bone Marrow Transplant. 2011 Feb 21. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21339749
The authors discuss newly diagnosed plasma cell myeloma, including that the serum free light chain assay and serum -2-microglobulin free
heavy chain assay are now being used to rapidly diagnose plasma cell myeloma in renal failure and provide prognostic information in the setting
of renal failure where the Durie-Salmon and International Staging Systems do not.
Up to 50% of newly diagnosed plasma cell myeloma (PCM) patients can present with renal insufficiency, 20% with severe renal impairment
and 10% requiring dialysis. PCM patients account for 2% of the dialysis population, adding 5000 new patients each year worldwide. Dialysis-
dependent PCM patients have a 2.77 higher risk of death compared with other dialysis-dependent patients without this diagnosis. Renal failure
and especially dialysis dependency is an independent poor prognostic factor in PCM, with the majority unable to achieve dialysis independence.
Renal failure in PCM is a medical emergency with the need for rapid accurate diagnosis and prompt institution of supportive care and PCM-
directed therapy, because reversal of renal impairment and recovery from dialysis dependency can occur in up to half the patients early in the
course of disease and can lead to enormous survival benefits. Recently, the serum free light chain (SFLC) assay and serum -2-microglobulin free
heavy chain (SFHC) assay have been used to rapidly diagnose PCM in renal failure and provide prognostic information in the setting of renal
failure where the Durie-Salmon and International Staging Systems do not. A renal biopsy early in the course of renal impairment can provide
diagnostic and prognostic information. A new generation of dialyzers with larger pores than routine dialyzers can be used with extended hemodi-
alysis to remove SFLC more efficiently than plasmapheresis, allowing for greater renal recovery. Novel chemotherapy agents such as bortezomib
are associated with an improved renal response and have moved to the front line of therapy. Successful use of high-dose therapy and autologous
hematopoietic cell transplantation (HCT) in PCM with renal failure and even dialysis dependency has been associated with late renal recovery
and also allowed for the subsequent use of renal transplantation to provide even greater survival benefits. Combined non-myeloablative allogeneic
HCT with renal transplant in PCM patients with end-stage renal disease on dialysis is now being studied in prospective trials.
NTransplantation vs. conventional-dose therapy for amyloidosis.
Palladini G, Merlini G.
Curr Opin Oncol. 2011 Mar;23(2):214-20.
:
http://www.ncbi.nlm.nih.gov/pubmed/21178616
This review focuses on the role of autologous stem cell transplantation and conventional-dose therapy in light of advances in risk stratification
and amyloidosis patient monitoring. Among the recent findings discussed is that the possibility of directly measuring the amyloidogenic precur-
sor, the circulating free light chain, improves monitoring response to therapy.
PURPOSE OF REVIEW: Multiorgan involvement renders patients with AL amyloidosis particularly susceptible to treatment toxicity. The
introduction of autologous stem cell transplantation (ASCT) represented a major advancement, but was associated with unacceptable toxicity in
high-risk patients. Thus, efforts were made to improve the eligibility criteria for ASCT and to design novel, more effective, conventional-dose
regimens. This review focuses on the role of ASCT and conventional-dose therapy in light of advances in risk stratification and patient monitor-
ing. RECENT FINDINGS:
The possibility of directly measuring the amyloidogenic precursor, the circulating free light chain (FLC), improved monitoring response to
therapy. Cardiac biomarkers, N-terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins (cTn) allow the most accurate prognostic
stratification and direct the choice of therapy. Serial measurement of NT-proBNP, cTn and FLC are used to rapidly assess treatment efficacy.
Bortezomib and immune-modulatory drugs are going to play a major role in conventional-dose therapy and as adjuvant treatment after ASCT.
SUMMARY: The choice between ASCT and conventional-dose chemotherapy is based on accurate risk assessment. Tight monitoring of hema-
tologic and cardiac response is the cornerstone of treatment. Upcoming randomized trials will redefine the role of available therapies, assisting in
the choice of the growing number of active regimens.
NA novel approach for the purification and proteomic analysis of pathogenic immunoglobulin free light chains from serum.
Lavatelli F, Brambilla F, Valentini V, Rognoni P, Casarini S, Di Silvestre D, Perfetti V, Palladini G, Sarais G, Mauri P, Merlini G.
Biochim Biophys Acta. 2011 Mar;1814(3):409-19. [Epub 2011 Jan 4.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21215335
The authors develop an immunopurification approach to isolate serum free light chains (FLC) from patients with monoclonal gammopathies, fol-
lowed by proteomic characterization. They conclude that this method is a novel instrument for studying the molecular bases of FLC pathogenicity,
allowing for the first time the punctual biochemical description of the circulating forms.
An excess of circulating monoclonal free immunoglobulin light chains (FLC) is common in plasma cell disorders. A subset of FLC, as amy-
loidogenic ones, possess intrinsic pathogenicity. Because of their complex purification, little is known on the biochemical features of serum FLC,
possibly related to their pathogenic spectrum. We developed an immunopurification approach to isolate serum FLC from patients with mono-
clonal gammopathies, followed by proteomic characterization. Serum monoclonal FLC were detected and quantified by immunofixation and
immunonephelometry. Immunoprecipitation was performed by serum incubation with agarose beads covalently linked to polyclonal anti- or
FLC antibodies. Isolated FLC were analyzed by SDS-PAGE, 2D-PAGE, immunoblotting, mass spectrometry (MS). Serum FLC were immuno-
precipitated from 15 patients with AL amyloidosis (serum FLC range: 98-2350mg/L), 5 with AL amyloidosis and 1 with light chain (LC)
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myeloma ( FLC range: 266-2660mg/L), and 3 controls. Monoclonal FLC were the prevalent eluted species in patients. On 2D-PAGE, both
and FLC originated discrete spots with multiple pI isoforms. The nature of eluted FLC and coincidence with the LC sequence from the bone
marrow clone was confirmed by MS, which also detected post-translational modifications, including truncation, tryptophan oxidation, cysteinyl-
ation, peptide dimerization. Serums FLC were purified in soluble form and adequate amounts for proteomics, which allowed studying primary
sequence and detecting post-translational modifications. This method is a novel instrument for studying the molecular bases of FLC pathogenicity,
allowing for the first time the punctual biochemical description of the circulating forms.
NChanges in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following
therapy in primary amyloidosis.
Kumar SK, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Tan T, Sinha S, Leung N, Kyle RA, Rajkumar SV,
Gertz MA.
Am J Hematol. 2011 Mar;86(3):251-5. doi: 10.1002/ajh.21948. [Epub 2011 Feb 15.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21328431
This current study supports the notion that free light chain (FLC) response is a more useful measure of hematological response than M-protein
response. It also highlights the importance of achieving at least a 90% reduction in the uninvolved FLC to improve the outcome of patients with
light-chain amyloidosis.
Current response criteria for light-chain amyloidosis (AL) relegate FLC response to a subsidiary status relative to serum M-protein response. Given
that light chains form the substrate for amyloid fibril formation, we hypothesized that changes in FLC might better predict outcome compared
to changes in intact immunoglobulin levels. Two patient cohorts were studied, 347 patients who underwent an autologous stem-cell transplant
(SCT) and 96 patients treated with melphalan/dexamethasone. We identified the lowest value following therapy for intact serum M-protein and
the difference between involved and uninvolved FLC (FLC-diff). We first examined the relative contribution of M-protein and FLC-diff on
the overall survival (OS), and found that FLC reduction, rather than M-protein reduction, significantly impacted OS. The median OS was not
reached among those with a 50% decrease in FLC-diff compared to 20 months for the remainder. On regression analysis, a 90% reduction in
FLC-diff following SCT best predicted being alive at 3 or 5 years. The median OS among those with a 90% decrease was not reached compared to
37.4 months for the rest P < 0.001. The current study supports the notion that FLC response is a more useful measure of hematological response
than M-protein response. It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of
patients with light-chain AL.
NSerial serum free light chain measurements do not detect changes in disease status earlier than electrophoretic M-spike
measurements in patients with intact immunoglobulin myeloma.
Uljon SN, Richardson PG, Schur PH, Anderson KC, Tanasijevic MJ, Lindeman NI.
Clin Chim Acta. 2011 Mar 18;412(7-8):562-8. [Epub 2010 Dec 7.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21144845
In this study, the authors find that with 16 of 17 intact immunoglobulin myeloma patients tested frequently over approximately 3 years, serum
free light chains perform no better than M-spike and do not add value to conventional serum electrophoresis.
BACKGROUND: Serum free light chains (SFLC) are used to manage patients with light chain or hyposecretory myeloma, and may also be useful
in patients with intact immunoglobulin myeloma (IIMM), because their shorter half-life may enable earlier indication of relapse/response than
electrophoretic M-spikes or heavy chain (IgGA) immunonephelometry. METHODS: One thousand five SFLC, M-spike, and IgGA concentra-
tions were compared at multiple time points during the treatment of 17 myeloma patients, followed over 7.7-63.4months. Changes in these
analytes were evaluated in context with changes in disease status and treatment. RESULTS: 14/17 (82%) patients showed synchrony between
M-spike, IgGA, and SFLC measurements. SFLC changes preceded M-spike/IgGA in 1 patient, and lagged behind M-spike/IgGA in 2 patients.
In eight patients, SFLC showed short-term fluctuations unaccompanied by changes in M-spike, IgGA, or clinical treatment. CONCLUSIONS:
In 16/17 intact immunoglobulin myeloma patients tested frequently over ~3years, SFLC performed no better than M-spike and did not add
value to conventional serum electrophoresis.
NImmunoglobulin free light chain dimers in human diseases.
Kaplan B, Livneh A, Sela BA.
ScientificWorldJournal. 2011 Mar 22;11:726-35.
:
http://www.ncbi.nlm.nih.gov/pubmed/21442150
This review focuses on the disease-related changes of the structure and level of dimeric free light chains, and raises the questions regarding their
formation, function, and role in the pathogenesis and diagnosis of human diseases.
Immunoglobulin free light chain (FLC) kappa () and lambda () isotypes exist mainly in monomeric and dimeric forms. Under pathological
conditions, the level of FLCs as well as the structure of monomeric and dimeric FLCs and their dimerization properties might be significantly
altered. The abnormally high fractions of dimeric FLCs were demonstrated in the serum of patients with multiple myeloma (MM) and primary
systemic amyloidosis (AL), as well as in the serum of anephric patients. The presence of tetra- and trimolecular complexes formed due to dimer-
dimer and dimer-monomer interactions was detected in the myeloma serum. Analysis of the amyloidogenic light chains demonstrated mutations
within the dimer interface, thus raising the possibility that these mutations are responsible for amyloidogenicity. Increased monomer and dimer
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levels, as well as a high / monomer ratio, were typically found in the cerebrospinal fluid from patients with multiple sclerosis (MS). In many
MS cases, the elevation of FLCs was accompanied by an abnormally high proportion of dimers. This review focuses on the disease-related
changes of the structure and level of dimeric FLCs, and raises the questions regarding their formation, function, and role in the pathogenesis and
diagnosis of human diseases.
NRegarding the Overestimation of Serum {kappa} Free Light Chains.
Levinson SS.
Clin Chem. 2011 May;57(5):775-7. [Epub 2011 Feb 8.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21303911
No abstract available.
NThe role of serum immunoglobulin free light chain in response and progression in waldenstrom macroglobulinemia.
Clin Cancer Res. 2011 May 1;17(9):3013-8. [Epub 2011 Mar 17.]
Leleu X, Xie W, Bagshaw M, Banwait R, Leduc R, Roper N, Weller E, Ghobrial IM.
:
http://www.ncbi.nlm.nih.gov/pubmed/21415221
The authors seek to examine the role of serum free light chain (sFLC) in response and progression of patients with Waldenstrom macroglobulin-
emia and find that involved sFLC may be a useful marker of tumor measurement, showing earlier response and progression compared with IgM
or M-spike measurements.
Introduction: The serum free light chain (sFLC) has been widely used in the assessment of response in patients with multiple myeloma and other
plasma cell dyscrasias. However, its use in Waldenstrom macroglobulinemia (WM) has not been previously assessed. We sought to examine the
role of sFLC in response and progression of patients with WM. Methods: This study was conducted in a cohort of 48 patients with a diagnosis
of WM, untreated (n = 20) or relapsed/refractory (n = 28), prospectively treated on a bortezomib and rituximab trial. RESULTS: Involved FLC
(iFLC) response occurred in 79% patients versus 60% by M-spike protocol criteria. The median time to response was shorter with iFLC than per
protocol (2.1 and 3.7 months; P = 0.05). Progression defined using iFLC also correlated well to progression in the protocol ( = 0.63). However,
the median time to progression (TTP) was more rapid by iFLC than per protocol (13.7 and 18.9 months). We also confirmed that a flare in
iFLC in post-rituximab therapy did not correlate with lack of response or shorter TTP. CONCLUSION: Involved sFLC may be a useful marker
of tumor measurement, showing earlier response and progression compared with IgM or M-spike measurements.
NAtypical imaging feature of Non-secretory multiple myeloma.
Neeravari A, Netravati P, Mohammed R, Ragupathi AR, Nagarajappa AH.
Ann Diagn Pathol. 2011 May 3. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/21546295
The authors describe the case of a 23 year-old female with a rare case of non-secretory myeloma, presenting with bilateral limb weakness of two
years duration. They find, in treatment, that free light chain assay (FLC) when used in complement with protein electrophoresis (PEP) and immu-
nofixation electrophoresis (IFE) are pivotal in diagnosis of non-secretory multiple myeloma or light chain myelomas; FLC is a useful monitoring
tool because it reflects therapy results due to short serum half-life.
Non-secretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma in which no monoclonal gammopathy can be
demonstrated in the serum or urine. We describe a rare case of non-secretory multiple myeloma in a 23 year old female presenting with bilateral
limb weakness of two years duration. Clinically she was diagnosed to have Pott's spine and was treated with category 1 anti-tubercular drugs.
Hematological investigations showed plasmacytosis and radiography showed osteolytic lesions. No monoclonal gammopathy was found in the
serum or urine. MRI showed multiple compressions with sclerosis within vertebral bodies suggestive of osteomalacia/diffuse infiltrative disorder.
The free light chain (FLC) assay revealed increment in the free kappa light chain and an abnormal / ratio. Free Light Chain assay (FLC) when
used in complement with Protein Electrophoresis (PEP) and Immunofixation Electrophoresis (IFE) were pivotal in diagnosis of non-secretory
multiple myeloma or light chain myelomas. FLC is a useful monitoring tool because it reflects therapy results due to short serum half-life.
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