Published by the IC
nternational M I
yeloma FT
oundation
ING
Special Edition: A S
SCO 2009
Serum Free Light Chain Assays 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, focused solely on Serum Free Light Chain Assays, a trademarked procedure known
commonly as the FreeliteTM test. The Binding Site is the company responsible for this incredibly useful tool that provides necessary
diagnostic information for multiple myeloma, amyloidosis, and other hematologic malignancies. This special edition corresponds with
the 2009 annual meeting of the American Society of Clinical Oncology (ASCO). In this CITINGS, we have highlighted a data presentation
from the ASCO meeting, and also provided references to the latest published journal articles on Serum Free Light Chain Assays from the past
six months.
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 www.myeloma.org.
Susie Novis, President, IMF
American Society of Clinical Oncology Presentation 2009
Saturday, May 30th
Prognostic value of stringent complete response (sCR) post-autologous stem cell transplant (SCT)
in multiple myeloma (MM).
P. Kapoor, S. Kumar, A. Dispenzieri, M. Q. Lacy, S. R. Hayman, F. K. Buadi, D. Dingli, P. R. Greipp,
S. V. Rajkumar, M. A. Gertz
J Clin Oncol 27:15s, 2009 (suppl; abstr 8587)
Lymphoma and Plasma Cell Disorders
Abstract No.: 8587
Session Type: General Poster
Poster No.: S17
Time: 8:00AM 12:00PM
Location: Level 2, West Hall C
The authors study 468 myeloma patients who had achieved at least a partial response post-SCT, using results of serum and urine
protein studies, serum free light chain (FLC) assay, and BM evaluation, including measurement of marrow plasma cell clonality
by immunohistochemistry obtained 60 days after SCT to determine the best response. The authors conclude that the step-wise
improvement in the response duration across nCR, CR and sCR highlights the contribution of immunofixation studies, marrow
assessment of clonality and FLC estimates.
Publication Only
sFLC in healthy Indian subjects and myeloma patients.
R. Kumar, D. Gupta, V. Raina, A. Sharma, L. Kumar, M. Irshad, S. Singh, A. Chopra
J Clin Oncol 27, 2009 (suppl; abstr e19565)
The authors report serum free light chain in Indian healthy subjects and myeloma patients. They conclude that healthy Indian
subjects have higher and values than reported, possibly because of greater incidence of subclinical infections. However /
range is comparable and iFLC >100mg/l appears uncommon. The / ratio is highly sensitive method for myeloma detection.
Results need validation in larger cohort of healthy subjects and patients.
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Funded by an unrestricted educational grant from The Binding Site.
Serum Free Light Chain Assays Publications from the past 6 months
NQuantitation of serum free light chains in combination with protein electrophoresis and clinical information for diagnosing
multiple myeloma in a general hospital population.
Piehler AP, Gulbrandsen N, Kierulf P, Urdal P.
Clin Chem. 2008 Nov;54(11):1823-30. [Epub 2008 Sep 18.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18801937?ordinalpos=56&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors find that the combined use of serum protein electrophoresis, serum free light chain measurements, and clinical criteria allows myeloma to be
efficiently diagnosed or excluded based on serum measurements only.
NSerum free-light chain removal by high cutoff hemodialysis: optimizing removal and supportive care.
Hutchison CA, Harding S, Mead G, Goehl H, Storr M, Bradwell A, Cockwell P.
Artif Organs. 2008 Dec;32(12):910-7.
:
http://www.ncbi.nlm.nih.gov/pubmed/19133018?ordinalpos=46&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
To optimize the removal of free light chains (FLCs) by a dialyzer, the authors study the effect of dialyzers in series, dialyzer change, and hemodiafiltration
in 14 patients with multiple myeloma and renal failure. They find that different protocols are required to optimize the removal of kappa and lambda FLCs
in patients with myeloma and renal failure.
NResolution of cast nephropathy following free light chain removal by haemodialysis in a patient with multiple myeloma:
a case report.
Basnayake K, Hutchison C, Kamel D, Sheaff M, Ashman N, Cook M, Oakervee H, Bradwell A, Cockwell P.
J Med Case Reports. 2008 Dec 9;2:380.
:
http://www.ncbi.nlm.nih.gov/pubmed/19068112?ordinalpos=45&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The observations of this single-patient study indicate that cast nephropathy can quickly resolve on rapid reduction of monoclonal serum free light chains.
This has important implications for the development of treatment strategies aimed at improving renal recovery rates for patients in this setting.
N5th International Symposium on clinical applications of serum free light chain analysis. [Article in French]
Decaux O.
Rev Med Interne. 2009 Jan;30(1):96-100. [Epub 2008 Dec 2.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19054596?ordinalpos=43&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
No abstract available.
NStaging multiple myeloma patients with active disease using serum levels of beta2m-free HLA class I heavy chain together
with IgM or platelet count.
Perosa F, Minoia C, Favoino E, Prete M, Dammacco F.
Blood Cells Mol Dis. 2009 Jan-Feb;42(1):71-6. [Epub 2008 Nov 7.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18996035?ordinalpos=35&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors investigate the possibility of stratifying patients with active disease according to serum beta-2-microglobulin (beta2m)-free heavy chains (FHC)
and other clinical parameters and conclude that the independent prognostic markers FHC, IgM and platelets provide two staging systems unaffected by
renal insufficiency; both are effective in evaluating myeloma patients with active disease.
NMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma: a prospective study.
Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R,
Rajkumar SV.
Blood. 2009 Jan 29. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19179464?ordinalpos=30&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
This study identifies 71 individuals who developed myeloma during the course of the study in whom serially-collected pre-diagnostic serum samples
obtained 2-9.8 years prior to myeloma diagnosis were available, with an asymptomatic MGUS stage preceding the diagnosis of myeloma in all cases. The
authors find that in about half the study population, the M-protein concentration and involved free light chain-ratio levels show a yearly increase prior to
myeloma diagnosis. The authors conclude that novel molecular markers are needed to better predict progression to myeloma in individuals with MGUS.
NInternational Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related
disorders.
Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Blade J, Lonial S, Dimopoulos M,
Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan
G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG;
International Myeloma Working Group.
Leukemia. 2009 Feb;23(2):215-24. [Epub 2008 Nov 20.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19020545?ordinalpos=28&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
This paper provides consensus guidelines for the use of the serum immunoglobulin-free light chain assay, an important assay in the diagnosis and manage-
ment of clonal related plasma cell disorders.
www.myeloma.org
(800) 452 - CURE (2873)
NSerum free light chain immunoassay as an adjunct to serum protein electrophoresis and immunofixation electrophoresis in
the detection of multiple myeloma and other B-cell malignancies.
Harding SJ, Mead GP, Bradwell AR, Berard AM.
Clin Chem Lab Med. 2009 Feb 9. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19203202?ordinalpos=24&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors conclude that the additional malignancies identified by serum free light chain analysis add support for its inclusion in the routine screening
protocol for B-cell malignancies.
NNovel renal replacement strategies for the elimination of serum free light chains in patients
with kappa light chain nephropathy.
Kleeberg L, Morgera S, Jakob C, Hocher B, Schneider M, Peters H, Rötzer S, Müller C, Kaiser M, Fleissner C, Heider U,
Neumayer HH, Sezer O.
Eur J Med Res. 2009 Feb 18;14(2):47-54.
:
http://www.ncbi.nlm.nih.gov/pubmed/19258212?ordinalpos=21&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors report about a highly efficient method to eliminate serum free light chain (sFLC) using a newly designed protein leaking membrane in patients
suffering from sFLC induced acute renal failure.
NA monoclonal gammopathy precedes multiple myeloma in most patients.
Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM.
Blood. 2009 Feb 20. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19234139?ordinalpos=20&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors cross-reference their autologous stem cell transplant database with the Department of Defense Serum Repository, performing serum protein
electrophoresis, immunofixation electrophoresis, and serum free light chain analysis on all sera collected two or more years prior to diagnosis to detect a
monoclonal gammopathy (M-Ig). They find that all four patients with light-chain/non-secretory myeloma evolved from a light-chain M-Ig, with a pre-existing
M-Ig present in most myeloma patients prior to diagnosis. They conclude that tight-chain detected M-Ig is a new entity that requires further study.
N`Light-chain escape-multiple myeloma'-an escape phenomenon from plateau phase: report of the largest patient series
using LC-monitoring.
Kühnemund A, Liebisch P, Bauchmüller K, zur Hausen A, Veelken H, Wäsch R, Engelhardt M.
J Cancer Res Clin Oncol. 2009 Mar;135(3):477-84. [Epub 2008 Sep 18.]
:
http://www.ncbi.nlm.nih.gov/pubmed/18802723?ordinalpos=17&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors find that early detection of light-chain escape-myeloma (LCE-MM) by means of serial serum free-light chain measurements may prevent
unnecessary complications, allows physicians to detect unusual relapse manifestations in the era of intensive and biological therapy options, and possibly
also permits improved treatment results in LCE-MM.
NIdentification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation
of serum and urine.
Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G,
Marini M, Graziani MS, Melzi D'Eril GV, Moratti R, Merlini G.
Clin Chem. 2009 Mar;55(3):499-504. [Epub 2009 Jan 8.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19131635?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors find that the identification of amyloidogenic light chains cannot rely on a single test and requires the combination of a commercially available
free-light chain assay with immunofixation of both serum and urine.
NStaging systems and prognostic factors as a guide to therapeutic decisions in multiple myeloma.
Kyrtsonis MC, Maltezas D, Tzenou T, Koulieris E, Bradwell AR.
Semin Hematol. 2009 Apr;46(2):110-7.
:
http://www.ncbi.nlm.nih.gov/pubmed/19389494?ordinalpos=10&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Since numerous myeloma prognostic factors have been identified, including age, performance status, serum albumin, beta(2)-microglobulin (beta(2)M),
lactate dehydrogenase (LDH), renal function, genetic factors, and serum free light chains or their ratio (sFLCR), the authors suggest that the International
Staging System, which is already highly prognostic, could potentially be improved with the addition of sFLCR and eventually LDH.
NThe relationship between the serum free light chain assay and serum immunofixation electrophoresis, and the definition
of concordant and discordant free light chain ratios.
Singhal S, Vickrey E, Krishnamurthy J, Singh V, Allen S, Mehta J.
Blood. 2009 May 1. [Epub ahead of print.]
:
http://www.ncbi.nlm.nih.gov/pubmed/19411633?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
The authors study 2648 serial samples from 122 IgG or IgA myeloma to explore the relationship between serum free light chain ratio SFLCR and serum
immunofixation electrophoresis. They conclude that additional studies are required to determine the temporal relationship between SFLCR normalization
and paraprotein clearance and that until then the role of SFLCR in defining response remains controversial.
www.myeloma.org
(800) 452 - CURE (2873)
(800)452-CURE (2873)
www.myeloma.org
www.myeloma.org
(800) 452 - CURE (2873)