Kyle.qxp 6/3/08 15:11 Page 27
Haematological Malignancies
Serum Free Light Chain Assays – Their Role in Multiple Myeloma
a report by
Robert A Kyle
Professor of Medicine and Laboratory Medicine, Mayo Medical School, Rochester
Globally, multiple myeloma (MM) accounts for 0.8% of all cancer is overwhelmed.
12
Furthermore, samples need to be collected over a
deaths, with a survival rate of 50% of those enrolled in clinical trials.
1,2
period of 24 hours, then concentrated in the laboratory. This
It is the most common bone marrow cancer in Europe, with over procedure is inconvenient and time-consuming, and can be inaccurate.
77,000 patients undergoing treatment at any one time.
3
In the US,
MM is the second most common haematological malignancy, affecting Diagnostic Potential of Free Light Chain Assays
4.4/100,000 people per year, with a male to female ratio of 1.4:1.
4
The Early clinical studies for the SFLC assay were carried out in LCMM
pre-malignant condition to MM – monoclonal gammopathy of patients. In two studies, serum taken at the time of clinical
undetermined significance (MGUS) – is present in approximately 3% of presentation was analysed from 270 subjects and an abnormal SFLC
Caucasians over 50 years of age.
5
Approximately 1% of MGUS ratio was noted in every case.
13,14
Moreover, urine tests during
patients will progress to MM or a related malignant condition each chemotherapy may become normal, whereas serum analysis may
year.
6
MGUS is defined by a monoclonal immunoglobulin (Ig) remain abnormal, suggesting that the SFLC test has an increased
(M-protein) concentration of <30g/l, with the bone marrow containing sensitivity for residual disease. In this subset of patients, the SFLC assay
less than 10% plasma cells and the absence of lytic bone lesions, may not correlate with the 24-hour urine test. By definition, patients
anaemia, hypercalcaemia and renal insufficiency.
7,8
To make a with NSMM do not have detectable monoclonal protein by IFE in
diagnosis of MGUS, laboratories have traditionally used serum protein serum or in urine. Currently, diagnosis of NSMM is achieved through a
electrophoresis (PEL) to detect the presence of M-protein and to bone marrow examination and the presence of other features of MM.
characterise the type using immunofixation electrophoresis (IFE). In one study, 70% of 28 patients with NSMM showed an abnormal
However, 15–20% of MM patients have light chain MM (LCMM) SFLC ratio.
10
and 3% have non-secretory MM (NSMM), which have small
or undetectable amounts of measurable monoclonal protein in A more recent study evaluated five untreated patients with NSMM, all
their serum with PEL.
9–11
Highly sensitive serum free light chain of whom had abnormal SFLC concentrations.
15
The SFLC concentration
(SFLC) assays are now available for clinical use; they allow in NSMM patients is below the detectable limit of the PEL and IFE.
quantification of free lambda (λ) and kappa (κ) chains. This new assay Thus, these patients can be monitored by the SFLC assay rather than
provides clinicians with an additional method of predicting prognosis the previously used tests.
of MGUS.
The SFLC test also has a positive impact on the monitoring and
Laboratory Evaluation detection of amyloidosis (AL). AL is characterised by fibrils consisting
In patients with no measurable monoclonal protein in serum or urine of monoclonal light chains deposited in various organs and tissues. The
using the standard PEL test, SFLC assays are helpful. Unlike IFE, the concentration of circulating SFLC is in many cases too low to be
SFLC assay is quantitative and, therefore, is more precise. In some measured using PEL and IFE. However, in 90–95% of patients with AL,
cases, the bands produced in electrophoresis are not well defined and SFLC assays are able to quantify circulating monoclonal light
it can often be difficult to determine whether they indicate a low level chains.
11,16
The SFLC assay allows the assessment of haematological
of M-protein in the serum or show an oligoclonal variation. In this responses in patients with a low tumour burden. Moreover, a
situation, an additional testing system would be beneficial. SFLC assays combination of an abnormal SFLC assay or serum IFE analysis on serum
use polyclonal antibodies to measure the level of unbound κ and λ samples from AL patients was present in 109 of 110 patients.
15
The
light chains in the serum by nephelometry. Light chains produced by
the myeloma cells are either κ or λ. The result of the production of one
Robert A Kyle is a Professor of Medicine and Laboratory
SFLC and not the other will cause an abnormal κ–λ ratio. Normally, the
Medicine at the Mayo Medical School, Rochester,
ratio range is 0.26–1.65; however, if the level of free κ rises
Minnesota. He serves as Chairman of the International
abnormally, the ratio will be shifted above 1.65, and vice versa. The
Myeloma Foundation Scientific Advisory Board. Professor
Kyle is also Chairman of the Myeloma Committee of the
M-protein has traditionally been measured using protein
Eastern Cooperative Oncology Group, and a member of the
electrophoresis and IFE of a 24-hour urine collection. However, blood
Editorial Board of Leukemia. He is Secretary General of the
Inter-American Division of the International Society of
assays have clear advantages over urine tests from a physiological
Hematology (ISH). Dr Kyle has published over 380 articles
standpoint. SFLCs are cleared rapidly through the renal glomeruli and relating to haematology and oncology and another 600 abstracts and editorials. He has also
metabolised in the proximal tubules of the nephrons in the kidney. In
served as both a guest lecturer and a visiting professor throughout the world. He received his
MD with distinction from Northwestern University Medical School.
normal patients, little or no SFLC is released into the urine and the
level of SFLC has to increase many-fold before the absorption system
© TOUCH BRIEFINGS 2007 27
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