Clinical interpretation of Serum
Free Light Chain assays
22 Feb 2013
Dr. Eric Chan
Consultant Immunologist
Queen Mary Hospital
Hong Kong
Figure 3.6. Diagrammatic representation of plasma cells producing
intact immunoglobulins with monomeric κ and dimeric λ FLC molecules.
(Serum Free Light Chain Analysis. AR Bradwell. 5th edition, 2008)
Clinical uses of serum free light chain (SFLC) assays

Screening of diseases with monoclonal gammopathy




Monitoring




SPE (serum protein electrophoresis) + SFLC provide a simple and effective
screen
Can replace SPE+UPE (urine protein electrophoresis)
UPE and serum IFE (immunofixation) can be ordered more selectively e.g.
for amyloidosis and for typing of myeloma respectively
Light chain multiple myeloma – potentially can replace 24-hour urine light
chain quantitation
Intact immunoglobulin multiple myeloma – for light chain escape
Non-secretory or oligo-secretory multiple myeloma
Prognosis


MGUS progression (monoclonal gammopathy with unknown significance)
IMWG guidelines:






Smouldering MM progression
plasmacytoma progression
Myeloma outcome
AL amyloidosis outcome
B-CLL outcome
Wald. Macro. outcome
1. LYC (F/59)






Breast carcinoma
Skull lesion ? Metastasis, biopsy: plasmacytoma
Bone marrow: plasma cell myeloma, Kappa restriction
SPE, UPE: no monoclonal detected (NMD)
IgG, A, M: immunosuppression
SFK ↑, SFL ↓
Discussion
1

Questions:
 Mis-match between UPE and SFLC?
 Light-chain Myeloma or Non-secretory Myeloma?

High SFK levels may be due to polymerisation. This results in an
over-estimation of the SFK level. Polymerisation would also
cause a false negative result in UPE because the polymerised
proteins are of different charges.

By definition this is non-secretory myeloma. There has been no
modification of the definition which is based on SPE/UPE/IFX.
But this patient is more likely to have LCMM.
2. CKY (M/58)

June 2005 – diagnosed Lambda light chain myeloma


BM - markedly hypercellular marrow for age. Sheets of abnormal plasma cells are seen.
Jan 2006 – post BMT BM: residual myeloma
Collect Date :
29/06/05
02/07/05 03/07/06 30/07/06 14/08/06
-----------------------------------------------------------------------------------------------------------------------------IgG
633 L
-767 L
776 L 1030
819 – 1725 mg/dl
IgA
61 L
-133
111
136
70 - 386 mg/dl
IgM
29 L
-68
86
156
55 - 307 mg/dl
SPE
Weak MD -NMD weak MD
weak MD
Serum IFX
free L
--weak GK
Total protein
66
--51.0
61.0
g/l
% Paraprotein
3
--4.2
5.2
%
Paraprotein
2
--2.1
3.2
g/l
S. Free Kappa
----21.90 H
3.30-19.40 mg/l
S. Free Lambda
----61.90 H
5.71-26.30 mg/l
S. K/L Ratio
----0.35
0.26-1.65
UPE
-MD
---Urine IFX
-FL
---Urine protein
-0.47
---<0.15 g/D
Urine % paraprotein -21%
---
Jul 2006 – weak IgG/K band -> oligoclonal reconstitution

Discussion



Weak monoclonal or oligoclonal responses are not uncommon when the bone marrow regenerates after
treatment by chemotherapy
Raised SFK and SFL, SFLC ratio normal
Renal function normal
2

Nov 2006 – relapse with

sheets of plasma cells in BM

But SFLC mildly elevated and UPE weak

Trephine biopsy shows markedly hypercellular marrow diffusely infiltrated by
abnormal plasma cells. Many show nuclear immaturity and prominent nucleoli.
Little erythroid and myeloid activity are recognised. Megakaryocytes are not seen.
Bony trabeculae are unremarkable. Reticulin fibres are moderately coarsened.
Discussion
2

Discrepancy between bone marrow and serological
findings (weak SPE or UPE bands, low SFLC levels,
but marked immunosuppression)

In general paraprotein levels reflect tumour load.
The tumour cells of this patient is oligo-secretory

3. HWM (M/53)
21/06/07
16/08/07
07/01/08
26/03/09
25/06/09
30/09/09
12/04/10
23/11/10
13,600
22.7
27.7
21.5
22.8
12.0
11.2
17.0
3.2
11.2
32.0
24.8
24.3
18.3
18.0
17.6
421.53
2.03
0.87
0.87
0.94
0.66
0.62
0.97
urea
6.7
6.7
3.5
7.5
6.7
5.6
7.6
6
creatinine
219
118
113
125
145
104
110
115
S Free Kappa
S Free Lambda
S K/L Ratio
Treatment
BM exam
VAD
pleomorphic
plasma cells
predominate
PBSCT
no p'cytosis
regenerating
marrow
mild p'cytosis
Questions & Discussion:
Reasons of ↑ SFK and SFL
•There is a mild degree of renal impairment. Hence both SFK
and SFL are elevated.
•Other causes: polyclonal activation
Normal ratio but still ↑SFK
•Although the ratio is normal the elevated SFK levels indicate
there is still residual disease
•Continuously falling indicates complete remission
"Serum free light chain measurement aids the diagnosis of myeloma in patients with severe
renal failure" BMC Nephrology 2008;9:11 doi: 10.1186/1471-2369-9-112
3
07/03/2011
05/09/2011
24/10/2011
26/04/2012
28/05/2012
12/10/2012
12/11/2012
S Free Kappa
26.1
34.3
53.5
182.0
82.0
190.0
435.0
S Free Lambda
52.5
31.4
26.8
39.9
23.5
17.4
21.6
S K/L Ratio
0.5
1.1
2
4.6
3.5
10.9
20.1
urea
5.6
6.3
6.1
5.1
10.2
7
5.7
creatinine
109
111
110
111
106
117
102
Treatment
BM exam
thal
Len/dx
no plasmacytosis
PET ++
Discussion:
↑ S Free Kappa and S Free Lambda with normal ratio initially
•Similar explanations as before
•Continuously rising S Free Kappa indicates relapse
Discrepancy between serum levels and bone marrow
•Bone marrow negative
•PET – extensive lytic lesions throughout the skeleton
no plasmacytosis
4. Light chain escape (TWF)
Collect Date :
26/10/07 26/10/07 06/12/07 26/12/07 15/01/08
-----------------------------------------------------------------------------------------------------------------------------IgG
-4870 H
1580
853
880
819 - 1725 mg/dl
IgA
-40 L
22 L
27 L
27 L
70 - 386 mg/dl
IgM
-23 L
19 L
14 L
14 L
55 - 307 mg/dl
B2M
-2.56 H
---< 1.42
ug/ml
SPE
-MD
MD
MD
MD
Serum IFX
-GL
---Total protein
-100.0
68.0
61.0
68.0
g/l
% Paraprotein
-27.5
18.8
9.9
8.3
%
Paraprotein
-27.5
12.8
6.0
5.6
g/l
UPE
MD
----Urine IFX
FL
----%Parapro.(Ur)
14.5
----%
2007 – present as IgG myeloma
2008-2009 – partial remission
4
Collect Date :
05/02/09 26/03/09 26/03/09 26/05/09 26/05/09
---------------------------------------------------------------------------------------------------------------------------------------IgG
--1190
-944
819 - 1725 mg/dl
IgA
--89
-54 L
70 - 386 mg/dl
IgM
--97
-59
55 - 307 mg/dl
SPE
% Paraprotein
---
---
WMD
WQ
UPE
%Parapro.(Ur)
NMD
--
NMD
--
---
----
----
S. Free Kappa
S. Free Lambda
S. Free K/L Ratio
0.64
127H
0.005
--MD
44.1
----
NMD
--
%
---
%
7.44
523H
0.014
retrospective assay
5/2009: Clinical deterioration
3.30-19.40 mg/L
5.71-26.30 mg/L
4
Collect Date :
12/08/09 20/08/09 28/08/09 28/09/09 27/10/09
------------------------------------------------------------------------------------------------------------------------IgG
--646 L
521 L
394 L
819 - 1725 mg/dl
IgA
--24 L
18 L
10 L
70 - 386 mg/dl
IgM
--28 L
21 L
15 L
55 - 307 mg/dl
SPE
Total protein
% Paraprotein
Paraprotein
-----
-----
MD
79.0
3.0
2.4
MD
68.0
3.0
2.0
MD
64.0
2.1
1.3
g/l
%
g/l
UPE
%Parapro.(Ur)
MD
88.2
---
---
---
---
%
----
----
----
S. Free Kappa
S. Free Lambda
S. K/L Ratio
IgG paraprotein levels stable
UPE & SFL increasing
6.86
5790
0.0012
----
3.30-19.40
5.71-26.30
mg/L
mg/L
4
Collect Date :
05/07/10
05/07/10 05/07/10 19/07/10 23/07/10
-----------------------------------------------------------------------------------------------------------------------------IgG
-267 L
-445 L
448 L
819 - 1725 mg/dl
IgA
-14 L
-35 L
37 L
70 - 386 mg/dl
IgM
-8L
-23 L
21 L
55 - 307 mg/dl
S. Free Kappa
--<1.07
--3.30-19.40 mg/L
S. Free Lambda
-->3000.00 H --5.71-26.30 mg/L
S. K/L Ratio
--<0.0004
--SPE
Total protein
% Paraprotein
Paraprotein
-----
UPE
%Parapro.(Ur)
MD
69.0
WMD
54.0
1.2
0.6
---
SFL continuously ↑ → death (2010)
-----
WMD
67.0
2.4
1.6
WMD
61.0
2.7
1.6
g/l
%
g/l
---
---
---
%
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