1. Clinical interpretation of Serum
Free Light Chain assays
22 Feb 2013
Dr. Eric Chan
Consultant Immunologist
Queen Mary Hospital
Hong Kong

2. 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)

3. Clinical uses of serum free light chain (SFLC) assays
 Screening of diseases with monoclonal gammopathy
 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
 Monitoring
 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

4. 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 ↓

5. Discussion
 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.
1

6. 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

7.  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.
2

8. Discussion
 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
2

9. 21/06/07 16/08/07 07/01/08 26/03/09 25/06/09 30/09/09 12/04/10 23/11/10
S Free Kappa 13,600 22.7 27.7 21.5 22.8 12.0 11.2 17.0
S Free Lambda 3.2 11.2 32.0 24.8 24.3 18.3 18.0 17.6
S K/L Ratio 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
Treatment VAD PBSCT
BM exam pleomorphic
plasma cells
predominate
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
3. HWM (M/53)

10. "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

11. 07/03/201
1
05/09/2011
24/10/201
1
26/04/201
2
28/05/201
2
12/10/2012
12/11/201
2
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 thal Len/dx
BM exam
no
plasma-
cytosis
PET ++
no
plasma-
cytosis
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
3

12. 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

13. 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 -- -- WMD -- NMD
% Paraprotein -- -- WQ -- --
%
UPE NMD NMD -- MD --
%Parapro.(Ur) -- -- -- 44.1 --
%
S. Free Kappa -- -- 0.64 -- 7.44 3.30-19.40
mg/L
S. Free Lambda -- -- 127H -- 523H 5.71-26.30
mg/L
S. Free K/L Ratio -- -- 0.005 -- 0.014
retrospective assay

14. 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 -- -- MD MD MD
Total protein -- -- 79.0 68.0 64.0 g/l
% Paraprotein -- -- 3.0 3.0 2.1 %
Paraprotein -- -- 2.4 2.0 1.3 g/l
UPE MD -- -- -- --
%Parapro.(Ur) 88.2 -- -- -- -- %
S. Free Kappa -- -- -- 6.86 -- 3.30-19.40 mg/L
S. Free Lambda -- -- -- 5790 -- 5.71-26.30 mg/L
S. K/L Ratio -- -- -- 0.0012 --
IgG paraprotein levels stable
UPE & SFL increasing

15. 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 -- 8 L -- 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 -- WMD -- WMD WMD
Total protein -- 54.0 -- 67.0 61.0
g/l
% Paraprotein -- 1.2 -- 2.4 2.7
%
Paraprotein -- 0.6 -- 1.6 1.6
g/l
UPE MD -- -- -- --

16. http://www.bindingsite.com/lightchainescape