Freelite®
and Hevylite®
Key Terminology Freelite
Term Definition
uFLC Ratio iFLC
dFLC
Uninvolved free light chains (polyclonal FLC production)
sFLC (measures clonality)
Involved free light chains (monoclonal FLC production)
Difference calculation (iFLC – uFLC) indicates response to treatment
Hevylite Term
iHLC uHLC HLC Ratio dHLC
HLC pair suppression
Example in a LCMM patient
References
1. Dispenzieri A, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23:215–224
2. Fischer C, et al. Kappa free light chains in cerebrospinal fluid as markers of intrathecal immunoglobulin synthesis. Clin Chem 2004;50:1809-1813.
3. Kyle RA, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010: 24:1121-1127
4. Dimopoulos M, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 2011 May 5;117:4701-4705
5. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncology 2014; 15:e538-e548
6. Hutchison CA, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol 2011 Nov 1;8:43-51
7. Anderson KC, et al. NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma. J Natl Compr Canc Netw 2015;13: 1398-1435
8. Myeloma: Diagnosis and management. NICE Guidelines 2016
9. Harousseau JL, et al. Multiple myeloma: ESMO Clinical Recommendations for diagnosis, treatment and followup. Ann Oncol 2009 May;20 Suppl 4: 97-99
10. Bird J, et al. British Committee for Standards in Haematology guidelines for the diagnosis and management of multiple myeloma 2014.
www.bcshguidelines.com
11. Wechalekar AD, et al. Guidelines on the management of AL amyloidosis. Br J Haematol 2015;168: 186-206 12. Gillmore JD, et al. Guidelines on the diagnosis and investigation of AL amyloidosis. Br J Haematol 2015;168: 207-218
13. Bird J, et al. UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 2009 Oct; 147:22-42
Definition
Involved heavy + light chain isotype (measures monoclonal production)
Uninvolved heavy + light chain isotype (measures polyclonal production)
Indicates clonality (& immune suppression if iHLC normal & uHLC is low)
(iHLC – uHLC)
Abormally low concentration of uHLC (and ratio abnormal)
Freelite
FLC FLC
FLC ratio
Reference Ranges Normal adult serum
Example in an IgG patient
IgG IgG IgG/IgG IgG-IgG Low IgG
14. Comenzo RL, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain (AL) amyloidosis. Leukemia 2012;26: 2317-2325
15. Zhonghua Nei Ke Za Zhi. The guidelines for the diagnosis and management of multiple myeloma in China (2015 revision) : interpretation of initial treatment. 2016 Feb;55(2):92-3. doi: 10.3760/
cma.j.issn.0578-1426.2016.02.003
16. Tietsche de Moraes Hungria Vania, et al. Guidelines on the diagnosis and management of multiple myeloma treatment: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Project guidelines: Associação Médica Brasileira. Rev Bras Hematol Hemoter 2013;35:201-17
17. Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncology 2016;17:e328-346
18. Multiple myeloma diagnosis and treatment. Transfuze a Hematologie Dnes, suppl. 1, 18, 2012
19. Dmoszynska A, et al. Guidelines of Polish Myeloma Group concerning diagnosis and therapy of multiple myeloma and other plasmacytic dyscrasias for 2013. Acta Haem Polo 2013;44: 3-47
20. Katzmann JA, et al. Serum Reference Intervals and Diagnostic Ranges for Free and Free Immunoglobulin Light Chains: Relative Sensitivity for Detection of Monoclonal Light Chains. Clin Chem 2002; 48:1437-1444
21. Hutchison CA, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrology 2008; 9:11
22. Katzmann JA, et al. Screening Panels for Detection of Monoclonal Gammopathies. Clin Chem 2009; 55:1517-1522
23. Hill PG, et al. Serum Free Light Chains: An Alternative to the Urine Bence Jones Proteins Screening Test for Monoclonal Gammopathies. Clin Chem 2006; 52:1743-1748
24. Katzmann JA, et al. Elimination of the Need for Urine Studies in the Screening Algorithm for Monoclonal Gammopathies by Using Serum Immunofixation and Free Light Chain Assays. Mayo Clin Proc 2006; 81:1575-1578
25. Bradwell AR, et al. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003; 361:489-491
26. Wolff, et al. Assessment of the analytical performance and the sensitivity of serum free light chains immunoassay in patients with monoclonal gammopathy. Clin Bio 2007; 40:351-354
27. Abraham RS, et al. Correlation of Serum Immunoglobulin Free Light Chain Quantification with Urinary Bence Jones Protein in Light Chain Myeloma. Clin Chem 2002; 48:655657
28. Drayson M, et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97:2900-2902
29. van Rhee F, et al. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 2007; 110:827-832
95 percentile range 3.30 - 19.40 (mg/L)
5.71 - 26.30 (mg/L)
100 percentile range 0.26 - 1.65
30. Snozek CLH, et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008; 22:1933-1937
31. Kyrtsonis M, et al. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. Br J Haematol 2007; 137:240- 243
32. Kyrtsonis M, et al. The Addition of sFLCR Improves ISS Prognostication in Multiple Myeloma (MM). Blood 2007;110:1490a
33. Rajkumar S, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106:812-817
34. Mateos A, et al. Smoldering Multiple Myeloma: When to Observe and When to Treat? Asco Educational Book 2015; e484-e492
35. Dispenzieri A, et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006;107:3378-3383
36. Kumar V, et al. Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements. JCO 2012;30(9):989-95
37. Katzmann J, et al. Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS. Leukemia 2013;27: 208-212
Hevylite Normal adult serum
IgG Kappa IgG Lambda IgG/IgG Ratio
IgA Kappa IgA Lambda IgA/IgA Ratio
IgM Kappa IgM Lambda IgM/IgM Ratio
95 percentile range for SPAPLUS®
3.84 - 12.07 (g/L) 1.91 - 6.74 (g/L) 1.12 - 3.21
0.57 - 2.08 (g/L) 0.44 - 2.04 (g/L) 0.78 - 1.94
0.19 - 1.63 (g/L) 0.12 - 1.01 (g/L) 1.18 - 2.74
38. Mead GP, et al. Serum free light chains for monitoring multiple myeloma. Br J Haematol 2004; 126:348-354 39. Tate et al. Serum free light chains for monitoring multiple myeloma. Br J Haematol 2005; 128:405-406
40. Mösbauer et al. Monitoring serum free light chains in patients with multiple myeloma who achieved negative immunofixation after allogeneic stem cell transplantation. Haematologica 2007; 92:275-276
41. Mead et al. Response to: Serum free light chains for monitoring multiple myeloma. Br J Haematol 2005;128:406-407
42. Dawson et al. Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains. Haematologica 2007; 92:143-144
43. Kühnemund A, et al. ‘Light chain escape-multiple myeloma’ - an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring. J Cancer Res Clin Oncol 2009; 135:477-484
44. Boyle E, et al. IgA Kappa/IgA Lambda Heavy/Light Chain Assessment in the Management of Patients with IgA Myeloma. Cancer 2014;120:3952-3957
45. Elssner-Freund, J et al. IgA subtypes: A supplement to M-protein quantification by electrophoretic methods in monitoring patients with multiple myeloma. Hematology Reports 2015; 7:47:F102
46. Ludwig H, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients. Leukemia 2013,27:213-2195
47. Amolak, Bansalet al. Assessment of IgA Heavy/Light Chain immunoassays utility in Multiple Myeloma patients. Biochimica Clinica 2013; 37(SS):S610
48. Bengoufa D, et al. Usefulness of a Hevylite immunoassay in serum for the diagnosis and the follow-up of IgA monoclonal gammopathy. Hematology Reports 2010; 2(1s):58:G68
49. Steele P, et al. Evaluation of Novel Nephelometric Assays for the Quantification of Serum Immunoglobulins in Monoclonal Gammopathies. Hematology Reports 2010; 2(1s):53-54:F60]
50. Katzmann J, et al. Monitoring IgA Multiple Myeloma: Immunoglobulin Heavy/Light Chain Assays. Clin Chem 2015;61:360-367 51. Lakomy D, et al. valuation of the new HevyliteTM
Hem and Onc 2012;1:9 IgA assay for the diagnosis and follow-up of monoclonal gammopathies. Exp More information at:
www.bindingsite.com 15
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