International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

A. Dispenzieri, R. Kyle, G. Merlini, J.S. Miguel, H. Ludwig, R. Hajek, A. Palumbo, S. Jagannath, J. Blade, S. Lonial, M. Dimopoulos, R. Comenzo, H. Einsele, B. Barlogie, K. Anderson, M. Gertz, J.L. Harousseau, M. Attal, P. Tosi, P. SonneveldM. Boccadoro, G. Morgan, P. Richardson, O. Sezer, M.V. Mateos, M. Cavo, D. Joshua, I. Turesson, W. Chen, K. Shimizu, R. Powles, S.V. Rajkumar, B.G.M. Durie, Dina Ben-Yehuda-Salz

Research output: Contribution to journalArticlepeer-review

700 Scopus citations


The serum immunoglobulin-free light chain (FLC) assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.
Original languageEnglish
Pages (from-to)215-224
Number of pages10
Issue number2
StatePublished - 2009

Bibliographical note

Cited By :655

Export Date: 3 October 2022


Correspondence Address: Dispenzieri, A.; Division of Hematology and Laboratory Medicine, , Rochester, MN, United States

Chemicals/CAS: bortezomib, 179324-69-7, 197730-97-5; cisplatin, 15663-27-1, 26035-31-4, 96081-74-2; cyclophosphamide, 50-18-0; dexamethasone, 50-02-2; doxorubicin, 23214-92-8, 25316-40-9; etoposide, 33419-42-0, 433304-61-1; thalidomide, 50-35-1

References: Bradwell, A.R., Carr-Smith, H.D., Mead, G.P., Tang, L.X., Showell, P.J., Drayson, M.T., Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine (2001) Clin Chem, 47, pp. 673-680; Bradwell, A.R., Serum free light chain measurements move to center stage (2005) Clin Chem, 51, pp. 805-807; Bradwell, A.R., Carr-Smith, H.D., Mead, G.P., Harvey, T.C., Drayson, M.T., Serum test for assessment of patients with Bence Jones myeloma (2003) Lancet, 361, pp. 489-491; Katzmann, J.A., Clark, R.J., Abraham, R.S., Bryant, S., Lymp, J.F., Bradwell, A.R., Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: Relative sensitivity for detection of monoclonal light chains (2002) Clin Chem, 48, pp. 1437-1444; Nakano, T., Nagata, A., ELISAs for free light chains of human immunoglobulins using monoclonal antibodies: Comparison of their specificity with available polyclonal antibodies (2003) J Immunol Methods, 275, pp. 9-17; Tate, J.R., Mollee, P., Dimeski, G., Carter, A.C., Gill, D., Analytical performance of serum free light-chain assay during monitoring of patients with monoclonal light-chain diseases (2007) Clin Chim Acta, 376, pp. 30-36; Daval, S., Tridon, A., Mazeron, N., Ristori, J.M., Evrard, B., Risk of antigen excess in serum free light chain measurements (2007) Clin Chem, 53, pp. 1985-1986; Le Bricon, T., Bengoufa, D., Benlakehal, M., Bousquet, B., Erlich, D., Urinary free light chain analysis by the Freelite immunoassay: A preliminary study in multiple myeloma (2002) Clin Biochem, 35, pp. 565-567; Snozek, C.L., Katzmann, J.A., Kyle, R.A., Dispenzieri, A., Larson, D.R., Therneau, T.M., Prognostic value of the serum-free light chain ratio in patients with newly diagnosed myeloma and proposed incorporation into the International Staging System (2008) Leukemia, 22, pp. 1933-1937; Mead, G.P., Carr-Smith, H.D., Drayson, M.T., Morgan, G.J., Child, J.A., Bradwell, A.R., Serum-free light chains for monitoring multiple myeloma (2004) Br J Haematol, 126, pp. 348-354; Kang, S.Y., Suh, J.T., Lee, H.J., Yoon, H.J., Lee, W.I., Clinical usefulness of free light chain concentration as a tumor marker in multiple myeloma (2005) Ann Hematol, 84, pp. 588-593; Dispenzieri, A., Zhang, L., Katzmann, J.A., Snyder, M., Blood, E., Degoey, R., Appraisal of immunoglobulin free light chain as a marker of response (2008) Blood, 111, pp. 4908-4915; Drayson, M., Tang, L.X., Drew, R., Mead, G.P., Carr-Smith, H., Bradwell, A.R., Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma (2001) Blood, 97, pp. 2900-2902; Katzmann, J.A., Abraham, R.S., Dispenzieri, A., Lust, J.A., Kyle, R.A., Diagnostic performance of quantitative {kappa} and {lambda} free light chain assays in clinical practice (2005) Clin Chem, 51, pp. 878-881; Abraham, R.S., Clark, R.J., Bryant, S.C., Lymp, J.F., Larson, T., Kyle, R.A., Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma (2002) Clin Chem, 48, pp. 655-657; Dispenzieri, A., Kyle, R.A., Katzmann, J.A., Therneau, T.M., Larson, D., Benson, J., Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma (2008) Blood, 111, pp. 785-789; Rajkumar, S.V., Kyle, R.A., Therneau, T.M., Melton III, L.J., Bradwell, A.R., Clark, R.J., Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance (2005) Blood, 106, pp. 812-817; Abraham, R.S., Katzmann, J.A., Clark, R.J., Bradwell, A.R., Kyle, R.A., Gertz, M.A., Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis (2003) Am J Clin Pathol, 119, pp. 274-278; Lachmann, H.J., Gallimore, R., Gillmore, J.D., Carr-Smith, H.D., Bradwell, A.R., Pepys, M.B., Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy (2003) Br J Haematol, 122, pp. 78-84; Katzmann, J.A., Dispenzieri, A., Kyle, R.A., Snyder, M.R., Plevak, M.F., Larson, D.R., Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays (2006) Mayo Clin Proc, 81, pp. 1575-1578; Beetham, R., Wassell, J., Wallage, M.J., Whiteway, A.J., James, J.A., Can serum free light chains replace urine electrophoresis in the detection of monoclonal gammopathies? (2007) Ann Clin Biochem, 44, pp. 516-522; Nowrousian, M.R., Brandhorst, D., Sammet, C., Kellert, M., Daniels, R., Schuett, P., Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma (2005) Clin Cancer Res, 11, pp. 8706-8714; Hill, P.G., Forsyth, J.M., Rai, B., Mayne, S., Serum free light chains: An alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies (2006) Clin Chem, 52, pp. 1743-1748; Abadie, J.M., Bankson, D.D., Assessment of serum free light chain assays for plasma cell disorder screening in a veterans affairs population (2006) Ann Clin Lab Sci, 36, pp. 157-162; Bakshi, N.A., Gulbranson, R., Garstka, D., Bradwell, A.R., Keren, D.F., Serum free light chain (FLC) measurement can aid capillary zone electrophoresis in detecting subtle FLC-producing M proteins (2005) Am J Clin Pathol, 124, pp. 214-218; Marien, G., Oris, E., Bradwell, A.R., Blanckaert, N., Bossuyt, X., Detection of monoclonal proteins in sera by capillary zone electrophoresis and free light chain measurements (2002) Clin Chem, 48, pp. 1600-1601; Kumar, S., Fonseca, R., Dispenzieri, A., Katzmann, J.A., Kyle, R.A., Clark, R., High incidence of IgH translocations in monoclonal gammopathies with abnormal free light chain levels (2006) ASH Annual Meeting Abstracts, 108, p. 3514; Dispenzieri, A., Lacy, M.Q., Katzmann, J.A., Rajkumar, S.V., Abraham, R.S., Hayman, S.R., Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation (2006) Blood, 107, pp. 3378-3383; van Rhee, F., Bolejack, V., Hollmig, K., Pineda-Roman, M., Anaissie, E., Epstein, J., High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis (2007) Blood, 110, pp. 827-832; Kyle, R.A., Remstein, E., Therneau, T.M., Dispenzieri, A., Kurtin, P.J., Hodnefield, J., Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma (2007) New Engl J Med, 356, pp. 2582-2590; Dingli, D., Kyle, R.A., Rajkumar, S.V., Nowakowski, G.S., Larson, D.R., Bida, J.P., Immunoglobulin free light chains and solitary plasmacytoma of bone (2006) Blood, 108, pp. 1979-1983; Kyrtsonis, M.C., Vassilakopoulos, T.P., Kafasi, N., Sachanas, S., Tzenou, T., Papadogiannis, A., Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma (2007) Br J Haematol, 137, pp. 240-243; Greipp, P.R., San Miguel, J., Durie, B.G., Crowley, J.J., Barlogie, B., Blade, J., International staging system for multiple myeloma (2005) J Clin Oncol, 23, pp. 3412-3420; Palladini, G., Lavatelli, F., Russo, P., Perlini, S., Perfetti, V., Bosoni, T., Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL (2006) Blood, 107, pp. 3854-3858; Sanchorawala, V., Seldin, D.C., Magnani, B., Skinner, M., Wright, D.G., Serum free light-chain responses after high-dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis (2005) Bone Marrow Transplant, 36, pp. 597-600; Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol 2005; 79: 319-328; Durie, B.G., Harousseau, J.L., Miguel, J.S., Blade, J., Barlogie, B., Anderson, K., International uniform response criteria for multiple myeloma (2006) Leukemia, 20, pp. 1467-1473; Cohen, A.D., Zhou, P., Chou, J., Teruya-Feldstein, J., Reich, L., Hassoun, H., Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone+/-thalidomide for systemic light-chain amyloidosis: Results of a phase II trial (2007) Br J Haematol, 139, pp. 224-233; Blade, J., Samson, D., Reece, D., Apperley, J., Bjorkstrand, B., Gahrton, G., Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant (1998) Br J Haematol, 102, pp. 1115-1123; Singhal, S., Stein, R., Vickrey, E., Mehta, J., The serum-free light chain assay cannot replace 24-h urine protein estimation in patients with plasma cell dyscrasias (2007) Blood, 109, pp. 3611-3612; Hajek, R., Cermakova, Z., Pour, L., Novontna, H., Maisnar, V., Tichy, M., Free light chain assays for early detection of resistance to bortezomib-based regimens (2007) Haematologica, 92, p. 93; Hassoun, H., Reich, L., Klimek, V.M., Dhodapkar, M., Cohen, A., Kewalramani, T., Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma (2006) Br J Haematol, 132, pp. 155-161; Dawson, M.A., Patil, S., Spencer, A., Extramedullary relapse of multiple myeloma associated with a shift in secretion from intact immunoglobulin to light chains (2007) Haematologica, 92, pp. 143-144


  • bortezomib
  • cisplatin
  • cyclophosphamide
  • dexamethasone
  • doxorubicin
  • etoposide
  • immunoglobulin kappa chain
  • immunoglobulin lambda chain
  • immunoglobulin light chain
  • M protein
  • thalidomide
  • amyloidosis
  • capillary zone electrophoresis
  • diagnostic accuracy
  • diagnostic value
  • disease free survival
  • human
  • immunoassay
  • immunoglobulin blood level
  • light chain
  • light chain amyloidosis
  • lymphoproliferative disease
  • monoclonal immunoglobulinemia
  • multiple cycle treatment
  • multiple myeloma
  • overall survival
  • patient monitoring
  • peripheral blood stem cell transplantation
  • plasmacytoma
  • practice guideline
  • priority journal
  • prognosis
  • protein electrophoresis
  • protein urine level
  • review
  • screening test
  • sensitivity and specificity
  • serum free light chain assay
  • treatment response


Dive into the research topics of 'International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders'. Together they form a unique fingerprint.

Cite this