Appraisal of immunoglobulin free light chain as a marker of response.

The immunoglobulin free light chain (FLC) assay is an invaluable tool for following patients with oligosecretory plasma cell dyscrasia. Baseline values have also been shown to be prognostic in all plasma cell disorders tested. A looming question, however, is the role it should play in following myeloma patients with disease that is measurable using serum and urine electrophoresis. We used the data and stored samples from a mature Eastern Cooperative Oncology Group clinical trial (E9486) to assess serum levels of FLC at baseline and after 2 months of alkylator-based therapy. For serial determinations, the absolute level of involved serum FLC or the difference of the involved and uninvolved FLC is preferred over the ratio of involved to uninvolved FLC. FLC response after 2 months of therapy was superior to early M-protein measurement to predict overall response. The ideal cut-point for FLC change appears to be between 40% and 50% reduction. The correlation between serial measurements of serum FLC and urine M-protein is inadequate to abolish the serial 24-hour urine protein. Although baseline values of FLC are prognostic in newly diagnosed myeloma patients, serial measurements do not appear to have added value in patients who have M-proteins measurable by electrophoresis.

[1]  B. Barlogie,et al.  Response: Top tertile SFLC reduction indeed is an independent feature of myeloma aggressiveness , 2008 .

[2]  A. Dispenzieri Is early, deep free light chain response really an adverse prognostic factor? , 2008, Blood.

[3]  T. Therneau,et al.  Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. , 2008, Blood.

[4]  B. Barlogie,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. , 2007, Blood.

[5]  M. Angelopoulou,et al.  Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma , 2007, British journal of haematology.

[6]  S. Singhal,et al.  The serum-free light chain assay cannot replace 24-hour urine protein estimation in patients with plasma cell dyscrasias. , 2007, Blood.

[7]  D. Willems,et al.  Assessment of the analytical performance and the sensitivity of serum free light chains immunoassay in patients with monoclonal gammopathy. , 2007, Clinical biochemistry.

[8]  G. Dimeski,et al.  Analytical performance of serum free light-chain assay during monitoring of patients with monoclonal light-chain diseases. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[9]  M. Drayson,et al.  Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. , 2006, Blood.

[10]  T. Therneau,et al.  Immunoglobulin free light chains and solitary plasmacytoma of bone. , 2006, Blood.

[11]  S. Ansell,et al.  Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. , 2006, Blood.

[12]  S. Seeber,et al.  Serum Free Light Chain Analysis and Urine Immunofixation Electrophoresis in Patients with Multiple Myeloma , 2005, Clinical Cancer Research.

[13]  T. Therneau,et al.  Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. , 2005, Blood.

[14]  R. Falk,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 , 2005, American journal of hematology.

[15]  A. Dispenzieri,et al.  Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. , 2005, Clinical chemistry.

[16]  J. Tate,et al.  Serum free light chains for monitoring multiple myeloma , 2005, British journal of haematology.

[17]  T. Therneau,et al.  Presence of monoclonal free light chains in the serum predicts risk of progression in monoclonal gammopathy of undetermined significance , 2004, British journal of haematology.

[18]  J. Crowley,et al.  Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  M. Alyanakian,et al.  Free immunoglobulin light‐chain serum levels in the follow‐up of patients with monoclonal gammopathies: Correlation with 24‐hr urinary light‐chain excretion , 2004, American journal of hematology.

[20]  M. Pepys,et al.  Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy , 2003, British journal of haematology.

[21]  M. Drayson,et al.  Serum test for assessment of patients with Bence Jones myeloma , 2003, The Lancet.

[22]  J. Katzmann,et al.  Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. , 2003, American journal of clinical pathology.

[23]  J. Katzmann,et al.  Serum Reference Intervals and Diagnostic Ranges for Free κ and Free λ Immunoglobulin Light Chains: Relative Sensitivity for Detection of Monoclonal Light Chains , 2002 .

[24]  T. Larson,et al.  Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma. , 2002, Clinical chemistry.

[25]  M. Drayson,et al.  Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. , 2001, Blood.

[26]  M. Oken,et al.  The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma , 1999, Cancer.

[27]  S. Jagannath,et al.  CRITERIA FOR EVALUATING DISEASE RESPONSE AND PROGRESSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED BY HIGH‐DOSE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION , 1998, British journal of haematology.

[28]  D. Bloch,et al.  Comparing two diagnostic tests against the same "gold standard" in the same sample. , 1997, Biometrics.

[29]  P. Mclaughlin,et al.  Myeloma protein kinetics following chemotherapy. , 1982, Blood.

[30]  M. Mayo,et al.  Serum free light chains in the diagnosis and monitoring of patients with plasma cell dyscrasias. , 2007, Contributions to nephrology.

[31]  P. Loehrer,et al.  International Staging System for Multiple Myeloma , 2006 .

[32]  M. Beksac,et al.  International uniform response criteria for multiple myeloma , 2006, Leukemia.

[33]  A. Dispenzieri,et al.  Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. , 2005, Clinical chemistry.

[34]  It Istituto Superiore di Sanit,et al.  Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from th 10th International Symposium on Amyloid an Amyloidosis, Tours, France, 18-22 April 2004 , 2005 .

[35]  J. Katzmann,et al.  Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. , 2002, Clinical chemistry.