The Addition of sFLCR Improves ISS Prognostication in Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1490-1490 ◽  
Author(s):  
Marie-Christine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Nikolitsa Kafasi ◽  
Dimitris Maltezas ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Light Chain ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Prognostic Information ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Poor Outcomes ◽  
Chain Type

Abstract We have recently shown that serum free light chain ratio (sFLCR) provides independent prognostic information in patients with newly diagnosed MM (Kyrtsonis et al, Br J Haematol, 137: 240–243, 2007). The aim of the present study was to extend our previous observations in a multicenter setting and to investigate the potential additive effect of sFLCR to the ISS system, in determining the prognosis of patients with MM. We analyzed 214 newly diagnosed MM patients (125 kappa-, 89 lambda-). Serum free light chain levels were measured in sera drawn at diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK). Then, the sFLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Based on our previous study “high” sFLCR was defined as ratios ≥3.57 and ≥45.09 for kappa- and lambda- MM respectively. The median age of the patients was 68 years (33–92), 51% were males, 28%, 30%, and 42% had Durie-Salmon stages I, II, and III, 14% creatinine >2 mg/dl, and 13% had Bence-Jones MM. ISS stage was 1, 2, or 3 in 33%, 33%, and 34% of the patients, 48% had CRP ≥4 mg/l, 18% elevated LDH, 31% hemoglobin <10 g/dl, 32% albumin <3.5 g/dl, and 51% bone marrow infiltration ≥50%. The median sFLCR was 6.00 in the 125 kappa-MM, and 46.43 in the 89 lambda-MM patients. With a median follow-up of 16 months (1–105), 88 MM patients with “low” sFLCR had a 3-year disease specific survival (DSS) of 93±4% vs. 63±6% for 126 patients with “high” sFLCR. The corresponding 5-year DSS rates were 83±7% vs. 43±10% (p=0.0001). In multivariate analysis, “high” sFLCR provided prognostic information independent of the value of ISS, as further reflected by the data presented in the table. LDH levels further contributed in the discrimination of prognosis in multivariate analysis: A subgroup of 19 patients (9% of total) with “high” sFLCR plus ISS=3 plus elevated LDH had a 0% projected DSS at 19 months. sFLCR and the previously described models remained predictive of the outcome, if only patients requiring treatment at diagnosis were analyzed. In conclusion, baseline sFLCR appears to be an easily determined, powerful, independent and very promising novel prognostic factor for survival in patients with newly diagnosed MM. Establishment of the optimal cutoff and prospective validation is needed. Its addition to ISS and LDH can identify subgroups of patients with excellent or very poor outcomes. DSS According to the Combined sFLCR and ISS System Patient Subgroup Pts (#,%) 3-yr DSS (%) 5-yr DSS (%) p “Low” sFLCR and ISS <3 61 (29) 95 90 Either “High” sFLCR or ISS=3 96 (46) 82 56 <0.0001 “High” sFLCR and ISS=3 50 (24) 37 24

Serum Free Kappa to Free Lambda Ratios as an Adjunct to Serum Protein Electrophoresis for the Detection of Monoclonal Proteins in the Serum.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4856-4856
Author(s):  
Arthur R. Bradwell ◽  
Jean Garbincius ◽  
Earle W. Holmes
Keyword(s):  
Serum Protein ◽  
Light Chain ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Serum Protein Electrophoresis ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
Monoclonal Proteins

Abstract Serum free light chain measurements have been shown to be useful in the diagnosis and monitoring of patients with monoclonal gammopathies. The present study was undertaken to evaluate the effect of adding the measurement of serum free light chain kappa to lambda ratios to the serum protein electrophoresis evaluation that we typically use as an initial screen for the detection of monoclonal proteins. We retrospectively tested 347 consecutive samples from individuals who had no previous history of plasma cell dyscrasia and had not previously had a serum or urine electrophoresis or immunofixation electrophoresis test at our institution. The quantitative serum protein electrophoresis test that was ordered was performed using Hydragel Beta 1- Beta 2 gels and Hydrasis instrument (Sebia, Inc., Norcross, GA). The protein content of the electrophoresis zones were quantitated by scanning densitometry and the electrophoresis pattern of each sample was qualitatively examined for abnormal bands and suspicious findings by a single, experienced observer. Serum free light chain concentrations and the serum free light chain kappa to lambda ratios were determined using the Freelite Human Kappa and Lambda Kits (The Binding Site Ltd, Birmingham, UK) and the Immage analyzer (Beckman Coulter Inc., Brea, CA). The serum free light chain kappa to lambda ratios were outside the reference interval (0.25 to1.65) in 23 of the samples. Ten abnormal ratios were observed among a group of 57 samples that had either positive or suspicious qualitative evaluations for the presence of a restriction or that demonstrated hypo-gammaglobulinemia. Both abnormalities led to recommendations for follow-up testing, which confirmed the presence of a monoclonal protein in 21 of the samples. Six abnormal ratios were observed among a group of 159 specimens that had quantitative abnormalities in albumin or one or more of globulin fractions (hypo-gammaglobulinemia excepted) and normal qualitative evaluations. Seven abnormal ratios were observed among a group of 131 samples that had normal quantitative results and normal qualitative evaluations. Follow-up testing is not usually recommended for serum protein electrophoresis results like those in the latter two groups. We found that the addition of the serum free light chain kappa to lambda ratio to the serum protein electrophoresis test increased the number of abnormal screens that would have required further clinical and/or laboratory evaluation by 23%(i.e. from 57 to 70). Given the high specificity of the serum free light chain kappa to lambda ratio for monoclonal light chains, the additional 13 abnormal samples identified by this test are expected to have a high likelihood of harboring a monoclonal protein that would have otherwise eluded detection. Pending a definitive prospective study, we estimate that the addition of a serum free light chain kappa to lambda ratio to the serum protein electrophoresis screen would increase the rate of detection of serum monoclonal proteins by as much as 1.6-fold.

Serum Free Light Chain Assessment in 311 Patients with Gammopathy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4750-4750
Author(s):  
Fernanda Trigo ◽  
Cristina Guimaraes ◽  
Abilia Bodas ◽  
Armando Teixeira-Pinto ◽  
Jose E. Guimaraes
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity And Specificity ◽  
Light Chain ◽  
Final Diagnosis ◽  
Reference Intervals ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Total Light

Abstract Serum free light chain (FLC) levels are a useful multiple myeloma (MM) marker and a indicator of tumour burden both for diagnosis and follow up purposes. A total of 311 patient samples were assayed in our laboratory for FLC and the kappa/lambda (κ/λ) chain ratio was calculated and compared with the classical methods for characterization of gammopathy (immunofixation, IMF, immunoglobulin levels and total light chain levels and respective ratio). Ig (A, G, M) and total κ and λ chain levels were assayed by nephlometry (Dade-Behring BNII). Immunofixation was performed in a Hydrasys (Sebia) setting. FLC assay was done using Binding Site reagents (Dade-Behring). Statistical analysis was performed by SPSS® for Windows v. 15. Concordance between IMF results and free κ/λ chain ratio was calculated. Sensitivity and specificity of the free κ/λ chain ratio in the identification of positive and negative IMF were also determined. Reference intervals used for free κ/λ and total κ/λ chain ratios were [0.26; 1.65] and [1.35; 2.65], respectively. Out of 311 patients with gammopathy studied, 235 had absence of monoclonality as defined by the immunoelectrophoretic profile. Inclusively, only 51% of the 53 patients with suspected MM and 66% of the 41 patients with a diagnosis of MGUS were IMF positive. Sensitivity and specificity of total κ/λ chain ratio for identification of positive or negative IMF were respectively 70% and 91% with a global concordance of 86%. In 215 (70%) patients, IMF and free κ/λ chain ratio were in agreement. However, 74 (32%) of IMF negative patients had abnormal free κ/λ chain ratio: 18% had a final diagnosis of chronic renal failure, 13% of CLL or NHL, 9% of MGUS, 7% of MM and 3% of amyloidosis; the remainder 50% were diagnosed as having a disease other than lymphoplasmacytic disorder. These results stress the value of free light chain determination in the diagnosis and follow up of gammopathies and its usefulness as a marker for multiple myeloma and associated monoclonal gammopathies.

Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2900-2902 ◽  
Author(s):  
Mark Drayson ◽  
Lian X. Tang ◽  
Roger Drew ◽  
Graham P. Mead ◽  
Hugh Carr-Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Activity ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Using sensitive, automated immunoassays, increased concentrations of either κ or λ free light chains (and abnormal κ/λ ratios) were detected in the sera of 19 of 28 patients with nonsecretory multiple myeloma. Four other patients had suppression of one or both light chains, and the remaining 5 sera had normal or raised free light-chain concentrations with substantially normal κ/λ ratios. Six of the patients with an elevated single free light chain, who were studied during follow-up, had changes in disease activity that were reflected by the changes in free light-chain concentrations. It is concluded that quantification of free light chains in serum should prove useful for the diagnosis and monitoring of many patients with nonsecretory myeloma.

Elevated, combined serum free light chain levels and increased mortality: a 5-year follow-up, UK study

2012 ◽  
Vol 65 (11) ◽  
pp. 1036-1042 ◽  
Author(s):  
Seetharam Anandram ◽  
Lakhvir Kaur Assi ◽  
Tracy Lovatt ◽  
Jayne Parkes ◽  
Joanne Taylor ◽  
...  
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Kaplan Meier ◽  
Risk Of Mortality ◽  
Patients At Risk ◽  
Risk Patients ◽  
Almost All

AimsAbnormal serum free light chain (FLC) ratios are diagnostically important in almost all plasma cell disorders. However, absolute increases in polyclonal FLC levels are often discarded as inconsequential. Here we report an association between increased combined polyclonal FLC (cFLC: FLCκ plus FLCλ) concentrations and mortality.Methods723 patients sent for 30 routine haematological assessments were enrolled. Patients with a confirmed monoclonal gammopathy were removed. The remaining 527 patients were followed up for up to 4.5 years. Statistical analysis was performed using SPSS (V.19).ResultsDuring follow-up, there were 99 deaths (18.8%). Kaplan-Meier survival analysis revealed 29% of these deaths occurred within the first 100 days (N=29). Multivariate analysis identified only cFLC >65 mg/l, albumin <33 g/l and  estimated glomerular filtration rate <30 ml/min/1.73 m2 to be independently associated with mortality within 100 days and 4.5 years with, cFLC having the highest HR of 7.1. A simple risk stratification model based only on albumin and cFLC identified 86% mortality within 100 days and 62% over 4.5 years.ConclusionsElevated cFLC is significantly associated with increased mortality and with albumin can be used to identify patients at risk of mortality at 4.5 years with high-risk patients detected within 100 days.

Serum Free Light Chain [FLC] Assay in Multiple Myeloma Patients Who Achieved Negative Immunofixation after Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2023-2023 ◽  
Author(s):  
Ulrike Moesbauer ◽  
Heike Schieder ◽  
Helmut Renges ◽  
Francis Ayuk ◽  
Axel Zander ◽  
...  
Keyword(s):  
Complete Remission ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Group 3 ◽  
Light Concentration ◽  
Group 2 ◽  
Group 1

Abstract The quantitative assay for free light chains [FLC] has been reported to be sensitive and specific for detecting and monitoring free light chain diseases such as multiple myeloma. To evaluate the sensitivity of FLC for monitoring patients in complete remission for early detection of relapse, the measurement of more than 250 serum free light chains were performed with the commercial available Freelite TM kit [Binding Site] in 26 patients who achieved complete remission with negative immunofixation after dose reduced allogeneic stem cell transplantation. The patient groups were divided in those who remained immunofixation negative [n=12, group 1] during follow-up of at least 1 year and those who had been immunofixation negative but became positive during follow-up [n=9, group 2] and those who had achieved near complete remission with positive immunofixation but then became immunofixation negative during follow-up [n=5, group 3]. In group 1 the measuring of 105 FLC concentration and kappa/lambda ratio was performed in 12 patients. In 10 patients [83 %] free light concentration of kappa or lambda remained within the normal range during follow-up of more than 1 year. In 2 patients [17 %] kappa or lambda FLC concentration was above the normal range, but remained stable without any signs of increasing amount. Group 2 consisted of 9 patients who had been immunofixation negative but became positive during follow-up. In all patients an increase of the corresponding free light chain could be observed in serum. In 4 patients a very close monitoring of immunofixation and free light assay was performed and an at least 25 % increase of the free light concentration in serum was observed at a median of 97 days before immunfixation became positive. In group 3 five patients who had been immunofixation positive became negative during follow-up. In all of the patients the free light concentration was within the range at time of negative immunofixation. The corresponding free light concentration dropped down and reached normal level at a median of 38 days before the patients had achieved negativity of immunofixation. These results suggest that serum free light chain assay allows monitoring of patients with complete remission and might detect early relapse before immunofixation becomes positive. Thus, an early increase of free light chain assay in immunofixation negative patients after allogeneic transplantation might be an useful guide for adoptive immunotherapy strategies to prevent clinical relapse.

Normalization of the Serum Free Light Chain (FLC) Ratio Is Associated with Superior Overall Survival among Myeloma Patients Achieving Immunofixation Negative State: Results Support Incorporation of Serum FLC Ratio in Stringent CR Definition.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1692-1692 ◽  
Author(s):  
Shaji Kumar ◽  
Angela Dispenzieri ◽  
Dirk Larson ◽  
Colin Colby ◽  
Robert Kyle ◽  
...  
Keyword(s):  
Overall Survival ◽  
Light Chain ◽  
Median Overall Survival ◽  
Free Light Chain ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Protein Levels ◽  
Serum Free Light Chain ◽  
Serum And Urine

Abstract Background: Traditionally response to therapy in multiple myeloma (MM) is based on changes in the serum and urine monoclonal protein by immunoelectrophoresis. Immunofixation allows for detection of small amounts of monoclonal protein that cannot be quantitated on immunoelectrophoresis. Serum immunoglobulin free light chain (FLC) assay allows for detection of unbound kappa and lambda free light chain and has allowed disease measurement in patients with oligosecretory myelomas and can potentially allow detection of low levels of tumor burden, below the threshold of the standard tests. We examined this hypothesis in patients who had obtained a negative immunofixation in serum and urine following treatment of their MM. Methods: For the purposes of the study, we included selected patients with MM who had measurable monoclonal (M) protein levels at baseline (defined as &gt;1 gm/dL in the serum or &gt;200 mg/24 hour in the urine or involved free light chain &gt; 10 mg/dL) on protein electrophoresis; patients with non-secretory and oligo-secretory myeloma were excluded. We then identified patients who since 1995 had a negative immunofixation in the serum and urine, all done at the same time (within 30 days of each other). Baseline demographics and clinical characteristics; date of diagnosis, last follow up, and follow up status; serum and urine M protein levels at diagnosis; and results of serum and urine immunofixation, and serum free light chain (FLC) ratio within 30 days of the immunofixation were all collected from the existing databases. Results: Eighty-four patients met the criteria for the study, all of whom had measurable disease at baseline and subsequently achieved negative immunofixation in serum and urine. Among these, 46 patients (55%) also had a normal FLC ratio (K/L ratio; 0.26–1.65). Th median time from diagnosis to the documented immunofixation was 7.5 months (range, 1–157). The median overall survival from diagnosis among those with a normal FLC ratio along with negative immunofixation was not reached compared to 76 months for those with abnormal FLC ratio, P = 0.02. The median overall survival from the documentation of negative immunofixation was not reached for the group with normal FLC ratio compared to 46.5 months for those with an abnormal FLC, P = 0.03. Conclusion: Attainment of a normal FLC ratio at the time of serum and urine immunofixation negative status identifies a group of patients with better outcome. The presence of an abnormal FLC ratio likely represents persistence of the clonal population that is secreting none or very small amounts of monoclonal protein. The data presented here supports the inclusion of FLC measurements as part of response criteria for MM as has been done for the definition of stringent CR in the IMWG response criteria. Figure: Overall survival from diagnosis in patients with or with out a normal FLC ratio at the time of serum and urine immunofixation. Figure:. Overall survival from diagnosis in patients with or with out a normal FLC ratio at the time of serum and urine immunofixation.

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