Serum Free Light Chain Measurement in Myeloma Patient Samples with Oligoclonal Protein Bands.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5044-5044
Author(s):  
Regina Stein ◽  
Jayesh Mehta ◽  
Eric Vickrey ◽  
William Resseguie ◽  
Seema Singhal
Keyword(s):  
Disease Activity ◽  
Serum Protein ◽  
Light Chain ◽  
Prognostic Significance ◽  
Inactive Disease ◽  
Oligoclonal Bands ◽  
Current Therapy ◽  
Light Chains ◽  
Serum Free ◽  
Monoclonal Protein

Abstract During or after therapy, patients with myeloma sometimes develop multiple protein bands that are detectable on urine/serum protein immunofixation. These so-called “oligoclonal bands” may or may not include the original monoclonal protein isotype. The phenomenon is thought to represent immune recovery with no adverse prognostic significance. Estimation of serum free light chains (SFLC) is useful in selected patients with non-secretory myeloma, and in light chain disease with anuric renal failure. The normal serum free κ:λ ratio (SFKLR) is 0.26–1.65. There are no data on SFLC levels and SFKLR in patients with oligoclonal bands. We analyzed 52 samples in 23 patients (1–6 samples per patient; median 1) with >1 monoclonal heavy and/or light chain bands on combined serum and urine immunofixation, and corresponding SFLC results. 6 samples were from 2 patients (1 and 5 samples each) known to have biclonal disease where each clone had a different light chain specificity. The remaining samples were from patients known to have a single monoclonal protein. Immunofixation on 10 (19%) samples did not show the original monoclonal protein isotype, and 42 (81%) did. 17 (33%) samples came from patients in complete remission (CR) or near-CR based on stringent conventional criteria. Based on a review of clinical and treatment history, 23 (42%) samples were classified as being from patients who had “active disease” (stable or progressive) and 29 were classified as being from patients with “inactive disease” (CR/near-CR or showing ongoing response to current therapy). SFKLR was normal in 20 (39%) samples. The table shows the relationship between SFKLR and the presence of the original paraprotein isotype, CR/near-CR, or disease activity. Subgroup Abnormal SFKLR Normal SFKLR P Original monoclonal protein 0.068 - Present 19/42 (45%) 23/42 (55%) - Absent 1/10 (10%) 9/10 (90%) Disease status 0.038 - CR/near-CR 3/17 (18%) 14/17 (82%) - Not in CR/near-CR 17/35 (49%) 18/35 (51%) Disease activity 0.10 - Inactive 14/29 (48%) 15/29 (52%) - Active 6/23 (26%) 17/23 (74%) Absence of the original monoclonal protein and CR/near-CR were significantly more likely to be associated with normal SFKLR. On the other hand, there was no significant relationship between SFKLR and disease activity. The level of monoclonal protein on serum protein electrophoresis did not correlate with SFKLR: 9 of 22 samples with monoclonal protein ≥0.2 g/dL had abnormal SFKLR compared with 11 of 30 samples with monoclonal protein <0.2 g/dL (P=0.76). Of the 6 samples from patients with known biclonal disease, 3 had normal SFKLR (1 from 1 patient and 2 from the second patient) and 3 had abnormal SFKLR (all 3 from the second patient). On the single occasion when the disease was felt to be inactive, the SFKLR was abnormal, whereas it was normal on 3 of the 5 occasions when the disease was felt to be active. This suggests that SFLC is of limited value in the uncommon situation where biclonal disease is present with both κ and λ light chains. We conclude that in myeloma patients showing multiple monoclonal bands on immunofixation on or after therapy, the presence of a normal SFKLR suggests a significantly greater likelihood of CR/near-CR.

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.

Significance of Serum Free Light Chain Estimation with Detectable Serum Monoclonal Protein on Immunofixation Electrophoresis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5048-5048
Author(s):  
Jayesh Mehta ◽  
Regina Stein ◽  
Eric Vickrey ◽  
William Resseguie ◽  
Seema Singhal
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Oligoclonal Bands ◽  
Serum Samples ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
Small Series ◽  
Immunofixation Electrophoresis

Abstract The serum free light chain (SFLC) assay is useful in detecting monoclonal protein when there no detectable M protein on immunofixation electrophoresis (IFE). There are limited data on its value when IFE is positive. In a small series of 5 patients achieving CR, normalization of SFKLR was found to precede IFE negativity by a few weeks (Moesbauer et al. ASH 2005). Results on 231 serum samples from myeloma patients (most on therapy) where serum IFE showed IgA κ (n=33), IgA λ (n=13), IgG κ (n=153), or IgG λ (n=32), and where simultaneous SFLC and immunoglobulin (Ig) estimation had been performed were analyzed. Samples with >1 monoclonal band or multiple oligoclonal bands were excluded. The serum free κ:λ ratio (SFKLR; normal 0.26–1.65) was abnormal in 113 (49%) and normal in 118 (51%). IgG and IgA levels were compared in the context of normal versus abnormal SFKLR within each of the 4 isotypes (IgA κ, IgAλ, IgG κ, IgG λ). The table below shows that involved Ig levels were higher with abnormal than with normal SFKLR. However, uninvolved Ig levels were higher with normal than with abnormal SFKLR suggesting that normalization of SFKLR may mark a response to therapy - improved uninvolved Ig levels being evidence of response. Monoclonal protein Immunoglobulin Abnormal SFKLR Normal SFKLR P IgA kappa IgA 1640 (190–4000) 515 (102–2230) 0.048 IgA kappa IgG 419 (118–1120) 404 (197–1740) 0.39 IgA lambda IgA 408 (159–696) 704 (180–779) 0.17 IgA lambda IgG 619 (495–1510) 1530 (533–1700) 0.025 IgG kappa IgA 42 (7–225) 94 (7–642) 0.0009 IgG kappa IgG 1490 (585–5560) 1260 (327–2690) 0.004 IgG lambda IgA 32 (7–121) 96 (19–562) 0.047 IgG lambda IgG 2060 (555–12300) 1050 (432–2830) 0.018 However, does normalization of SFKLR universally herald IFE negativity? This is an important unanswered question because SFKLR is normal in a high proportion of samples which still show monoclonal protein on IFE. The figures below show scatter plots of IgG and IgA for each of the 4 isotypes for normal vs abnormal SFKLR. Within each plot, there is no obvious pattern distinguishing normal (x) from abnormal (o) SFKLR. However, there are a number of normal SFKLR points with high involved and low uninvolved Ig levels where a normal SFKLR is difficult to explain. Figure Figure Figure Figure We conclude that the SFLC assay often reveals normal SFKLR even when there is a detectable monoclonal protein in the serum. Whether this always predicts eventual paraprotein clearance and achievement of IFE negativity in patients on therapy is unknown, and needs to be studied prospectively.

The Serum Free Light Chain Assay Cannot Replace 24-Hour Urine Protein Estimation in Plasma Cell Dyscrasias.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3516-3516
Author(s):  
Seema Singhal ◽  
Regina Stein ◽  
Eric Vickrey ◽  
William Resseguie ◽  
Jayesh Mehta
Keyword(s):  
Serum Creatinine ◽  
Renal Dysfunction ◽  
Light Chain ◽  
Light Chains ◽  
Urine Specimen ◽  
Urine Protein ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Protein Estimation ◽  
The Relationship

Abstract The 2005 myeloma diagnosis and management guidelines from the British Committee for Standards in Haematology (Br J Haematol2006;132:410–451) state that “Quantification of serum-free immunoglobulin light chain levels (FLC assay) and κ/λ ratio can be used as an alternative to quantifying urinary light chains." This statement is open to the interpretation that 24-hour urine collection can be given up in patients with myeloma in favor of estimating serum free light chains (SFLC). The extent of proteinuria is a powerful predictor of the development of renal dysfunction in the short- as well as long-term. There is correlation between the degree of proteinuria and the rate of progression of renal failure. Thus, proteinuria is an independent mediator of progressive renal dysfunction and not just evidence of glomerular dysfunction. Proteinuria in myeloma patients consists of not only light chains, but also of albumin and other normal proteins - and the SFLC assay provides no information on non-light chain protein excretion. We studied 174 24-hour urine specimen results from myeloma patients where there was detectable proteinuria and where simultaneous SFLC assay was performed to analyze the relationship between the extent of proteinuria and the serum free kappa:lambda ratio (SFKLR; normal 0.26–1.65). As the table below shows, a substantial proportion of myeloma patients with proteinuria have normal SFKLR ratios. Next we analyzed 40 urine samples where monoclonal protein had been quantified. The table below shows the relationship between detectable monoclonal protein in the urine and SFKLR. The SFLC assay is abnormal in most - but not all - situations where there is quantifiable monoclonal protein being excreted in the urine. Here, the sensitivity of the test is 82.5%. Next, we analyzed the relationship between serum creatinine levels, extent of total proteinuria and SFKLR in the 173 of the 174 samples (1 urine sample did not have a concomitant creatinine value). As the table below shows, there is no significant relationship between SFKLR and serum creatinine (P=0.93), but a very strong one between the extent of proteinuria and serum creatinine (P<0.0001). Our data show that (1) normal SFKLR cannot rule out significant total proteinuria, (2) SFKLR is not 100% sensitive in detecting monoclonal proteinuria, and (3) the extent of proteinuria but not SFKLR correlates with renal function. We suggest that the SFLC assay cannot replace 24-hour urine protein estimation from a clinical standpoint. Any recommendation to the contrary runs the risk of suboptimal patient monitoring. Amount of proteinuria n Abnormal SFKLR Normal SFKLR <200 mg total 105 36 (34%) 69 (66%) 200-499 mg total 31 20 (65%) 11 (35%) ≥500 mg total 38 22 (58%) 16 (42%) Total (total ptotein) 174 78 (45%) 96 (55%) <200 mg monoclonal 20 14 (70%) 6 (30%) 200-499 mg monoclonal 8 7 (88%) 1 (13%) ≥500 mg monoclonal 12 12 (100%) 0 (0%) Total (monoclonal protein) 40 33 (83%) 7 (18%) Serum creatinine (mg/dL) Total ≤1.0 1.1–2.0 2.1–4.0 >4.0 n Abnormal SFKLR 32 (41%) 38 (49%) 3 (4%) 5 (6%) 78 Normal SFKLR 35 (37%) 50 (53%) 3 (3%) 7 (7%) 95 <200 mg total proteinuria 48 (46%) 54 (52%) 1 (1%) 1 (1%) 104 200–499 mg total proteinuria 11 (35%) 18 (58%) 1 (3%) 1 (3%) 31 >500 mg total proteinuria 8 (21%) 16 (42%) 4 (11%) 10 (26%) 38

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.

scholarly journals Serum free light chain assay reduces the need for serum and urine immunofixation electrophoresis in the evaluation of monoclonal gammopathy

2009 ◽  
Vol 46 (5) ◽  
pp. 407-412 ◽  
Author(s):  
Richard B Fulton ◽  
Suran L Fernando
Keyword(s):  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Free Light Chain ◽  
Light Chains ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
Immunofixation Electrophoresis ◽  
Monoclonal Proteins ◽  
Testing Algorithm

Background The potential for serum free light chain (sFLC) assay measurements to replace urine electrophoresis (uEPG) and to also diminish the need for serum immunofixation (sIFE) in the screening for monoclonal gammopathy was assessed. A testing algorithm for monoclonal protein was developed based on our data and cost analysis. Methods Data from 890 consecutive sFLC requests were retrospectively analysed. These included 549 samples for serum electrophoresis (sEPG), 447 for sIFE, and 318 for uEPG and urine immunofixation (uIFE). A total of 219 samples had sFLC, sEPG, sIFE and uEPG + uIFE performed. The ability of different test combinations to detect the presence of monoclonal proteins was compared. Results The sFLC κ/ λ ratio (FLC ratio) indicated monoclonal light chains in 12% more samples than uEPG + uIFE. The combination of sEPG and FLC ratio detected monoclonal proteins in 49% more samples than the combination of sEPG and sIFE. Furthermore, the sEPG + FLC ratio combination detected monoclonal protein in 6% more samples than were detected by the combined performance of sEPG, sIFE, uEPG and uIFE. However, non-linearity of the assay, the expense of repeat determinations due to the narrow measuring ranges, and frequent antigen excess checks were found to be limitations of the sFLC assay in this study. Conclusion The FLC ratio is a more sensitive method than uIFE in the detection of monoclonal light chains and may substantially reduce the need for onerous 24 h urine collections. Our proposed algorithm for the evaluation of monoclonal gammopathy incorporates the sFLC assay, resulting in a reduction in the performance of labour intensive sIFE and uEPG + uIFE while still increasing the detection of monoclonal proteins.

scholarly journals Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Aurélie Grados ◽  
Mikael Ebbo ◽  
José Boucraut ◽  
Frédéric Vély ◽  
Pierre Aucouturier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Light Chain ◽  
Lupus Erythematosus ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Related Disease ◽  
Serum Free Light Chain ◽  
Igg4 Related Disease

Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that theκ() andλ() free light chains and theκ : λratio () are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase ofκandλfree light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.

Verification of serum reference intervals for free light chains in a local South African population

2013 ◽  
Vol 66 (11) ◽  
pp. 992-995
Author(s):  
Annalise E Zemlin ◽  
Megan A Rensburg ◽  
Hayley Ipp ◽  
Jurie J Germishuys ◽  
Rajiv T Erasmus
Keyword(s):  
Serum Protein ◽  
Light Chain ◽  
Reference Interval ◽  
Reference Intervals ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Normal Limits

Monoclonal serum free light chain measurements are used to follow up and manage patients with monoclonal gammopathies, and abnormal serum free light chain ratios are associated with risk of progression in certain diseases. We aimed to validate the reference intervals in our population. Reference intervals for κ and λ free light chains were established on 120 healthy adults. Creatinine levels were measured to exclude renal dysfunction and serum protein electrophoresis was performed. All creatinine values were within normal limits. After exclusion of subjects with abnormal serum protein electrophoreses, 113 subjects were available for analysis. The 95% reference interval was 6.3–20.6 mg/L for κ free light chains, 8.7–25.9 mg/L for λ free light chains and 0.46–1.23 for free light chain ratio. Most of the values fell within the manufacturer's recommended limits and therefore could be used for our population.

Peripheral blood B cell labeling indices are a measure of disease activity in patients with monoclonal gammopathies.

1988 ◽  
Vol 6 (6) ◽  
pp. 1041-1046 ◽  
Author(s):  
T E Witzig ◽  
N J Gonchoroff ◽  
J A Katzmann ◽  
T M Therneau ◽  
R A Kyle ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
Disease Activity ◽  
Light Chain ◽  
Peripheral Blood ◽  
Cell Labeling ◽  
Inactive Disease ◽  
Monoclonal Protein ◽  
Clinical Criteria ◽  
Monoclonal Gammopathies

Labeling indices (LI) provide a rapid measure of the bone marrow (BM) plasma cell proliferation rate and are useful in the diagnosis and prognosis of monoclonal gammopathies. Because circulating B cells may be a part of the neoplastic clone, we examined peripheral blood B cells that were producing the same cytoplasmic light chain isotype as the patient's monoclonal; protein (M-protein) and determined the peripheral blood LI (PBLI) by a two-color immunofluorescence bromodeoxyuridine method. The 105 patients studied were divided into three disease activity groups by standard clinical criteria. Median PBLI was 0.2% for the 29 patients with inactive monoclonal gammopathies (monoclonal gammopathy of undetermined significance [MGUS] and smoldering multiple myeloma [SMM]), 0.8% for the 35 patients with new, untreated multiple myeloma (MM), and 1.7% for the 41 patients with relapsed MM. These differences between groups were statistically significant (P less than .001, Wilcoxon). Four patients had high PBLI but clinically inactive gammopathy at the time of study, and all developed active MM within 6 months that required treatment. In 92 patients a BMLI was performed simultaneously with the PBLI (rank correlation coefficient, 0.69). In patients with new, untreated MM, use of both tests identified 72% of patients (23 of 32) with high LI, rather than 56% (18 of 32) by BMLI alone or 63% (20 of 32) by PBLI alone. These results suggest that PB B cells bearing the same cytoplasmic light chain isotype as the monoclonal protein are part of the malignant clone and can be kinetically active. The LI of these cells can provide a measure of disease activity and may help to differentiate active from inactive disease.

A Striking Reduction of Monoclonal Protein in a Patient with Concurrent Plasma Cell Dyscrasia and CMML-2, after Treatment with Rigosertib (01910.Na)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5362-5362
Author(s):  
Jamile M. Shammo ◽  
Agne Paner ◽  
MV Ramana Reddy ◽  
Rachel L Mitchell ◽  
Parameswaran Venugopal
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Total Protein ◽  
Light Chains ◽  
Plasma Cell Dyscrasia ◽  
Kappa Light Chain ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Kappa Light Chains

Abstract Rigosertib (ON 01910.Na) is a member of a broader class of unsaturated sulfone kinase inhibitors capable of inducing profound mitotic spindle abnormalities, abnormal centrosome localization, G2-M cell cycle phase arrest and mitotic catastrophe, culminating in apoptosis. Rigosertib is a Ras mimetic that interferes with phosphoinositide 3-kinase (PI-3K)/Akt, reactive oxygen species and Ras/Raf/polo-like kinase (PLK) signaling pathways. Although broadly cytotoxic against malignant cells, it is remarkably non-toxic for non-neoplastic cells. For this reason, this is a particularly attractive compound to test against neoplastic diseases of the bone marrow such as MDS and acute leukemia. This is a report of an unexpected reduction in monoclonal IgG, during a subject participation in a Phase III, randomized study of rigosertib, in patients with MDS who have either failed to respond, or progressed after receiving hypomethylating agents (ONTIME Trial). A 75-year-old man with CMML-2 had a CBC on day 1 of the trial that demonstrated leukocytosis, with absolute monocytosis, 7% blasts in the peripheral blood, Hgb of 9.4 gm/dl, and platelets of 7 K. He was transfusion dependent for both pRBCs and platelets. His chemistry panel demonstrated a high total protein of 9.9 (NL: 6.0 - 8.2 G/DL) with low albumin at 2.4 (NL: 3.5 - 5.0 G/DL); therefore, an SPEP/IPEP was performed, reporting the presence of monoclonal IgG kappa. Quantitative immunoglobulins showed an elevated IgG of 3594 mg/dl (NL: 596 - 1584 MG/DL). Serum free light chains were remarkable for an elevated Kappa fraction at 38.94 (NL: 0.33 - 1.94 MG/DL). On day 1 of cycle 5 of rigosertib, he was started on pulse decadron for 2 months, after which his disease progressed to AML, and he died shortly thereafter. Neither his bone marrow biopsies, nor his hematological parameters demonstrated a response to treatment with rigosertib. In contrast and interestingly, his total protein, serum kappa light chain load, and total IgG, all were drastically reduced shortly after initiation of rigosertib, as can be seen in the graph below depicting a substantial drop in his kappa light chain as well as the kappa/light chain ratio. Importantly, reduction in the monoclonal protein was noted prior to initiation of pulse decadron. Even though his initial bone marrow biopsy did not note a monoclonal plasma cell population, a subsequent bone marrow reported a low-level involvement with a plasma cell dyscrasia, with kappa light chain restriction. His final bone marrow biopsy confirmed progression to AML, but the previously seen plasma cell dyscrasia was no longer present. Conclusion: We are not aware of prior reports describing a similar effect of rigosertib on M-proteins. However, in vitro studies with rigosertib have demonstrated antitumor effects and induction of apoptosis in myeloma cell lines1. This observation merits further exploration of this agent in multiple myeloma. References: 1. Reddy MV, et al. Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON01910.Na): Synthesis, Structure-Activity Relationship, and Biological Activity. J Med Chem, 2011, 54(18):6254-76. Figure 1. Decrease in serum free kappa light chains following initiation of rigosertib. Figure 1. Decrease in serum free kappa light chains following initiation of rigosertib. Figure 2. Decrease in kappa/lambda ratio following initiation of rigosertib. Figure 2. Decrease in kappa/lambda ratio following initiation of rigosertib. Disclosures Shammo: Onconova: Research Funding.

The Relationship Between Serum Free Light Chain Levels and Urine Protein in Patients with IgG or IgA Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1810-1810
Author(s):  
J. Mehta ◽  
E. Vickrey ◽  
D. Ramadurai ◽  
E. Voigt ◽  
C. Fitzpatrick ◽  
...  
Keyword(s):  
Light Chain ◽  
Gold Standard ◽  
Free Light Chain ◽  
Light Chains ◽  
Urine Collection ◽  
Urine Protein ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
The Relationship

Abstract Abstract 1810 Poster Board I-836 The serum free light chain (SFLC) assay is often though to be a replacement for the cumbersome process of 24-hour urine collection for monoclonal protein estimation (http://www.freelite.co.uk/initialinvestigationpro-24.asp; accessed 16 July 2009) despite evidence suggesting that SFLC estimation cannot replace urine protein quantification (Singhal et al. Blood 2007; 109:3611-2). We studied results from patients with IgG or IgA myeloma if all the following criteria were satisfied: concomitant SFLC and 24-hour urine specimens analyzed, no oligoclonal proteins, no diminished free light chain levels (involved or uninvolved). The aim was to study the correlation between SFLC and 24-hour urine total protein (24UTP), 24-hour urine monoclonal protein (24UMP) and urine immunofixation electrophoresis (UIFE). Only concordant abnormal SFLC ratios were considered abnormal (Singhal et al. Blood 2009; 114:38-9). 558 samples in 114 patients were identified. SFLC ratio was abnormal in 242 and normal in 316 (including 2 discordant abnormal). UIFE (available in 540) was negative in 290. The proportion of samples with normal SFLC ratio decreased as 24UTP increased (P<0.001): ≤200 mg - 75% of 243, 200-500 mg 33% of 129, 501-1000 mg - 24% of 54, and >1000 mg - 6% of 32. Similarly, the proportion of samples with normal SFLC ratio declined as 24UMP increased (P=0.001): ≤200 mg (including negative) - 41% of 145, 200-500 mg 4% of 28, 501-1000 mg - 0% of 14, and >1000 mg - 0% of 15. SFLC ratio was normal in 84% of samples with negative UIFE and in 26% of samples with positive UIFE (P<0.0001). Among the 47 samples with abnormal SFLC ratio and negative UIFE, the 24UTP was 47-288 mg (median 112). 24UMP was 35 mg in 1, “faint” in 1, and no restricted bands were seen in ther remaining 45. The table shows the relationship between UPEP, UIFE and SFLC amongst the 540 samples where all 3 tests were available. The presence of any restricted band on UPEP, even if too small to quantify, was considered positive. n=540 Positive UPEP Negative UPEP Positive UIFE Negative UIFE Positive UIFE 222 28 Negative UIFE 17 273 Abnormal SFLC ratio 172 59 184 47 Normal SFLC ratio 67 242 66 243 If a positive UPEP is considered the “gold standard” evidence of the presence monoclonal light chains in the urine, the sensitivity of UIFE in detecting urine monoclonal protein is 93% and that of an abnormal SFLC ratio is 72%. On the other hand, if a positive UIFE is considered the “gold standard” evidence of monoclonal light chains in the urine, the sensitivity of an abnormal SFLC ratio in detecting urine monoclonal protein is 74%. These data, obtained from a much large number of homogeneous clinical samples, confirm our previous observations (Singhal et al. Blood 2007; 109:3611-2) that an abnormal SFLC ratio cannot consistently predict the presence of either non-specific or monoclonal proteinuria. Fortunately, the proportion of urine samples with large aounts of non-specific or monoclonal proteinuria that is associated with normal SFLC ratios is small. The sensitivity of the SFLC ratio in detecting urine monoclonal protein is less than that of UIFE. The SFLC assay cannot replace 24-hour urine collection in clinical practice without compromising patient care. Whether a less cumbersome technique such as a spot (random) urine protein-creatinine ratio - used in conjunction with the SFLC assay - can avert the need for 24-hour urine collections in myeloma patients remains to be investigated. Disclosures No relevant conflicts of interest to declare.

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