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

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.

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 &gt;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 &lt;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.

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.

Serum and Urine Protein Electrophoresis and Serum-Free Light Chain Assays in the Diagnosis and Monitoring of Monoclonal Gammopathies

2020 ◽  
Vol 5 (6) ◽  
pp. 1358-1371
Author(s):  
Gurmukh Singh
Keyword(s):  
Light Chain ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Urine Protein ◽  
Serum Free ◽  
Monoclonal Gammopathies ◽  
Serum Free Light Chain ◽  
Serum Free Light Chains

Abstract Background Laboratory methods for diagnosis and monitoring of monoclonal gammopathies have evolved to include serum and urine protein electrophoresis, immunofixation electrophoresis, capillary zone electrophoresis, and immunosubtraction, serum-free light chain assay, mass spectrometry, and newly described QUIET. Content This review presents a critical appraisal of the test methods and reporting practices for the findings generated by the tests for monoclonal gammopathies. Recommendations for desirable practices to optimize test selection and provide value-added reports are presented. The shortcomings of the serum-free light chain assay are highlighted, and new assays for measuring monoclonal serum free light chains are addressed. Summary The various assays for screening, diagnosis, and monitoring of monoclonal gammopathies should be used in an algorithmic approach to avoid unnecessary testing. Reporting of the test results should be tailored to the clinical context of each individual patient to add value. Caution is urged in the interpretation of results of serum-free light chain assay, kappa/lambda ratio, and myeloma defining conditions. The distortions in serum-free light chain assay and development of oligoclonal bands in patients‘ status post hematopoietic stem cell transplants is emphasized and the need to note the location of original monoclonal Ig is stressed. The need for developing criteria that consider the differences in the biology of kappa and lambda light chain associated lesions is stressed. A new method of measuring monoclonal serum-free light chains is introduced. Reference is also made to a newly defined entity of light chain predominant intact immunoglobulin monoclonal gammopathy. The utility of urine testing in the diagnosis and monitoring of light chain only lesions is emphasized.

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.

scholarly journals Serum free light chain measurements to reduce 24-h urine monitoring in patients with multiple myeloma with measurable urine monoclonal protein

2018 ◽  
Vol 93 (10) ◽  
pp. 1207-1210 ◽  
Author(s):  
Marcella Tschautscher ◽  
Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Lacy ◽  
Morie Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain

scholarly journals Quantitative Immunoprecipitation Free Light Chain Mass Spectrometry (QIP-FLC-MS) Simplifies Monoclonal Protein Assessment and Provides Added Clinical Value in Systemic AL Amyloidosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4375-4375 ◽  
Author(s):  
Faye Amelia Sharpley ◽  
Hannah Victoria Giles ◽  
Richa Manwani ◽  
Shameem Mahmood ◽  
Sajitha Sachchithanantham ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Light Chain ◽  
Residual Disease ◽  
Renal Involvement ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Free Light Chains ◽  
Accurate Identification ◽  
Monoclonal Protein ◽  
Serum And Urine

Introduction Early diagnosis, effective therapy and precise monitoring are central for improving clinical outcomes in systemic light chain (AL) amyloidosis. Diagnosis and disease response assessment is primarily based on the presence of monoclonal immunoglobulins and free light chains (FLC). The ideal goal of therapy associated with best outcomes is a complete responses (CR), defined by the absence of serological clonal markers. In both instances, detection of the monoclonal component (M-component) is based on serum FLC assessment together with traditional serum and urine electrophoretic approaches, which present inherent limitations and lack sensitivity particularly in AL where the levels are typically low. Novel mass spectrometry methods provide sensitive, accurate identification of the M-component and may prove instrumental in the timely management of patients with low-level amyloidogenic light chain production. Here we assess the performance of quantitative immunoprecipitation FLC mass spectrometry (QIP-FLC-MS) at diagnosis and during monitoring of AL amyloidosis patients treated with bortezomib-based regimens. Methods We included 46 serial patients with systemic AL amyloidosis diagnosed and treated at the UK National Amyloidosis Centre (UK-NAC). All patients had detailed baseline assessments of organ function and serum FLC measurements. Baseline, +6- and +12-month serum samples were retrospectively analysed by QIP-FLC-MS. Briefly, magnetic microparticles were covalently coated with modified polyclonal sheep antibodies monospecific for free kappa light chains (anti-free κ) and free lambda light chains (anti-free λ). The microparticles were incubated with patient sera, washed and treated with acetic acid (5% v/v) containing TCEP (20 mM) in order to elute FLC in monomeric form. Mass spectra were acquired on a MALDI-TOF-MS system (Bruker, GmbH). Results were compared to serum FLC measurements (Freelite®, The Binding Site Group Ltd), as well as electrophoretic assessment of serum and urine proteins (SPE, sIFE, UPE and uIFE). Results Cardiac (37(80%) patients) and renal (31(67%) patients) involvement were most common; 25(54%) patients presented with both. Other organs involved included liver (n=12), soft tissue (n=4), gastrointestinal tract (n=3) and peripheral nervous system (n=2). Baseline Freelite, SPE, sIFE and uIFE measurements identified a monoclonal protein in 42(91%), 22(48%), 34(74%) and 21(46%) patients, respectively. A panel consisting of Freelite + sIFE identified the M-component in 100% of the samples. QIP-FLC-MS alone also identified an M-component in 100% of the samples and was 100% concordant with Freelite for typing the monoclonal FLC (8 kappa, 34 lambda). In 4 patients, QIP-FLC-MS identified an additional M-protein that was not detected by the other techniques. In addition, 4/8(50%) kappa and 4/38(11%) lambda patients showed a glycosylation pattern of monoclonal FLCs at baseline by mass spectrometry. Interestingly, the frequency of renal involvement was significantly lower for patients with non-glycosylated forms (25% vs 76%, p=0.01), while no similar relationship was found for any other organs. During the 1-year follow-up period, 17 patients achieved a CR; QIP-FLC-MS identified serum residual disease in 13(76%) of these patients. Conclusion In our series, QIP-FLC-MS was concordant with current serum methods for identifying the amyloidogenic light chain type and provided, against all other individual tests, improved sensitivity for the detection of the monoclonal protein at diagnosis and during monitoring. The ability to measure the unique molecular mass of each monoclonal protein offers clone-specific tracking over time. Glycosylation of free light chains is over-represented in AL patients which may allow earlier diagnosis and better risk-assessment of organ involvement. Persistence of QIP-FLC-MS positive M component in patients otherwise in CR may allow targeted therapy. Overall, QIP-FLC-MS demonstrates potential to be exploited as a single serum test for precise serial assessment of monoclonal proteins in patients with AL amyloidosis. Disclosures Wechalekar: GSK: Honoraria; Janssen-Cilag: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Celgene: Honoraria.

Lambda monoclonal free light chain abnormalities detected by a serum immunofixation electrophoresis assay are underrepresented by quantitative serum free light chain results

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Rebecca Treger ◽  
Kathleen Hutchinson ◽  
Andrew Bryan ◽  
Chihiro Morishima
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Sample Population ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Immunofixation Electrophoresis ◽  
High Concordance ◽  
Polyclonal Antisera

Abstract Protein and immunofixation (IFIX) electrophoresis are used to diagnose and monitor monoclonal gammopathies. While IFIX detects clonal production of intact immunoglobulins and free light chains (FLC), the latter can also be quantified using a serum free light chain (SFLC) assay, in which polyclonal antisera detects epitopes specific for free kappa (KFLC) or lambda light chains (LFLC). An abnormal KFLC: LFLC ratio (KLR) serves as a surrogate for clonality. While the SFLC assay is highly sensitive, normal LFLC (&lt;2.63mg/dL) and KLR results (&gt;0.26 & &lt;1.65) were found in samples with distinct lambda monoclonal free light chains visualized by IFIX (X-LMFLC). To investigate this discordance, contemporaneous SFLC or KLR values were evaluated for their ability to accurately classify monoclonal FLCs identified by IFIX. We performed a retrospective analysis of serum and urine IFIX (Sebia Hydrasys) and SFLC (Freelite®, Binding Site) results from our institution between July 2010 through December 2020, using R 4.0.2 and Tidyverse packages. From among 9,594 encounters in which a single monoclonal component was initially identified by IFIX, 157 X-LMFLC and 131 X-KMFLC samples were analyzed. Elevated LFLC with normal KFLC was identified in 105/157 X-LMFLC samples (67%), while both LFLC and KFLC were elevated in 42/157 samples (27%). Concordance between X-KMFLC and KFLC was markedly higher, where 122/131 samples (93%) displayed elevated kappa FLC (&gt;1.94mg/dL) with normal LFLC, and only 7/131 X-KMFLC samples (5%) possessed both elevated KFLC and LFLC. The use of KLR to identify pathogenic monoclonal free light chains improved lambda concordance to 85%; however, 19/157 (12%) of X-LMFLC samples still exhibited normal KLR. High concordance of 98% was again observed for X-KMFLC with abnormal KLR. When samples were segregated according to normal or impaired renal function (eGFR &gt; or ≤60mL/min/1.73m², respectively), this disparate identification of X-LMFLC and X-KMFLC by the SFLC assay persisted, suggesting that renal dysfunction (as measured by eGFR) does not underlie this phenomenon. Lastly, we corroborated the above findings in a larger sample population by examining patients with urine Bence Jones FLC identified by IFIX who had free or intact monoclonal components in serum (N=724), grouped by lambda or kappa light chain involvement. The cause(s) of the discrepant performance by the Freelite® SFLC assay, relative to the Sebia Hydrasys IFIX assay, for identifying lambda FLC components is currently unclear. Possible contributory factors include assay reference range cutoffs, other patient disease parameters, and differences in assay-specific polyclonal antisera. Future analyses of these factors will help to further characterize SFLC assay performance and elucidate how interpretation of composite serum FLC test results can be improved to better guide patient management.

Treatment of Relapsed Myeloma in a Patient With Renal Insufficiency

2018 ◽  
Vol 36 (20) ◽  
pp. 2012-2016
Author(s):  
Joan Bladé ◽  
Laura Rosiñol ◽  
María Teresa Cibeira ◽  
Carlos Fernández de Larrea
Keyword(s):  
Serum Creatinine ◽  
Light Chain ◽  
Progressive Disease ◽  
M Protein ◽  
Bone Lesions ◽  
High Dose ◽  
Kappa Light Chain ◽  
Urine Protein ◽  
Urine Protein Excretion ◽  
Protein Excretion

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old man was diagnosed in March 2010 with stage III immunoglobulin G kappa multiple myeloma (MM) after presenting with bone pain as a result of multiple lytic bone lesions and T12 vertebral collapse. Laboratory work-up showed a serum M protein of 72 g/L and a 24-hour kappa light-chain urine protein excretion of 730 mg, hemoglobin of 10.2 g/dL, serum albumin of 49 g/L, serum β2-microglobulin of 6.4 mg/L, serum creatinine level of 1.6 mg/dL with an estimated glomerular filtration rate (eGFR) of 47 mL/min/1.73 m2, and normal serum calcium and lactate dehydrogenase (LDH) levels. His bone marrow contained 58% plasma cells, which showed the 17p deletion abnormality (Fig 1). He was treated with vertebroplasty and alternating chemotherapy with carmustine, vincristine, cyclophosphamide, melphalan, and prednisone and vincristine, carmustine, doxorubicin and dexamethasone. Because of progressive disease, salvage therapy with bortezomib and dexamethasone was administered with no response. The patient was then switched to lenalidomide and dexamethasone, which yielded minimal response. He underwent autologous stem-cell transplantation (ASCT) with melphalan 200 mg/m2 as high-dose therapy in February 2011, which led to a partial response, but in December 2011, progressive disease was documented, and the patient was enrolled in a clinical trial of carfilzomib monotherapy, with stable disease for 33 cycles. In October 2014 serum M protein rose to 38.6 g/L, with 24-hour kappa light-chain urine protein excretion of 840 mg, serum creatinine of 2.1 mg/dL, and an eGFR of 41 mL/min/1.73 m2. He presented to discuss ongoing treatment options.

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