scholarly journals Evaluation of the Impact of Renal Failure on Correlation and Concordance Between 2 Free Light Chain Assays

2016 ◽  
Vol 16 (12) ◽  
pp. 693-704 ◽  
Author(s):  
Caroline Moreau ◽  
Brice Autier ◽  
Thibault Cavey ◽  
Emmanuel Rouger ◽  
James Norwood ◽  
...  
Keyword(s):  
Renal Failure ◽  
Light Chain ◽  
Free Light Chain ◽  
The Impact

Improving Outcomes in Patients with Renal Failure Secondary to Multiple Myeloma: Results From ChAR2M2.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1875-1875
Author(s):  
Colin Hutchison ◽  
Parisa Airia ◽  
Mark Cook ◽  
Daniel Grima
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Side Effects ◽  
Light Chain ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Treatment Patterns ◽  
Free Light Chain ◽  
High Rate ◽  
Sustained Reduction

Abstract Abstract 1875 Poster Board I-900 Study purpose: To explore how free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) has been adopted into clinical practice for the management of renal failure secondary to multiple myeloma. Describing treatment patterns and the laboratory and clinical outcomes associated with its use. Methods: A chart audit of patients treated with FLC removal by HCO-HD, using the Gambro HCO 1100 dialyser, was performed in 16 dialysis centers across 9 countries. Patient demographics, treatment patterns and dialysis side-effects were recorded. In addition, the following outcomes were measured: dialysis independence and reductions in serum FLCs concentrations at 12 and 21 days. Results: Data for 66 patients was entered. Patients had an average age of 65.1 (SD×10.1); 42 of them (63.64%) were male and 24 (36.36%) were female. Sixteen (24%) presented with relapsing myeloma and 50 (76%) had de novo disease. On average, each patient received 13 HCO-HD sessions (SD×8). Forty-one patients became dialysis independent (62.12%), after an average of 12 sessions. Dialysis related side-effects were reported in 6% of all patients. Forty patients (60.61%) were reported to have a sustained reduction in serum FLC concentrations by day 12. By day 21 this had increased to forty-one (62.12%). Among the patients who achieved a sustained reduction in serum FLC concentrations, 28 (70%) had a decline in FLC levels of more than 50% by day 12 and 34 (82.93%) by day 21. Among patients who achieved sustained reduction of more than 50% in serum FLC concentrations by day 12, 75% became dialysis independent. In comparison only 53% of those with a reduction of less than 50% became dialysis independent (p×0.007). Furthermore, among patients who achieved sustained FLC reduction of greater than 75%, 81% became dialysis independent. The rate of dialysis independence was also significantly higher in patients with de novo disease compared with those with relapsing myeloma (64% versus 56%, p×0.04). Conclusion: Free light chain removal by HCO-HD was well tolerated and associated with a very high rate of dialysis independence in patients with renal failure secondary to multiple myeloma. Rates of renal recovery were greater in patients with de novo myeloma and those who achieved an early reduction in serum FLC concentrations. Disclosures: No relevant conflicts of interest to declare.

Impact of Normalized Free Light Chain Ratio for Assessment of Monoclonal Protein in Patients with Light Chain Only and Oligosecretory Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2074-2074
Author(s):  
Kentaro Narita ◽  
Yoshiaki Usui ◽  
Yoshiaki Abe ◽  
Masami Takeuchi ◽  
Kosei Matsue
Keyword(s):  
Light Chain ◽  
Urine Analysis ◽  
Residual Disease ◽  
Response Assessment ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Reference Ranges ◽  
Immunofixation Electrophoresis ◽  
The Impact ◽  
Monoclonal Component

Abstract Background: Monitoring of serum free light chain (sFLC) ratio after treatment in multiple myeloma (MM) patients is valuable for assessing monoclonal component of free light chain (FLC). However, the recent International Myeloma Working Group guidelines did not recommend replacing 24-hour urine analysis with FLC analysis in diagnosis or response assessment of MM, and previous studies indicated discordance between urine analysis and sFLC levels in light chain-only MM (LCMM). This is clinically relevant because sFLC normalization was considered a surrogate for improved outcome in both LCMM and intact immunoglobulin MM (IIMM). The clinical impact of FLC ratio normalization on detection of monoclonal component may differ between LCMM or oligosecretory myeloma (OSMM) and IIMM. This study explored the utility of sFLC ratio as a surrogate for residual clonal monoclonal component compared with 24-hour urine immunofixation electrophoresis (uIFx) after treatment. We evaluated the impact of normalization of sFLC ratio in patients with LCMM/OSMM that obtained very good partial response (VGPR), complete response (CR), and immunophenotypic CR (iCR; sIFx/uIF negative plus ≤ 10-4 clonal PCs) determined by multicolor flow cytometry (MFC). Methods: We included 176 patients (51 with LCMM and OSMM, 125 with IIMM) treated between April 2006 and January 2016 at Kameda Medical Center, Japan. Immunoglobulin levels in serum and urine samples were examined by serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (sIFx), urine protein electrophoresis (UPEP), uIFx, and sFLC for response assessment. Minimal residual disease (MRD) assessments after treatment were performed by 6-color MFC and the results were compared to other tests of monoclonal components, including SPEP, UPEP, sIFx, uIFx, and FLC. Agreement between sFLC normalization and MRD by MFC was assessed using kappa statistic. Disease response was evaluated using IMWG criteria. sFLC was measured by Fleelite® assay (The Binding Site Group Ltd.). Reference ranges for sFLC have been previously published. Statistical analyses were performed with EZR, which is a graphical user interface for R ver. 3.2.1. Ethical considerations: This study was approved by the local ethics committee and conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. Results: All of 51 LCMM/OSMM patients (100%) and 95 of the 125 IIMM patients (72%) had measurable and abnormal involved sFLC (≥ 100 mg/L) and positive uIFx at presentation. VGPR, CR, and iCR were obtained in 31 (61%), 25 (49%), and 14 (27%) patients with LCMM/OSMM, respectively, and normalization of sFLC ratio at VGPR, CR and iCR was seen in 1/31 (3%), 13/25 (48%), and 8/14 (57%) of these patients, respectively. Among the LCMM/OSMM patients with iCR, 4 patients obtained deeper iCR (≤ 10-5 clonal PCs) and all of them had normal sFLC ratio, while sFLC ratio remained abnormal in the rest of 10 iCR patients that did not achieve deeper iCR. In IIMM patients, VGPR, CR, and iCR were obtained in 78 (61%), 52 (42%), and 20 (16%) patients, respectively. In contrast to the LCMM/OSMM patients, normalization of the sFLC ratio at VGPR, CR, and iCR was seen in 52/78 (67%), 39/52 (75%), and 17/20 (85%) of IIMM patients, respectively. Thirteen of the 14 IIMM patients (93%) that obtained deeper iCR had normal sFLC ratio. Among the patients with IIMM, percentage of patients with normalized sFLC ratio did not differ between the response groups (p=0.11), while it was significantly different in LCMM/OSMM patients (p<0.001) (Figure 1). These observations indicated that the normalization of sFLC ratio is significantly associated with deeper response in LCMM/OSMM patients, but not in IIMM patients. Conclusions: Our observations indicated that sFLC test has greater sensitivity than urine immunofixation for detection of the monoclonal component of sFLC, especially in patients with LCMM/OSMM. In addition, we also showed that normalization of sFLC ratio is correlated with the depth of response assessed by MFC in patients with LCMM/OSMM, but not in IIMM patients. These findings suggest that FLC ratio provides greater sensitivity for residual disease monitoring than uPEP or uIFx in patients with LCMM and OSMM, and therefore could be considered as an alternative to urine analysis for monitoring of LCMM/OSMM patients. Disclosures No relevant conflicts of interest to declare.

Extent of Hematologic Response Is Important in Determining Outcome in Transplanted Patients with Primary Amyloidosis AL. Importance of Achieving CR.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 611-611
Author(s):  
Morie Abraham Gertz ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
Shaji K. Kumar ◽  
...  
Keyword(s):  
Light Chain ◽  
Objective Response ◽  
Complete Response ◽  
Free Light Chain ◽  
Cell Transplant ◽  
Landmark Analysis ◽  
Hematologic Response ◽  
Peripheral Nerve Involvement ◽  
The Impact ◽  
Serum And Urine

Abstract INTRODUCTION Stem cell transplant has been increasingly used in the initial therapy of newly diagnosed systemic AL. Introduction of the free light chain assay has made it easier to quantify responses in patients with AL. It is unclear whether the goal of therapy should be a hematologic response or, as in multiple myeloma, a complete response. This paper addresses the impact of the degree of response on outcome. PATIENTS AND METHODS 282 consecutively transplanted patients are included in this analysis. None of the patients were excluded. There were 169 men (59%). 28% of the cohort have died. 69% had renal involvement, 51% cardiac involvement, 11% peripheral nerve involvement, 16% hepatic involvement. The median percentage of plasma cells at the time of transplant was 7. Echocardiographic analysis revealed a median septal thickness of 12 and a median ejection fraction of 65%. Patients ranged in age from 31 to 71 with a median of 57 years and were transplanted at a median of 4.2 months following histologic diagnosis of amyloidosis. 27% of patients received reduced intensity conditioning usually due to moderate cardiomyopathy or renal insufficiency. 201 patients achieved a hematologic response and 93 of these achieved a complete response. The criteria for response were reported in accord with the consensus definition for response established at The Xth International Symposium on Amyloid and Amyloidosis. A complete response required immunofixation negativity of serum and urine with a normal free light chain ratio. A hematologic objective response required a 50% reduction of serum and urine monoclonal protein with a 50% reduction in the free light chain value. Figure 1 shows the Kaplan Meier curves demonstrating the survival of all patients based on whether they achieved a complete response, partial response, or failed to achieve response. There were 93 CR, 108 PR, and 81 nonresponders. The differences in all three curves are significant at P&lt;.001. Figure 2 demonstrates the same cohort of patients using a six month landmark analysis to exclude the effect of treatment related mortality on outcome. There were 86 CR, 91 PR, and 36 NR for a total of 213 patients. There was a difference in response rate based on conditioning intensity (p&lt;0.01) and age (p=0.046). The median survival was only reached in the NR at 40.1 months and, in the landmark analysis the differences between all three survival curves were statistically significant. CONCLUSION Patients who achieve a hematologic complete response following sct for AL do better than other patients. Patients who achieve an objective response have a superior outcome than patients who fail to achieve a hematologic response, in a landmark analysis at six months. It is unclear if consolidation chemotherapy should be offered to partial responders in an attempt to convert them into CR’s. Figure Figure Figure Figure

scholarly journals Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure

2008 ◽  
Vol 9 (1) ◽  
Author(s):  
Colin A Hutchison ◽  
Tim Plant ◽  
Mark Drayson ◽  
Paul Cockwell ◽  
Melpomeni Kountouri ◽  
...  
Keyword(s):  
Renal Failure ◽  
Light Chain ◽  
Free Light Chain ◽  
Severe Renal Failure ◽  
Serum Free ◽  
Serum Free Light Chain

The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
Giovanni Palladini ◽  
Paolo Milani ◽  
Andrea Foli ◽  
Marco Basset ◽  
Francesca Russo ◽  
...  
Keyword(s):  
Renal Failure ◽  
Light Chain ◽  
Clinical Performance ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Al Amyloidosis ◽  
Interference Factor ◽  
Prognostic Assessment ◽  
Response To Chemotherapy ◽  
The Impact

AbstractThe measurement of circulating free light chains (FLC) is of utmost importance in immunoglobulin light chain (AL) amyloidosis, being a fundamental part of the diagnostic workup, prognostic stratification and assessment of response to therapy. Renal failure is a common feature of AL amyloidosis and can considerably affect the concentration of FLC.We assessed the impact of renal failure on the clinical performance of the Freelite assay in 982 consecutive, newly diagnosed patients with AL amyloidosis, 822 with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 mThe diagnostic sensitivity of the κ/λ FLC ratio was lower for λ amyloidogenic FLC in patients with renal failure (81% vs. 60%, p<0.001) and the FLC concentration had no independent prognostic significance in patients with severe renal dysfunction. However, FLC response to chemotherapy could still discriminate patients with better outcome.Renal failure is a relevant interference factor when using the Freelite assay for the identification of the amyloidogenic light chain and for prognostic assessment in patients with AL amyloidosis and renal failure.

P1114HA-130 HEMOPERFUSION CARTRIDGE IN THE TREATMENT OF CAST NEPHROPATHY IN A 58-YEAR-OLD MALE WITH MULTIPLE MYELOMA: A CASE REPORT

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Joanna Margarita Santos ◽  
Maria Kristina L Alolod
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Case Report ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Cast Nephropathy ◽  
History Of

Abstract Background and Aims Multiple myeloma is a plasma cell neoplasm that results in the production of monoclonal immunoglobulin. Renal failure is a common complication of multiple myeloma, occurring in approximately one-half of patients on initial presentation and is associated with increased mortality. Cast nephropathy in particular, is considered to be one of the major mechanisms of renal failure in multiple myeloma, and is characterized by precipitation of free light chains in the distal nephron, leading to intratubular obstruction, inflammation and fibrosis. Recent studies have demonstrated the use of extracorporeal methods such as plasmapheresis and high-cutoff membrane dialysis as an adjunctive therapy to chemotherapy in the management of cast nephropathy, however currently there are no existing guidelines in the use of extracorporeal therapies in the management of complications of multiple myeloma. Hemoperfusion is an extracorporeal treatment technique which utilizes adsorption in the removal of specific toxins. The HA 130 cartridge in particular has a resin pore size distribution of 500Da- 40 KDa and is able to remove molecules at 5-30kDa. In this case report we describe the use of HA 130 hemoperfusion cartridge in the treatment of cast nephropathy in Multiple Myeloma. Method A 58-year-old male, diabetic, non-hypertensive came in for 5-day history of generalized body weakness, associated with myalgia, lumbar pain and undocumented fever, with 1-day history of loose stools and vomiting. Upon admission blood tests done revealed anemia with a hemoglobin of 7.8g/dl, creatinine of 9.97mg/dL and potassium of 5.5mmol/L. He was diagnosed with acute renal failure and underwent hemodialysis on the second hospital day. On workup he had lytic bone lesions in the spine, pelvis and cranium on CT scan and x-ray. Serum Protein Electrophoresis (SPEP) and Serum Free Light Chain (sFLC) tests showed a monoclonal gammopathy. Serum beta 2 microglobulin was elevated at 12,618ng/ml. Free kappa and lambda light chains were also elevated at 19,250mg/L and 25.7mg/L, respectively. Bone marrow biopsy was done, with findings of markedly hypercellular marrow with 80% plasma cells confirming the diagnosis of Multiple Myeloma. Combined hemodialysis with hemoperfusion were done using HA 130 filter and hi flux dialyzer for 2.5 hours then hemodialysis for three times a week. Patient was also started on chemotherapy using Bortezomib with Dexamethasone for 2 cycles. Results Patient had a total of 14 sessions of combined hemoperfusion with hemodialysis. On repeat free kappa light chains decreased to 212.5mg/L. Patient was maintained on hemodialysis three times a week and was discharged after 55 hospital days. Outpatient hemodialysis was continued three times a week, and after 2 weeks, patient showed signs of renal recovery with a repeat creatinine of 2.1mg/dL. Four weeks after discharge, patient was independent of hemodialysis with a repeat creatinine of 1.3mg/dL. Conclusion This report highlights the use of hemoperfusion using HA 130 cartridge in combination with chemotherapy using Bortezomib in reducing free light chain levels in a 58-year-old male that developed renal failure secondary to cast nephropathy. Patient was able to achieve reduction in free light chain levels, improvement in renal function and eventually independence from hemodialysis four weeks after the last hemoperfusion treatment. Further studies using a randomized control trial on the use of hemoperfusion in directly reducing serum free light chain levels is recommended. The value of hemoperfusion on the rate of independence from hemodialysis, as well as survival rates among patients with renal failure secondary to multiple myeloma may also be worth investigating using larger studies.

scholarly journals The Value of Serum Immunoglobulin Free Light Chain Assessment in Patients with Monoclonal Gammopathies and Acute Renal Failure

2012 ◽  
Vol 29 (4) ◽  
pp. 385-391 ◽  
Author(s):  
Mustafa Cirit ◽  
Atilla Uzum ◽  
Pinar Ozen ◽  
Banu A. Senturk ◽  
Giray Bozkaya ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Immunoglobulin ◽  
Monoclonal Gammopathies

Comparison of Immunofixation, Serum Free Light Chain, and Immunophenotyping for Response Evaluation and Prognostication in Multiple Myeloma

2011 ◽  
Vol 29 (12) ◽  
pp. 1627-1633 ◽  
Author(s):  
Bruno Paiva ◽  
Joaquin Martinez-Lopez ◽  
Maria-Belen Vidriales ◽  
Maria-Victoria Mateos ◽  
Maria-Angeles Montalban ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Light Chain ◽  
Normal Serum ◽  
Free Light Chain ◽  
Multiparameter Flow Cytometry ◽  
Serum Free ◽  
Symptomatic Disease ◽  
Serum Free Light Chain ◽  
The Impact

To investigate the impact of immunophenotypic response (IR) versus complete response (CR) and CR plus normal serum free light chain (sFLC) ratio (stringent CR) in elderly patients with multiple myeloma (MM) treated with novel agents. Patients and Methods From a total of 260 elderly patients newly diagnosed with MM included in the GEM05>65y trial, 102 patients achieving at least a partial response with ≥ 70% reduction in M-component after the six planned induction cycles were simultaneously analyzed by immunofixation, sFLC, and multiparameter flow cytometry (MFC) immunophenotyping; this population is the focus of this study. Results Forty-three percent of patients achieved CR, 30% achieved stringent CR, and 30% achieved IR. Patients in stringent CR showed no significant survival advantage compared with those in CR, whereas patients in IR showed significantly increased progression-free survival (PFS) and time to progression (TTP) compared with those in stringent CR or CR; this was confirmed by multivariate analysis (hazard ratio, 4.1; P = .01 for PFS). Discrepancies between the three techniques were relatively common. Notably, in all seven patients achieving IR but remaining immunofixation positive, the M-component disappeared in follow-up analysis. In contrast, MFC-positive patients who were immunofixation negative (n = 20) showed a tendency toward early reappearance of the M-component (median, 3 months). Similarly, in five of 11 stringent CR but MFC-positive patients, symptomatic disease progression was recorded at a median of 13 months after induction. Conclusion Achieving an IR translates into superior PFS and TTP compared with conventional CR or stringent CR. These techniques provide complementary information and thus, an effort should be made to refine response criteria in MM.

Limitations of Free Light Chain Assays caused by the Matrix Effect

2020 ◽  
Vol 5 (2) ◽  
pp. 311-319
Author(s):  
Christopher W Farnsworth ◽  
Nicole M Logsdon ◽  
Jennifer E Hayes ◽  
Rehan Rais ◽  
Maria A Willrich ◽  
...  
Keyword(s):  
Binding Site ◽  
Light Chain ◽  
Matrix Effect ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Follow Up Studies ◽  
The Matrix ◽  
The Impact

Abstract Background Serum free light chain (FLC) assays are used clinically to measure the concentration of κ and λ FLC in patients with suspected or diagnosed plasma cell proliferative disorders. Previous studies have demonstrated a loss of linearity in low concentration ranges of these assays. We hypothesized that this result could be caused by a matrix effect. Methods Recovery studies were performed for κ and λ FLC in both serum and saline using the Freelite assay (Binding Site) on a Cobas c502 system (Roche). Samples were analyzed either at the recommended dilution or undiluted. Follow-up studies were performed in varying matrices ranging from 0% to 100% saline. Retrospective patient data were analyzed to assess the impact on reported κ FLC, λ FLC, and κ/λ ratio. Results FLC in a serum matrix demonstrated underrecovery relative to samples diluted in saline for both κ and λ FLC. Of 255 patient samples with λ FLC measured undiluted (λ FLC &lt;6.0 mg/L), an unexpected gap was observed in patient results between 2.0 and 6.0 mg/L. In addition, 23 patients measured serially with λ FLC between 2.0 and 6.0 mg/L demonstrated dramatic changes in κ/λ ratio, with no changes in κ FLC, likely because of the matrix effect. Conclusions The κ and λ Freelite assays exhibit a matrix effect when samples are tested undiluted, which has the potential to affect the κ/λ ratio. Consequently, our laboratory has stopped reporting λ FLC &lt;6.0 mg/L.

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