The Current Role of the Heavy/Light Chain Assay in the Diagnosis, Prognosis and Monitoring of Multiple Myeloma: An Evidence-Based Approach (original) (raw)
Related papers
Croatian medical journal, 2015
To evaluate the clinical utility of incorporating a novel heavy/light chain immunoassay (HLC) into the existing methods for the assessment of multiple myeloma (MM) patients. Convenience sera samples from 90 previously treated IgG and IgA MM patients in different disease stages were analyzed. The study was conducted in Clinical Hospital Center Zagreb between 2011 and 2013. The collected sera were analyzed by standard laboratory techniques (serum protein electrophoresis, quantification of total immunoglobulins, serum immunofixation, serum free light chain [FLC] assay) and HLC assay. HLC ratios outside the normal range were found in 58 of 90 patients, including 28 out of 61 patients with total immunoglobulin measurements within the normal range and 5 out of 23 patients in complete response. Both elevated HLC isotype level and abnormal HLC ratio correlated with the parameters of tumor burden, including percentage of plasma cells in the bone marrow (P<0.001 and P=0.002, respectively) ...
Conventional diagnostics in multiple myeloma
European Journal of Cancer, 2006
This paper reviews the most relevant laboratory techniques currently used for the evaluation of patients with multiple myeloma (MM) and other monoclonal gammopathies. Although the bone marrow morphological examination and electrophoretic analysis of the monoclonal paraprotein still remain the 'gold standard' techniques for fast, accurate and cost-effective diagnosis, other assays such as immunophenotyping, DNA cell content and cell cycle analysis measured by flow cytometry may contribute to a better assessment of myeloma patients. Here, we will discuss not only the contribution of each technique to differential diagnosis of monoclonal gammopathies, but also the value of each parameter as prognostic factor and for monitoring treatment efficacy. In addition, possible technical pitfalls inherent to each technique will be analysed.
American Journal of Hematology
The International Myeloma Working Group (IMWG) guidelines recommend using electrophoresis and immunofixation to define response and progressive disease (PD) in immunoglobulin (Ig) secretory multiple myeloma (Ig‐MM), whereas the role of serum‐free light chain (sFLC) is controversial. We retrospectively analyzed the value of adding sFLC assays in the definition of response and PD according to IMWG criteria in 339 Ig‐MM patients treated with a first‐line novel agent‐based therapy (median follow‐up 54 months). sFLC PD was defined according to conventional criteria plus increased sFLC levels, or sFLC escape (sFLCe); progression/sFLCe‐free survival (ePFS) was the time from the start of treatment to the date of first PD or sFLCe, or death; overall survival after PD/sFLCe (OS after Pe) was the time from first PD or sFLCe to the date of death. 148 (44%) patients achieved a complete response and 198 (60%) a normal sFLC ratio (sFLCR). sFLCR normalization was an independent prognostic factor fo...
Monitoring IgA Multiple Myeloma: Immunoglobulin Heavy/Light Chain Assays
Clinical Chemistry, 2014
BACKGROUND The use of electrophoresis to monitor monoclonal immunoglobulins migrating in the β fraction may be difficult because of their comigration with transferrin and complement proteins. METHODS Immunoassays specific for IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ heavy/light chain (HLC) were validated for use in the clinical laboratory. We assessed sample stability, inter- and intraassay variability, linearity, accuracy, and reference intervals for all 6 assays. We tested accuracy by verifying that the sum of the concentrations for the HLC-pairs accounted for the total immunoglobulins in each of 129 healthy sera, and that the HLC-pair ratios (rHLCs) were outside the reference interval in 97% of 518 diagnostic multiple myeloma (MM) samples. RESULTS We assessed diagnostic samples and posttreatment sera in 32 IgG and 30 IgA patients for HLC concentrations, rHLC, and total immunoglobulins and compared these nephelometry results with serum protein electrophoresis (SPEP) and immunofixati...
Journal of Clinical Oncology, 2011
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 ...
Cancers, 2021
Background: In the era of novel drugs a growing number of multiple myeloma (MM) patients are treated until disease progression. Serum free light chain (sFLC) assay is recommended for disease monitoring in oligo-secretory and micromolecular MM. Methods: In this real-life survey, a total of 130 relapsed/refractory MM patients treated at our center with at least three lines were investigated as a retrospective cohort. Results: The median age at diagnosis was 64 years and more than half of patients were male. A total of 24 patients (18%) had oligo-secretory/micromolecular disease at diagnosis. More than 20% of 106 normo-secretory patients had oligo-secretory/micromolecular escape. In order to evaluate potential role of sFLC assay before (“pre”) and after (“post”) every treatment line, involved serum free light chain values (iFLC) less than 138 mg/mL and serum free light chain ratios (FLCr) <25 were identified by using ROC curve analysis. The analysis of the entire cohort throughout f...
Blood, 2010
complete remission in multiple myeloma patients Questionable role of free light chain assay ratio to determine stringent http://bloodjournal.hematologylibrary.org/content/115/16/3413.full.html Updated information and services can be found at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub\_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009;23(2):215-224. 5. Mö sbauer U, Ayuk F, Schieder H, et al. Monitoring serum free light chains in patients with multiple myeloma who achieved negative immunofixation after allogeneic stem cell transplantation. Haematologica. 2007;92(2):275-276. 6. Blade J, Samson D, Reece D, et al. Criteria for evaluation disease response and progrssion in patients with multiple myeloma treated by high-dose therapy and hematopoietic stem cell transplantation.
British Journal of Haematology, 2003
The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is ‡ 30 g/l and/or bone marrow clonal cells ‡ 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (± recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.