Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
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Niels W.C.J. van de Donk
Abstract
Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). In this clinical case study we demonstrate that daratumumab can be detected as an individual monoclonal band in serum immunofixation electrophoresis (IFE). M-protein follow-up by IFE is part of the International Myeloma Working Group (IMWG) criteria to assess treatment response. Therefore, it is crucial that the daratumumab band is not confused with the endogenous M-protein of the patient during IFE interpretation. Moreover, a significant number of IgG-κ M-proteins co-migrate with daratumumab. Co-migration introduces a bias in the M-protein quantification since pharmacokinetic studies show that daratumumab peak plasma concentrations reach up to 1 g/L. More importantly, co-migration can mask clearance of the M-protein by IFE which is necessary for classification of complete response by IMWG criteria (negative serum IFE). For optimal M-protein monitoring the laboratory specialist needs to be informed when patients receive daratumumab, and it is essential that the laboratory specialist is aware that a slow migrating band in the γ-region in those patients may be derived from the daratumumab. A daratumumab specific IFE reflex assay (DIRA) has been developed and can be utilized to abrogate interference. The here described mAb interference is not limited to daratumumab, and as therapeutic antibodies gain approval and enter into common clinical practice, laboratory specialists will need additional processes to characterize IFE interference and distinguish endogenous M-protein from therapeutic antibodies.
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©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Editorial
- Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
- Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
- Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
- Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
- Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
- The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
- Serum and Urine Protein Electrophoresis and Immunofixation Testing
- Challenges of measuring monoclonal proteins in serum
- Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
- Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
- Moving towards harmonized reporting of serum and urine protein electrophoresis
- Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
- Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
- New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
- Serum Free Light Chain Methods and Controversies
- Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
- Measurement of free light chains with assays based on monoclonal antibodies
- Measurement of free light chains – pros and cons of current methods
- Is accuracy of serum free light chain measurement achievable?
- Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
- A patient with AL amyloidosis with negative free light chain results
- Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
- Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
- New Laboratory Assays and Challenges
- Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
- Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
- Free light chains and heavy/light chains in monitoring POEMS patients
- Monitoring free light chains in serum using mass spectrometry
- Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
- Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
- Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
- Letter to the Editor
- Discrepancy between FLC assays: only a problem of quantification?
Articles in the same Issue
- Frontmatter
- Editorial
- Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
- Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
- Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
- Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
- Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
- The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
- Serum and Urine Protein Electrophoresis and Immunofixation Testing
- Challenges of measuring monoclonal proteins in serum
- Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
- Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
- Moving towards harmonized reporting of serum and urine protein electrophoresis
- Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
- Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
- New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
- Serum Free Light Chain Methods and Controversies
- Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
- Measurement of free light chains with assays based on monoclonal antibodies
- Measurement of free light chains – pros and cons of current methods
- Is accuracy of serum free light chain measurement achievable?
- Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
- A patient with AL amyloidosis with negative free light chain results
- Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
- Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
- New Laboratory Assays and Challenges
- Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
- Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
- Free light chains and heavy/light chains in monitoring POEMS patients
- Monitoring free light chains in serum using mass spectrometry
- Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
- Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
- Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
- Letter to the Editor
- Discrepancy between FLC assays: only a problem of quantification?
