Journal
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
Volume 59, Issue 12, Pages 1963-1971Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/cclm-2021-0399
Keywords
daratumumab; hydrashift; immunofixation electrophoresis; mass spectrometry; monoclonal antibody; M-protein; multiple myeloma; nivolumab; serum protein electrophoresis; therapeutic drug monitoring
Categories
Funding
- Janssen Pharmaceutical
- Amgen
- Celgene
- Novartis
- Cellectis
- Bristol-Myers Squibb
- Dutch Cancer Society Grant [10817]
- Sebia
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This study addresses the analytical challenges of monitoring M-protein when multiple therapeutic monoclonal antibodies (t-mAbs) are combined for treatment. The double hydrashift assay and MS-MRD assay were used to distinguish M-protein from t-mAbs and provide sensitive and quantitative monitoring.
Objectives: The therapeutic monoclonal antibody (t-mAb) daratumumab, used to treat multiple myeloma (MM) patients, interferes with routine, electrophoretic based M-protein diagnostics. Electrophoretic response assess-ment becomes increasingly difficult when multiple t-mAbs are combined for use in a single patient. This is the first study to address the analytical challenges of M-protein monitoring when multiple t-mAbs are combined. Methods: In this proof-of-principle study we evaluate two different methods to monitor M-protein responses in three MM patients, who receive both daratumumab and nivolu-mab. The double hydrashift assay aims to resolve t-mAb interference on immunofixation. The MS-MRD (mass spectrometry minimal residual disease) assay measures clonotypic peptides to quantitate both M-protein and t-mAb concentrations. Results: After exposure to daratumumab and nivolumab, both t-mAbs become visible on immunofixation electro-phoresis (IFE) as two IgG-kappa bands that migrate close to each other at the cathodal end of the gamma-region. In case the M-protein co-migrates with these t-mAbs, the observed interference was completely abolished with the double IFE hydrashift assay. In all three patients the MS-MRD assay was also able to distinguish the M-protein from the t-mAbs. Additional advantage of the MS-MRD assay is that this multiplex assay is more sensitive and allows quantitative M-protein-, daratumumab-and nivolumab-monitoring. Conclusions: Daratumumab and nivolumab interfere with electrophoretic M-protein diagnostics. However, the M-protein can be distinguished from both t-mAbs by use of a double hydrashift assay. The MS-MRD assay provides an alternative method that allows sensitive and simulta-neous quantitative monitoring of both the M-protein and t-mAbs.
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