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 assessment 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 nivolumab. 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 electrophoresis (IFE) as two IgG-kappa bands that migrate close to each other at the cathodal end of the γ-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 simultaneous quantitative monitoring of both the M-protein and t-mAbs.
|Number of pages||9|
|Journal||Clinical Chemistry and Laboratory Medicine|
|Early online date||16 Aug 2021|
|Publication status||Published - 1 Nov 2021|
Bibliographical noteFunding Information:
Competing interests: NvdD received research support from Janssen Pharmaceutical, Amgen, Celgene, Novartis, Cellectis, and Bristol-Myers Squibb; Advisory boards for Janssen Pharmaceuticals, Amgen, Celgene, Bristol-Myers Squibb, Novartis, Roche, Takeda, GSK, Sanofi, Bayer and Servier. JFMJ received a Dutch Cancer Society Grant (#10817) and research support from Sebia. The other authors state no conflict of interest.
Research funding: NvdD received research support from Janssen Pharmaceutical, Amgen, Celgene, Novartis, Cellectis, and Bristol-Myers Squibb. JFMJ received a Dutch Cancer Society Grant (#10817) and research support from Sebia. The other authors have nothing to disclose.
© 2021 Somayya Noori et al., published by De Gruyter, Berlin/Boston.