Monitoring the M-protein of multiple myeloma patients treated with a combination of monoclonal antibodies: The laboratory solution to eliminate interference

Somayya Noori, Christie P. M. Verkleij, Marina Zajec, Pieter Langerhorst, Patricia W. C. Bosman, Yolanda B. de Rijke, Sonja Zweegman, Martijn Vanduijn, Theo Luider, Niels W. C. J. van de Donk, Joannes F. M. Jacobs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1963-1971
Number of pages9
JournalClinical Chemistry and Laboratory Medicine
Issue number12
Early online date2021
Publication statusPublished - 1 Nov 2021

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