M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass-spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab, and nivolumab). This assay can target proteotypic M-protein peptides as well as unique peptides derived from therapeutic monoclonal antibodies. We address the sensitivity in M-protein diagnostics and show that our mass-spectrometry assay is more than two orders of magnitude more sensitive than conventional M-protein diagnostics. The use of stable isotope-labeled peptides allows absolute quantification of the M-protein and increases the potential of assay standardization across multiple laboratories. Finally, we discuss the position of mass-spectrometry assays in monitoring minimal residual disease in multiple myeloma, which is currently dominated by molecular techniques based on plasma cell assessment that requires invasive bone marrow aspirations or biopsies.

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Keywords daratumumab, ipilimumab, M-protein, multiple myeloma, nivolumab, response assessment, targeted mass-spectrometry, therapeutic monoclonal antibody
Persistent URL dx.doi.org/10.1021/acs.jproteome.7b00890, hdl.handle.net/1765/105076
Journal Journal of Proteome Research
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Zajec, M, Jacobs, J.F.M. (Joannes F. M.), Groenen, P.J.T.A, De Kat Angelino, C.M. (Corrie M.), Stingl, C, Luider, T.M, … van Duijn, M.M. (2018). Development of a Targeted Mass-Spectrometry Serum Assay to Quantify M-Protein in the Presence of Therapeutic Monoclonal Antibodies. Journal of Proteome Research, 17(3), 1326–1333. doi:10.1021/acs.jproteome.7b00890