posted on 2018-02-09, 00:00authored byMarina Zajec, Joannes F. M. Jacobs, Patricia J. T.
A. Groenen, Corrie M. de Kat Angelino, Christoph Stingl, Theo M. Luider, Yolanda B. De Rijke, Martijn M. VanDuijn
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.