MALDI-TOF mass spectrometry distinguishes daratumumab from M-proteins

Clin Chim Acta. 2019 May:492:91-94. doi: 10.1016/j.cca.2019.02.017. Epub 2019 Feb 18.

Abstract

Background: Daratumumab, a therapeutic IgG kappa monoclonal antibody, can cause a false positive interference on electrophoretic assays that are routinely used to monitor patients with monoclonal gammopathies. In this study, we evaluate the ability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to distinguish daratumumab from disease-related IgG kappa monoclonal proteins (M-protein).

Methods: Waste clinical samples from 31 patients who were receiving daratumumab and had a history of IgG kappa monoclonal gammopathy were collected. Immunoglobulins were purified from serum and analyzed by MALDI-TOF MS. Mass spectra were assessed for the presence of distinct monoclonal proteins. For samples in which only one monoclonal peak was identified near the expected m/z of daratumumab, the Hydrashift 2/4 Daratumumab Assay was used to confirm the presence of an M-protein.

Results: Using MALDI-TOF MS, daratumumab could be distinguished from M-proteins in 26 out of 31 samples (84%). Results from 2 samples were inconclusive since the M-protein was not detected by the Hydrashift assay and may also be undetectable by MALDI-TOF MS. Comparatively, daratumumab was distinguishable from M-proteins in 14 out of 31 samples (45%) by immunofixation.

Conclusions: MALDI-TOF MS offers greater specificity compared to immunofixation for distinguishing daratumumab from M-proteins.

Keywords: Daratumumab; MALDI-TOF mass spectrometry; Monoclonal immunoglobulin; Multiple myeloma.

MeSH terms

  • Antibodies, Monoclonal / blood*
  • False Positive Reactions
  • Humans
  • Myeloma Proteins / analysis*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*

Substances

  • Antibodies, Monoclonal
  • Myeloma Proteins
  • multiple myeloma M-proteins
  • daratumumab