MALDI-TOF mass spectrometry distinguishes daratumumab from M-proteins

• Published in: Clinica chimica acta Vol. 492; pp. 91 - 94
• Main Authors: Moore, Lauren M., Cho, Sun, Thoren, Katie L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-05-2019
• Subjects: Antibodies, Monoclonal - blood; Daratumumab; False Positive Reactions; Humans; MALDI-TOF mass spectrometry; Monoclonal immunoglobulin; Multiple myeloma; Myeloma Proteins - analysis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; MALDI-TOF MS; FDA; Daratumumab; MSKCC; Multiple myeloma; MALDI-TOF mass spectrometry; IFE; M-protein; Monoclonal immunoglobulin; SPEP; mAb
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2019.02.017

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).
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.
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.
MALDI-TOF MS offers greater specificity compared to immunofixation for distinguishing daratumumab from M-proteins.
•The mass of light chains can be used to distinguish daratumumab from M-proteins.•Mass spectrometry is more specific than immunofixation for this purpose.•The analytical specificity will depend on the mass resolution of the instrument.