Distinguishing Daratumumab from Endogenous Monoclonal Proteins in Serum from Multiple Myeloma Patients Using an Automated Mass Spectrometry System.

Abstract

Background: Therapeutic monoclonal antibodies (t-mAbs) may interfere with electrophoresis-based methods used to monitor multiple myeloma (MM), which can create inaccurate results. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is an alternative to gels distinguishing between endogenous M-proteins and t-mAbs based on molecular mass.

Methods: Serum samples (n = 109) from 34 MM patients receiving Dara-KRd were collected 14 or 28 days postdaratumumab administration. Samples were analyzed using the EXENT® Analyzer that combines automated immunopurification and MALDI-TOF MS for the isotyping and quantification of monoclonal immunoglobulins.

Results: Daratumumab was identified in 103 out of 109 samples (94.5%). In all IgGλ (n = 8), IgAκ (n = 8), and IgAλ (n = 2) patients, the M-protein and daratumumab were detected. Of the IgGκ patients (n = 18), 5 patients had a total of 6 samples where the M-protein was detected but daratumumab was not. There was no difference in the detection rate of daratumumab between samples taken 14 and 28 days postadministration with the median daratumumab concentration being 0.95 and 0.54 g/L, respectively. A precision study was also performed on 25 replicates containing 1 g/L daratumumab in serum where a coefficient of variation of 4.2% was observed as determined by the EXENT Analyzer.

Conclusions: The Immunoglobulin Isotypes (GAM: IgG, IgA, and IgM) for the EXENT Analyzer detected and distinguished a daratumumab kappa light chain peak from an M-protein light chain peak in MM patient serum when resolved by the mass spectrometer.