Rapid identification and quantification of residual daratumumab in multiple myeloma patients by MALDI - TOF mass...

The introduction of anti-CD38 monoclonal antibodies, including daratumumab, has significantly improved response rates and survival outcomes in multiple myeloma (MM). However, these therapeutic monoclonal antibodies (t-mAbs) interfere with conventional electrophoretic techniques used for detecting and quantifying endogenous monoclonal proteins (M-proteins), posing challenges for treatment response assessment.

We systematically evaluated an enrichment-free, rapid MALDI-TOF mass spectrometry-based system (iMS-LC Assay) for its ability to differentiate daratumumab from M-proteins by analyzing serial serum samples from 38 multiple myeloma (MM) patients undergoing daratumumab treatment. Additionally, by spiking human serum with daratumumab, we established a reference m/z range and assessed the assay's analytical precision, limit of detection (LOD), and quantitative capabilities.

The iMS-LC Assay consistently identified daratumumab at a mean m/z of 23,384.63 (mean ± 3SD: 23,370-23,398), demonstrating high analytical precision (CV ≤ 2.8 %) and an LOD between 0.10 and 0.15 g/L. Daratumumab was detected in 90.55 % (182/201) of patient samples and distinguished from endogenous M-proteins in 94.74 % (36/38) of patients. It becomes challenging to distinguish t-mAbs from M-protein when the m/z of the M-protein is close to that of daratumumab and present at a high concentration.

The iMS-LC Assay facilitates specific, sensitive, and automated differentiation between daratumumab and M-proteins in most clinical settings, offering a practical alternative to traditional electrophoretic methods for monitoring treatment response in multiple myeloma patients undergoing anti-CD38 therapy.