Mass Spectrometry Provides a Highly Sensitive Noninvasive Means of Sequencing and Tracking M-Protein in the Blood of Multiple Myeloma Patients

Zac McDonald, Paul Taylor, Mariya Liyasova, Qixin Liu, Bin Ma

DOI: 10.1021/acs.jproteome.0c01022

Publication Summary

The amino acid sequence of the M-protein for multiple myeloma is unique compared to the polyclonal antibodies in patients’ blood. This uniqueness is exploited to develop an ultrasensitive M-protein detection method utilizing mass spectrometry (MS).

This study demonstrates the effectiveness of EasyM in serially monitoring M-protein levels from the serum of a single MM patient, presented as a retrospective analysis, from diagnosis through complete remission (CR) and up to clinical relapse. Here, we provide a technical delineation of M-protein sequencing and quantitation using EasyM, a novel and highly sensitive, clonotypic peptides mass spectrometry-based minimal residual disease (MRD) assay that can be performed noninvasively in patient blood samples.

Key takeaways:

• Demonstration of the high sensitivity and specificity of the clonotypic peptides approach to monitoring M-protein levels using mass spectrometry in serum
• EasyM was able to detect and track M-protein levels in all serial samples, most notably through CR when serum protein electrophoresis (SPEP) and immunofixation (IFE) were negative
• A 2-fold increase in M-protein levels could be detected 10 months prior to the point of relapse as detected by IFE

Tracking target M-protein in MM patient MM2232. Y-axis: Percent residual M-protein from baseline in log10 scale.

X-axis: Date of sample collection and clinical assessment of disease state.