(PA-200) Performance and Additional Benefits of Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry in M-Protein Detection in Plasma Cell Disorders

Current recommendations for detecting monoclonal immunoglobulin component (M-proteins) include immunofixation electrophoresis (IFE) and serum protein electrophoresis (SPEP). However, these methods have been progressively limited in clinical application due to low sensitivity and time-consuming operation. The aim of this study was to examine the feasibility of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) to qualitatively detect M-proteins. 

Methods:

Peripheral blood samples from 137 newly diagnosed patients with plasma cell disorders (PCDs) were collected for MALDI-TOF-MS analysis. The performance of MALDI-TOF-MS in identifying M-proteins using serum and plasma samples was evaluated with the results of SPEP and IFE as the reference standard.

Results:

Our cohort included 105 MM (89.0%), 13 AL amyloidosis (11.0%), 4 MGUS (2.9%), 3 plasmacytoma (2.5%), 1 POEMS syndrome (0.7%). With SPEP/IFE results as the gold standard, serum-based MALDI-TOF-MS had 96.4% (132/137) agreement in determining the M-proteins, with specificity of 98.5% (132/134). With clinical results as a reference, MALDI-TOF-MS achieved higher accuracy than SPEP/IFE in identifying M proteins (99.3% vs. 97.1%). Meanwhile, detection of M-proteins using plasma samples yielded a concordance of 88.3% (121/137) with SPEP/IFE results as reference. Moreover, MALDI-TOF-MS offered additional benefits, including the identification of light chain (LC) glycosylation in 17 patients and other aberrant peaks associated with post-translational modifications (PTMs) in 4 patients. Interestingly, by monitoring post-treatment changes in M-proteins in some patients via MALDI-TOF-MS, we found that 2 patients who achieved elimination of the glycosylation peak after treatment exhibited complete response, whereas 1 patient with persistent glycosylation peak showed very good partial response.

Conclusions:

MALDI-TOF-MS is a dependable substitute for SPEP/IFE, delivering superior diagnostic and efficacy prediction values by characterizing LC glycosylation and uncovering PTM-associated spectral peaks. Our study provides robust evidence supporting the feasibility of MALDI-TOF-MS for widespread clinical application in the M-protein detection.