Performance and additional benefits of MALDI-TOF-MS in M-protein detection in plasma cell disorders

PURPOSES: Current methods for detecting monoclonal (M) proteins, such as immunofixation electrophoresis (IFE), serum protein electrophoresis (SPEP) and serum free light chains (sFLC), are limited by insufficient sensitivity and suboptimal efficiency. This study evaluated the performance and supplementary value of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) for the detection of M-protein. METHODS: The M protein in the blood samples of 137 newly diagnosed plasma cell disorder (PCD) patients were detected using MALDI-TOF-MS. Using SPEP/IFE/sFLC as the gold standard, the performance of MALDI‑TOF MS was assessed; discrepant results were confirmed by urine IFE. RESULTS: The cohort included multiple PCD subtypes, detailly, 116 multiple myeloma (MM, 84.7%), 7 amyloid light-chain (AL) amyloidosis (5.1%), 6 MM combined with AL amyloidosis (4.4%), 4 monoclonal gammopathy of undetermined significance (MGUS, 2.9%), and others. Serum-based MALDI-TOF-MS demonstrated a high detection rate for M-protein identification compared to SPEP, serum IFE, sFLC and urine IFE (98.5% vs. 75.9% vs. 86.9% vs. 71.5% vs. 76.0%). Plasma-based testing achieved a concordance rate of 89.1% (122/137). Using IFE/sFLC results as the gold standard, the sensitivity of MALDI-TOF-MS for the identification of κ and λ light chains (LC) was 75.8% and 80.0%, respectively. For IgG and IgA identification, the sensitivity of MALDI-TOF-MS was 93.5% (58/62) and 65.5% (19/29), respectively. Additionally, MALDI-TOF-MS detected LC glycosylation in 17 patients and other post-translational modifications (PTMs) in 4 patients. Notably, post-treatment monitoring revealed that two patients with eliminated glycosylation peaks achieved complete response, while one with persistent glycosylation had a very good partial response. CONCLUSIONS: MALDI-TOF-MS is a reliable tool for M-protein detection, offering high detection rate, LC glycosylation identification, and PTM analysis. Additionally, in a small cohort, we observed that changes in the abnormal peaks detected by MALDI-TOF-MS may correlate with treatment response.