M-protein diagnostics in multiple myeloma patients using ultra-sensitive targeted mass spectrometry and an off-the-shelf calibrator.
Clin Chem Lab Med
; 62(3): 540-550, 2024 Feb 26.
Article
in En
| MEDLINE
| ID: mdl-37823394
ABSTRACT
OBJECTIVES:
Minimal residual disease status in multiple myeloma is an important prognostic biomarker. Recently, personalized blood-based targeted mass spectrometry (MS-MRD) was shown to provide a sensitive and minimally invasive alternative to measure minimal residual disease. However, quantification of MS-MRD requires a unique calibrator for each patient. The use of patient-specific stable isotope labelled (SIL) peptides is relatively costly and time-consuming, thus hindering clinical implementation. Here, we introduce a simplification of MS-MRD by using an off-the-shelf calibrator.METHODS:
SILuMAB-based MS-MRD was performed by spiking a monoclonal stable isotope labeled IgG, SILuMAB-K1, in the patient serum. The abundance of both M-protein-specific peptides and SILuMAB-specific peptides were monitored by mass spectrometry. The relative ratio between M-protein peptides and SILuMAB peptides allowed for M-protein quantification. We assessed linearity, sensitivity and reproducibility of SILuMAB-based MS-MRD in longitudinally collected sera from the IFM-2009 clinical trial.RESULTS:
A linear dynamic range was achieved of over 5 log scales, allowing for M-protein quantification down to 0.001â¯g/L. The inter-assay CV of SILuMAB-based MS-MRD was on average 11â¯%. Excellent concordance between SIL- and SILuMAB-based MS-MRD was shown (R2>0.985). Additionally, signal intensity of spiked SILuMAB can be used for quality control purpose to assess system performance and incomplete SILuMAB digestion can be used as quality control for sample preparation.CONCLUSIONS:
Compared to SIL peptides, SILuMAB-based MS-MRD improves the reproducibility, turn-around-times and cost-efficacy of MS-MRD without diminishing its sensitivity and specificity. Furthermore, SILuMAB can be used as a MS-MRD quality control tool to monitor sample preparation efficacy and assay performance.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Multiple Myeloma
Type of study:
Clinical_trials
/
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Clin Chem Lab Med
Journal subject:
QUIMICA CLINICA
/
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Year:
2024
Document type:
Article
Affiliation country:
Países Bajos