Mass spectrometry as a tool for minimal residual disease detection in the blood of myeloma patients

M-protein detection and quantification are integral parts of the diagnosis and monitoring of multiple myeloma. Novel treatment modalities impose new challenges on the traditional electrophoretic and immunochemical methods that are routinely used for M-protein diagnostics, most importantly the need for increased sensitivity to measure minimal residual disease (MRD). In the past two decades flow cytometric and next generation sequencing methods have been developed to assess MRD in bone marrow aspirates of patients with multiple myeloma. MRD-status is an important independent prognostic marker and its potential as surrogate endpoint for progression-free survival is currently studied. In addition to that, numerous clinical trials are investigating the added clinical value of MRD-guided therapy decisions in individual patients. Because of these novel clinical applications, repeated MRD-evaluation is becoming common practice, also in regular management of patients outside clinical trials. A disadvantage of MRD-evaluation on bone marrow aspirates is the risk of sampling-error, resulting from heterogenous dispersion of myeloma cells and/or extramedullary myeloma outgrowth. In addition, invasive bone marrow biopsies are a burden to patients. Recently, advances have been made in ultra-sensitive detection and quantitation of serum M-proteins using mass spectrometry (MS-MRD), which represents an attractive minimally invasive alternative to bone marrow-based MRD-evaluation. Several studies have shown that MS-MRD blood-testing is feasible in all patients with multiple myeloma and that it has similar sensitivity and prognostic value compared to NGS-MRD evaluation performed on bone marrow. The MS-MRD blood-test paves the way for dynamic MRD monitoring to allow detection of early disease relapse (see Figure) and may proof to be a crucial factor to facilitate future clinical implementation of MRD-guided therapy.Figure.: Early relapse detection with dynamic MS-MRD monitoring.MS-MRD blood monitoring on 26 sera of one patient with multiple myeloma treated in the IFM2009 clinical trial. The increased sensitivity of MS-MRD (black) compared to routine M-protein diagnostics (blue) allows early detection of disease relapse.