Peripheral measurable residual multiple myeloma disease activity assessment by MALDI-TOF mass spectrometry

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM). Analysis of 3301 serum samples from 617 patients enrolled in the multicenter phase 3 GMMG-HD7 trial in Germany characterized the analytical performance and clinical relevance of MS-based measurable residual activity. MS reliably distinguished therapeutic antibodies, tracked diagnostic M proteins longitudinally, and demonstrated strong prognostic value across defined time points. MS negativity was associated with superior progression-free survival (PFS), with the greatest separation at later time points (12 months of maintenance: HR 0.25; p<0.001). Assessment by MS combined with bone-marrow measurable residual disease (MRD) further refined risk stratification: MS/MRD double-positive patients exhibited the worst PFS. MS-MRD concordance increased over time and was influenced by immunoglobulin isotype. MS provided accurate M-protein detection and outperformed serum protein electrophoresis at low concentrations, reliably quantifying low-level residual disease. The authors conclude that serum MS is a sensitive, reproducible, and practical biomarker that complements MRD and supports minimally invasive disease monitoring in MM.