Monitoring minimal residual disease in patients with multiple myeloma by targeted tracking serum M-protein using mass spectrometry (EasyM)

Abstract Purpose: We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma (MM). Patients and Methods: 447 sequential serum samples from 56 MM patients were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic sample; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10-5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated. Results: Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive , sensitivity was 99.6% vs. IFE and 100.0% vs. MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), while specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for PFS (HR: 3.15 [1.26, 7.86]), the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR: 0.25 [0.12, 0.52]) and OS (HR: 0.16 [0.06, 0.40]). Conclusions: EasyM is a highly sensitive and minimal invasive method of MRD monitoring in MM, MS-MRD had significant predictive ability for survival outcomes.