Pb2139: monitoring oligosecretory multiple myeloma using maldi-tof mass spectrometry

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Up to 10% of newly diagnosed multiple myeloma (MM) patients present with oligosecretory disease. Due to the limited analytical sensitivity of serum protein electrophoresis (SPE) serum free light chain (FLC) measurements are recommended for monitoring these patients; provided FLC ratio is abnormal and involved FLC (iFLC) >100 mg/L at presentation. The EXENT® solution (in development by The Binding Site, part of Thermo Fisher scientific) uses matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry for the identification and quantification of M-proteins. Mass spectrometry has been previously shown to offer superior analytical sensitivity compared to SPE. Aims: The aim of this study was to assess the feasibility of mass spectrometry for monitoring oligosecretory disease. Methods: We identified 10 oligosecretory multiple myeloma patients (3 IgG kappa, 2 IgA kappa, 3 IgA lambda, 1 IgM kappa, 1 IgM lambda) in a cohort of monoclonal gammopathies. Median number of samples per patient was 9 (7-17), and median follow up was 18 (7-57) months. Serum samples were analyzed with the EXENT® solution, an automated MALDI-TOF mass spectrometry system that detects M proteins, determines their isotype and mass-to-charge (m/z) ratio, and provides concentration for IgG, IgA and IgM paraproteins. The results were compared to those by SPE. Responses were determined based on criteria from the International Myeloma Working Group. A complete response by the EXENT solution was defined as the absence of the monoclonal peak that was observed in the baseline sample, based on the same m/z value. Results: Median (range) of M-protein levels at baseline were 8.2 g/L (6.0-9.8) by SPE and 7.0 g/L (1.0-12.1) by the EXENT solution (p=0.21). In seven cases with available data iFLC levels were <100 mg/L, so none of the standard techniques were suitable for monitoring M-protein changes in these patients. From a total 90 monitoring time-points, SPE was negative in 24 samples, but the EXENT solution identified low-level M-protein in 20 of these (median [range]=0.5 [0.1-2.0] g/L). 4 patients achieved CR based on clinical assessment, and 1 by the EXENT solution; the latter was also negative by SPE. Among the 4 patients in standard CR, 2 subsequently relapsed; in these two patients, the results from the EXENT solution remained positive throughout. One of the patients in CR remained negative by SPE for two and a half years before relapsing, as determined by re-appearance of the M-protein. During this time the EXENT solution remained positive. The patient subsequently achieved a second CR but relapsed again after 8 months. As before, the EXENT solution identified residual disease during the CR period. Summary/Conclusion: The EXENT solution demonstrates the potential for the detection and quantification of low-level M-proteins and may be suitable for monitoring serological residual disease in oligosecretory MM patients. Further studies on larger cohorts and comparison with clinical assessment are necessary to validate the clinical utility of monitoring these patients with mass spectrometry. Keywords: Monoclonal gammopathy, Measurable residual disease