B-371 Two Cases of Multiple Myeloma Achieving Complete Remission But Presenting Residual M-protein by the EXENT® Solution
Authors: Berlanga O , Birtwistle J , Allen S , Malin G , Lakos G 
Published: September 2023

Abstract

Background
Disappearance of the monoclonal component is a condition for achieving complete response (CR), which requires confirmation by bone marrow biopsy for the absence of clonal plasma cells. Electrophoretic methods used for monitoring these patients lack sufficient sensitivity to identify low-level M-protein, potentially missing the presence of serological residual disease once the tests become negative. The EXENT® solution (in development by The Binding Site, part of Thermo Fisher scientific) uses matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for the identification and quantification of M-proteins. The technique offers high sensitivity and specificity for identifying and tracking M-proteins. The aim of this study is to determine whether the superior analytical sensitivity of mass spectrometry conveys any clinical benefit to patient monitoring.

Methods
We present two multiple myeloma patients seen during routine practice. Baseline and longitudinal samples were available. Serum samples were retrospectively analysed with the EXENT® solution. Briefly, diluted samples were separately incubated with antisera specific for IgG, IgA, IgM, total-κ and total-λ conjugated to paramagnetic beads. Purified immunoglobulins were reduced and eluted from the beads, the solution mixed with matrix, spotted onto MALDI plates, and acquired by MALDI-TOF-MS to determine mass-to-charge (m/z), isotype and concentration of the M-proteins. Results were compared to serum protein electrophoresis (SPE) and free light chains (FLC; Freelite, The Binding Site). The EXENT solution responses were modelled on those from the International Myeloma Working Group. CR by MS refers to absence of the original monoclonal peak during follow-up.

Results
Case 1 is a 68-year-old white male presenting with 11.7 g/L monoclonal IgGκ on SPE and abnormal FLC ratio (3.06). After initiating therapy, FLC ratio normalized at month 2, whereas SPE became negative at month 8, at which time a CR was confirmed. The patient stayed in remission for over two-and-a-half years before relapsing at month 40, as determined by re-appearance of the M-protein on SPE (2.20 g/L). The EXENT solution also identified an IgGκ peak at baseline (m/z = 11629, 11.9 g/L). The peak remained present until month 19, disappeared for over a year, then reemerged at month 36 (0.39 g/L) to indicate progression. Thus, the EXENT solution identified the presence of residual M-protein (&lt;1 g/L) for an additional eleven months after standard monitoring methods indicated CR; and recognized relapse from CR four months before SPE.Case 2 is a 76-year-old Asian male presenting with 32.9 g/L monoclonal IgGλ on SPE and normal FLC ratio (0.43). The EXENT solution reported an IgGλ peak (m/z = 11250, 44.3 g/L) at this time. SPE became negative ten months after starting treatment; and identified relapse from CR one year after. The EXENT solution remained positive throughout and was the only method detecting low-level M-protein (≤1.25 g/L) during the 1-year remission period.

Conclusion
EXENT demonstrates a potentially superior performance over electrophoretic methods for identifying residual serological disease during monitoring; and shows potential as a serum biomarker of early relapse in myeloma. The improved sensitivity of MS suggests it may delay and, in some cases, avoid the need for invasive methods to determine response to therapy.