MRD and Biomarkers

The utility of mass spectrometry in defining minimal residual disease in treated multiple myeloma patients

P-184: The utility of mass spectrometry in defining minimal residual disease in treated multiple myeloma patients

Thursday, September 26, 2024

Karthik Ramasamy, MBBS FRCP FRCPath PhD

Associate Professor of Haematology & Consultant Haematologist
Department of Haematology, Oxford University Hospitals NHS Foundation Trust / Radcliffe Department of Medicine, University of Oxford, Oxford, Oxfordshire, UK, United Kingdom

Introduction: In multiple myeloma (MM), minimal residual disease (MRD) negativity following therapy correlates with longer progression-free survival (PFS). The FDA has recently approved the use of MRD in complete response (MRD in CR) as an accelerated approval endpoint in MM trials. Compared with gold standard bone marrow (BM) MRD techniques, a minimally invasive blood-based MRD test would be ideal due to ease of collection and ability to take longitudinal measurements. Mass spectrometry (MS) techniques provide a highly sensitive method to detect and monitor patient specific M-proteins. This study aimed to compare the sensitivity and prognostic utility of MS with BM next generation flow cytometry (NGF) at MRD time points and with IMWG CR criteria at best response and MRD timepoints within a UK hospital setting.

Methods: MS analysis was performed within a UK hospital laboratory using a MALDI-TOF MS system (EXENT, The Binding Site, UK). Transplant eligible and non-transplant eligible patients were recruited at varying stages of disease. Median follow up was 18 months. A total of 240 serum samples from 137 individual patients were tested for the presence of M-protein by conventional methods (serum electrophoresis (SPEP), immunofixation (IFE), free light chain (FLC)) and MS. BM NGF was performed to a sensitivity between 10 ^-5 and 10^-6 at pre- and 100 days post-transplant for a subset of patients.

Results: When compared to conventional techniques MS showed increased sensitivity over an algorithm of SPEP, IFE and FLC. Comparing MS against NGF results, agreement at pre-transplant was 88%. At post-transplant agreement was 56%, with 4 NGF negative samples being MS negative and 4 NGF negative samples being MS positive.

Evaluating PFS at post-transplant showed that a negative NGF MRD status approached significance (p=0.051). At this same time point the IMWG response status (CR vs non-CR) did not have a significant association with PFS (p=0.44). However, MS positivity post-transplant was significantly associated with an inferior PFS outcome (p=0.02).

When evaluating patients at best response, 80% of samples classified as CR were MS positive. Across all response groups MS negativity showed a significant PFS advantage and this was also seen when analysing those in CR only (p=0.002). This suggests that MS can be used to define deeper response groups, including refinement of “MRD in CR”.

Conclusions: This study aimed to evaluate the viability of using MS to identify M-proteins and define MRD in treated MM patients in a hospital laboratory setting. We found MS outcompeted the algorithm of SPEP/IFE/FLC in detecting the presence of M-protein. Our data suggest that MS negativity carried comparable prognostic performance to BM MRD negativity at the 10^-5to 10^-6 threshold. We propose that MS is a powerful MRD tool that can be complementary to BM MRD techniques and be used to guide BM sampling. The use of a blood-based assay will improve the patient experience of MRD testing.