ASCO 2021 | GEM2012MENOS65: treatment response assessment by mass spectrometry

A summary of the abstract that the organizers of the EHA have selected for a presentation and that we have entitled, “Serum protein electrophoresis and immunofixation vs mass spectrometry for response assessment in newly diagnosed multiple myeloma patients from the GEM2012MENOS65 clinical trial.”

Various studies have shown that mass spectrometry could be a more sensitive method as compared to protein electrophoresis and immunofixation for detecting the M-protein as a biomarker in serum samples from patients with myeloma. So, the aim of this study was to compare mass spectrometry against the standard techniques, that is with serum protein electrophoresis and mainly immunofixation, for the detection of the monoclonal component in multiple myeloma patients enrolled in the PETHEMA GEM2012MENOS65 trial.

So, we included the first 186 out of the 458 newly diagnosed multiple myeloma patients enrolled in this trial. The presence of the, the presence of the M-protein in serum was evaluated in parallel by immunofixation and by mass spectrometry, using IgG/A/M, kappa, lambda, free kappa, and free lambda isotypic specific beats, and both tests were carried out after induction at day 100 post-transplant, and after consolidation.

So first, we analyzed the percentage of cases with a detectable monoclonal component with serum protein electrophoresis and immunofixation and by mass spectrometry. And so, serum protein electrophoresis and immunofixation, that is the conventional methods, identified the presence of an M-protein in 52% of cases post-induction, 36% post-transplant, and 27 post-consolidation, and in contrast, mass spectrometry did so in 63% of patients post-induction, 46 post-transplant, and 35 post-consolidation.

So then, we analyzed the results of the analysis of pair results of both methods. So, the percentage of concordances was around 85% at the three time points analyzed, and most these concordances were due to samples positive by mass spectrometry and negative by immunofixation, representing 14% of cases, post-induction, 12 post-transplant, and 12 post-consolidation. And in five cases post-induction, four post-transplant, and seven post-consolidation, the monoclonal component was exclusively detected by immunofixation.

Once confirmed the high-reliability of mass spectrometry to detect the M-protein as compared to standard methods, we compared their respective clinical value in terms of progression-free survival at the end of the treatment, that is post-consolidation.

So, whereas there were not statistically significant differences in the progression-free survival of positive and negative patients by serum protein electrophoresis and immunofixation, the progression-free survival of those patients in whom a monoclonal component could be detected by mass spectrometry was significantly lower as compared to those in whom a monoclonal component could not be identified.

So, when we investigated in 127 patients achieving CR post-consolidation, we found out that mass spectrometry was able to identify the presence of a monoclonal component in 21 of them. And further, the identification of the monoclonal component by mass spectrometry in this group of patients in a standard CR, that is with immunofixation-negative, was associated with a significantly shorter progression-free survival.

So, in conclusion, as compared to a standard methods to detect the monoclonal component in serum, in this study, mass spectrometry identified the presence of the paraprotein in a higher proportion of patients throughout monitoring, was able to discriminate two groups of patients with different progression-free survival at treatment completion, and identified residual disease in a cohort of patients in a standard CR, but at increased risk of progression.