Abstract
We assessed the ability of a mass spectrometry-based technique, called monoclonal immunoglobulin rapid accurate mass measurement (miRAMM), to extend the analytical range of M-protein detection in serum samples obtained from myeloma patients in stringent complete response (sCR) post-autologous stem cell transplant (ASCT). To aid the M-protein detection post ASCT, the accurate molecular mass of the M-protein light chain at diagnosis was determined in all patients (N=30) and used to positively identify clones in the sCR serum. Day 100 post-ASCT, sCR samples had miRAMM identifiable M-proteins in 81% of patients. Patients who had achieved only a partial remission (PR) pre-ASCT and those with IgG isotypes serum samples had the highest rate of M-protein detection by miRAMM. miRAMM positivity at single time points (day 100, 6 months or 12 months) did not correlate with progression-free survival (PFS). In contrast, sCR patients who did not decrease their miRAMM M-protein intensities in serial measurements had shorter PFS than those whose miRAMM intensities decreased (median 17.9 months vs 51.6 months; P<0.0017). miRAMM M-protein is a more sensitive blood-based test than traditional M-protein tests and could cost effectively aid in serially monitoring complete remission for continue response or biochemical relapse.
Highlights
As the number of effective therapies for treatment of multiple myeloma continues to increase, a greater proportion of patients are achieving deep therapeutic responses.[1,2,3] Traditionally, serum and urine M-protein measurements by immunoelectrophoresis were sufficient to define treatment responses in 90% of cases.[4]
The use of a high-resolution mass spectrometric (MS) capable of achieving a mass measurement accuracy (o 15 p.p.m.) enabled the distinction of any liquid chromatography (LC) with at least a 1 Da difference in mass. This mass accuracy was essential for evaluating post-autologous stem cell transplant (ASCT) serum samples as it was common for these samples to contain several ‘M-spikes’ in the LC mass distribution (Figure 1)
To establish an M-spike in a post-ASCT sample as related to the original M-protein, the LC mass had to match the original peak within ± 1 Da and the LC retention time within ± 30 s of the diagnostic sample
Summary
As the number of effective therapies for treatment of multiple myeloma continues to increase, a greater proportion of patients are achieving deep therapeutic responses.[1,2,3] Traditionally, serum and urine M-protein measurements by immunoelectrophoresis were sufficient to define treatment responses in 90% of cases.[4]. (TOF)-based MS platforms has been adapted to a lower cost chromatography-free matrix assisted laser desorption/ionization Liquid chromatography (MALDI)-TOF MS platform with performance properties suited for the high volume clinical lab.[16] Analytical times are rapid (o 1 minute per patient) and when combined with five separate immunoprecipitations for IgG, IgA, IgM, κ and λ,the method can detect, quantitate and isotype M-proteins.
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