High sensitivity blood-based M-protein detection in sCR patients with multiple myeloma

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.

Figure 1

A deepening miRAMM response is suggestive of longer PFS in patients in sCR. Examples of miRAMM data. The top panel indicates a patient who had a miRAMM relapsed. At diagnosis the monoclonal LC mass signature was readily identifiable (red arrow). This mass signature was then assessed in subsequent post-treatment samples. At day 100, there is undetectable disease by miRAMM (dashed red arrow). The astrisk indicates a secondary oligoclonal response. However, ~200 days later there MS signature of this patients disease had re-emerged indicating a relapse (red arrow). The bottom panel indicates a patient with a deepening miRAMM response. Between diagnosis and 100 days post-ASCT, the MS signature for this patient decreased from an intensity of 160 000 to 40 000. Approximately 200 days later, this has continued to decline and is now at 4500.