In collaboration with Rapid Novor and University of Waterloo, the Trudel group at Princess Margaret Cancer Centre in Toronto have developed a non-invasive MS-based test to assess minimal residual disease (MRD), a measure of depth of remission to treatment, which has become an important parameter in assessing the disease burden in multiple myeloma.
M-protein is a well-established biomarker used for multiple myeloma (MM). Following treatment, it is important to monitor levels of the M-protein, which currently require painful bone marrow aspiration preventing frequent sampling. The authors present a non-invasive assay, called EasyM, where residual levels of M-protein can be measured from serum by mass spectrometry and thus can be performed frequently to monitor the disease status in complete remission patients and predict the relapse early.
The EasyM assay is a personalized blood-based test consisting of two steps. In the first step, the diagnostic serum sample is digested with multiple proteases and measured with the 30 samples per day method on the Evosep One to determine the full sequence of the M-protein. Unique tryptic peptides are then selected for each patient. In the second step, diagnostic as well as follow-up serum samples are digested with trypsin and analyzed with a PRM assay with the 60 samples per day method to quantify the amount of M-protein at the subsequent time points relative to the diagnostic sample. The reported value of percent residual M-protein can then be used to assess the disease status, monitor response to treatment, or predict disease relapse.
The study analyzed serial serum samples of 26 MM patients enrolled in the Myeloma Canada Research Network (MCRN)-001 study of augmented conditioning with busulfan and melphalan followed by lenalidomide maintenance. Based on these samples, they established the M-protein LLoQ and LOD for the 2-3 best quantotypic peptides for each patient resulting in use of the peptide with the lowest LLoQ for M-protein monitoring.
They monitored the M-protein from diagnosis through treatment and relapse from serum samples analyzed with the patient-specific PRM assay. The high sensitivity of the EasyM assay allowed them to detect and quantify M-protein even when quantification was not possible with conventional assays, thus allowing for early and accurate detecting of relapse.
In conclusion, they have developed and validated a non-invasive, sensitive, personalized assay that is ideal for frequent monitoring of multiple myeloma patients in complete remission. They hope to further develop their assay, allowing to sequence more than one M-protein and improve the sensitivity even further.
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This publication by the Trudel group describes the development of a non-invasive MS-based assay, called EasyM, which is used to assess minimal residual disease, a measure of depth of response to treatment, which has become an important parameter in assessing the disease burden in multiple myeloma.
The amino acid sequence of the M-protein for multiple myeloma is unique compared to the polyclonal antibodies in patients’ blood. This publication from Rapid Novor describes a targeted MS/MS assay to detect and quantify the unique M-protein sequence in serum samples from multiple myeloma patients.
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