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.

Link: https://clincancerres.aacrjournals.org/content/clincanres/early/2021/07/01/1078-0432.CCR-21-0649.full.pdf

MORE RESEARCH ON targeted workflows

Here you can see publications available using targeted workflows featuring Evosep One. For a full overview of publications published using the Evosep One Technology visit our Literature room here

TitleSubjectMaterialYearSummaryEvosep methodMS instrumentationLearn More
A personalized mass spectrometry-based assay to monitor M-protein in multiple myeloma patients (EasyM), , , 2021

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.

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Mass Spectrometry Provides a Highly Sensitive Noninvasive Means of Sequencing and Tracking M-Protein in the Blood of Multiple Myeloma Patients, , , 2021

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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Rapid and Accurate Detection of Aminoglycoside-Modifying Enzymes and 16S rRNA Methyltransferases by Targeted Liquid Chromatography-Tandem Mass, 2021

This publication by the Dekker group describes the development of an accurate and rapid targeted LC-MS/MS assay based on parallel reaction monitoring for detection of the most prevalent aminoglycoside-modifying enzymes and 16S rRNA methyltransferases in Escherichia coli and Klebsiella pneumoniae that confer resistance to aminoglycosides.

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R1441G but not G201S Mutation Enhances LRRK2 Mediated Rab10 phosporylation in human Peripheral blood neutrophils, , 2021

This publication from University of Dundee led by Esther Sammler, describes that in vivo LRRK2 dependent

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Deciphering the LRRK code: LRRK1 and LRRK2 phosphorylate distinct Rab proteins and are regulated by diverse mechanisms, 2020

This publication from University of Dundee led by Dario R Alessi, describes how LRRK1, a less studied homologue of LRRK2 regulates growth factor receptor trafficking and osteoclast biology reinforcing that the LRRK enzymes have evolved as major regulators of Rab biology in Parkinson’s disease.

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Development of a multiplexed targeted mass spectrometry assay for LRRK2-phosphorylated Rabs and Ser910/Ser935 biomarker sites, , 2020

This publication from University of Dundee led by Dario R Alessi, describes the validation and development of a new, multiplexed targeted assay that enables the relative quantification of the key components of the LRRK2 pathway, defining the impact of LRRK2 inhibitors and Parkinson’s disease causing mutations.

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Peptidomic analysis of urine from youths with early type 1 diabetes reveals novel bioactivity of uromodulin peptides in vitro, , , 2019

Urinary peptidomics in early type 1 diabetes

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Robust and Reprodusible Protein Quantification in Plasma Using the Evosep One and the Agilent 6495 Triple Quadrupole LC/MS, , 2020

Agilent feasibility study

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Targeted assay development for quantifying protein half-life over a range of mouse tissues, , 2019

Protein turnover

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Development of mass spectrometry-based targeted assay for direct detection of novel SARS-CoV-2 coronavirus from clinical specimens, , , 2020

This publication by the Akhilesh Pandey group describes a targeted FAIMS-PRM assay on an Orbitrap Exploris 480 MS. More than 700 nasopharyngeal swab samples were analyzed with high specificity and comparable sensitivity to the gold standard RT-PCR method for the diagnosis of SARS-CoV-2.

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Accurate Detection Of The Four Most Prevalent Carbapenemases In E. Coli And K. Pneumoniae By High-Resolution Mass Spectrometry, 2019

“Proof of concept” study showing the potential of targeted high resolution MS in detecting different resistance mechanisms. Accurate detection of KPC, OXA-48-like, NDM and VIM carbapenemases.

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High-Throughput Proteomics Quantification Enabled by Fast LC Separation and Advanced PRM Acquisition, , 2018

High throughput LC-PRM to monitor the main protein components of AKT/mTOR signaling pathway.

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Fast Confirmatory Analysis of Rhuepos in Plasma for Horseracing Doping Control, , 2019

This application note describes a rapid targeted analysis monitoring two tryptic rHuEPO peptides in plasma for horseracing doping control. The results illustrate the promising capabilities of the Evosep One innovative technology for the analysis of protein/peptide-based drugs in the context of drug testing.

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