American Association for Cancer Research
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Figure S1 from A Personalized Mass Spectrometry–Based Assay to Monitor M-Protein in Patients with Multiple Myeloma (EasyM)

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posted on 2024-06-11, 15:00 authored by Mariya Liyasova, Zac McDonald, Paul Taylor, Kathleen Gorospe, Xin Xu, Chenyu Yao, Qixin Liu, Liqiang Yang, Eshetu G. Atenafu, Giovanni Piza, Bin Ma, Donna Reece, Suzanne Trudel

The sequences of heavy and light chains of M-protein of patient 001-001 obtained through de novo protein sequencing by MS.

Funding

Rapid Novor, Inc

Molly and David Bloom Chair

Canadian Cancer Society Research Institute

History

ARTICLE ABSTRACT

M-protein is a well-established biomarker used for multiple myeloma monitoring. Current improvements in multiple myeloma treatment created the need to monitor minimal residual disease (MRD) with high sensitivity. Measuring residual levels of M-protein in serum by MS was established as a sensitive assay for disease monitoring. In this study we evaluated the performance of EasyM—a noninvasive, sensitive, MS-based assay for M-protein monitoring. Twenty-six patients enrolled in MCRN-001 clinical trial of two high-dose alkylating agents as conditioning followed by lenalidomide maintenance were selected for the study. All selected patients achieved complete responses (CR) during treatment, whereas five experienced progressive disease on study. The M-protein of each patient was first sequenced from the diagnostic serum using our de novo protein sequencing platform. The patient-specific M-protein peptides were then measured by targeted MS assay to monitor the response to treatment. The M-protein doubling over 6 months measured by EasyM could predict the relapse in 4 of 5 relapsed patients 2 to 11 months earlier than conventional testing. In 21 disease-free patients, the M-protein was still detectable by EasyM despite normal FLC and MRD negativity. Importantly, of 72 MRD negative samples with CR status, 62 were positive by EasyM. The best sensitivity achieved by EasyM, detecting 0.58 mg/L of M-protein, was 1,000- and 200-fold higher compared with serum protein electrophoresis and immunofixation electrophoresis, respectively. EasyM was demonstrated to be a noninvasive, sensitive assay with superior performance compared with other assays, making it ideal for multiple myeloma monitoring and relapse prediction.