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ASH 2024 | Cell-free DNA whole genome sequencing for non-invasive MRD detection in multiple myeloma
Dory Abelman, PhD(c), Princess Margaret Cancer Centre, Toronto, Canada, comments on the potential of cell-free DNA (cfDNA) whole genome sequencing for non-invasive measurable residual disease (MRD) detection in multiple myeloma (MM), highlighting its ability to detect approximately 55% more positives than traditional bone marrow-based methods. Dr Abelman notes that the technology may be better at detecting extramedullary sites or sites missed by single-site biopsy, and its non-invasive nature makes it more practical for sequential monitoring. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript
The way that our test works is we take a baseline bone marrow sample and we detect approximately 10,000 somatic mutations using whole genome sequencing in that sample and then follow up with that sample over time in peripheral blood cell-free DNA. Using our technology we have high concordance with other rates for MRD detection including flow cytometry and adaptive clonoSEQ...
The way that our test works is we take a baseline bone marrow sample and we detect approximately 10,000 somatic mutations using whole genome sequencing in that sample and then follow up with that sample over time in peripheral blood cell-free DNA. Using our technology we have high concordance with other rates for MRD detection including flow cytometry and adaptive clonoSEQ. But interestingly we’re able to detect about 55% more positives than those bone marrow-based methods.
We wanted to see if those were just false positive cases or if there’s other evidence of disease in those cases. So what we did is we looked at the M protein. We ran a technology called EasyM which is a mass spectrometry assay on the M protein in peripheral blood and found that in our cases which were missed by flow cytometry or clonoSEQ they were also positive by EasyM in 93 percent of cases so we believe that this technology is better able to detect extramedullary sites or sites which were just missed in a single site biopsy.
Given that our test is a lot less invasive than a bone marrow aspirate we think that it will be more practical and feasible for more sequential monitoring for example every three months to help a patient better understand if they’re coming out of MRD negativity earlier to better inform treatment decisions.
In the future, we’re looking at ways to further enhance the accuracy of our tests by looking at characteristics of the DNA molecule itself, for example, its fragment length or position. And also, we are exploring looking at mutation lists from peripheral blood at baseline for patients who don’t have a bone marrow available.
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