The Multiple Myeloma Channel is supported with funding from BMS (Gold) and Legend Biotech (Bronze).
VJHemOnc is an independent medical education platform. Supporters, including channel supporters, have no influence over the production of content. The levels of sponsorship listed are reflective of the amount of funding given to support the channel.
ASH 2025 | Utilizing cell-free DNA WGS for non-invasive MRD detection in multiple myeloma
In this interview, Dory Abelman, PhD(c), Princess Margaret Cancer Centre, Toronto, Canada, provides an update on the potential of using cell-free DNA (cfDNA) whole genome sequencing (WGS) for non-invasive measurable residual disease (MRD) detection in multiple myeloma (MM), highlighting how this technology performs when compared to traditional approaches. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Previously at VJHemOnc we’ve discussed some early work on this project. So we’ve now profiled 163 samples from 51 patients using cell-free DNA whole genome sequencing. We basically had a mutation list that we derived from bone marrow at the start. We found on average around 2,500 high-quality mutations and then tracked those over time in longitudinal samples to find a cumulative variant allele fraction across all of the mutations...
Previously at VJHemOnc we’ve discussed some early work on this project. So we’ve now profiled 163 samples from 51 patients using cell-free DNA whole genome sequencing. We basically had a mutation list that we derived from bone marrow at the start. We found on average around 2,500 high-quality mutations and then tracked those over time in longitudinal samples to find a cumulative variant allele fraction across all of the mutations. And the idea is if we have so many mutations, it’s like a needle in a haystack, but we have 2,500 needles and the odds of finding at least one is quite high with even 30 to 40x sequencing in the longitudinal peripheral blood cell-free DNA samples.
Overall, we see high accuracy to clono-seq and multi-parameter flow cytometry with around 90% accuracy between our cell-free whole-genome sequencing technology and our clinical comparators. Our technology also strongly stratifies relapse, with samples at one-year maintenance having 14% versus 100% relapse-free survival if they were predicted MRD positive or negative based on our technology.
And lastly, the quantitative probability of being MRD positive based on the number of mutations that we find in the cell free DNA correlates with time to progression with higher probabilities typically occurring closer to progression and the first increase in MRD probability after treatment occurring about 12.6 months on average before molecular clinical progression. So we’re hoping that this technology will help patients have less invasive alternatives for detecting MRD. And we did a preliminary validation in a cohort from the SPORE study, so from some US samples. Our other samples were Canadian. And what we’re looking for in future is to continue to validate this in larger cohorts and use our new 150 to 200x sequencing to see if we can recapitulate these results without the bone marrow at all. So just relying on the cell free DNA at baseline to derive our mutation lists.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
