Hi, my name is Dory Abelman. I’m a new postdoctoral fellow at the Dana-Farber Cancer Institute and the Broad Institute in Boston. And the work I’m going to discuss today was completed during my PhD at the Princess Margaret Cancer Center in Toronto, Canada.
I’m excited to talk today about our work using cell free DNA for minimal residual disease detection and risk stratification in multiple myeloma.
Cell free DNA is DNA that broke away from basically the tumor or any other cells in our body which are floating around in the peripheral blood. And this is blood that we can sample, for example, when we get our vitamins checked and they take a blood draw from the arm. So what we can do is look at the DNA from all the cells in the body that’s found just floating around in the blood, and then pull out the tumor part of that DNA to learn about what the myeloma looks like without needing to go to a bone marrow.
As we know, bone marrow aspirate is really invasive and quite painful, and with durable remissions occurring for many years, where patients can now achieve deep responses for many, many years, it’s a lot of work to go and get a bone marrow aspirate every couple months, say for five years. We don’t want someone to have that kind of inconvenience.
So we wanted to offer a less invasive alternative for a patient to see if they’re minimal residual disease positive or negative during response, to have a good understanding of how they’re doing.
So we developed a test, which I spoke about before here, using cell free DNA. And we’ve since looked at it in a much bigger cohort of 51 patients, 163 samples. And what we found is that looking at mutations in the cell free DNA gives us a very strong understanding of if a patient has any residual tumor left or not.
We have high concordance with adaptive clonoSEQ, which is an NGS test done on the bone marrow, and using multiparameter flow cytometry on the bone marrow. So the peripheral blood gives us very concordant results with those bone marrow–based tests.
Also, the probability of a sample being MRD positive or negative, so the number of mutations that we see, correlates with the time to progression. And we can also stratify patients into high-risk groups that may benefit from earlier intervention during remission and those who are likely to have a very long, stable response.
Now, previously, this method was reliant on a bone marrow aspirate at diagnosis to get a mutation list that we could follow over time in the cell free DNA from the peripheral blood. But what we looked at, which I presented at this meeting, is how we did really deep sequencing on the cell free DNA to find those same mutations that we’d normally need the bone marrow for.
And this is from a new sequencer from a company called Ultima Genomics. They can give us very, very deep sequencing, like 200 times every fragment of DNA across the whole genome, compared to only 30 times which we were looking at before with the Illumina sequencer at comparable cost.
And what this does is it lets us find rare mutations that we otherwise wouldn’t be able to see in the blood. Using this method, we were able to find 88% of all the bone marrow mutations that we were looking for, and most of the driver mutations are very important for risk stratification.
So in future, our next steps are to validate these findings in larger cohorts. We’re also looking at copy number. We see that half of all of our patient profiles show some evidence of subclonal evolution of myeloma through the course of treatment.
And we’re hoping that this information will help patients get a better understanding of what their myeloma is looking like from the peripheral blood, if they’re in MRD positive or negative status, and if they may benefit most from a potential early intervention in the future.
Thank you so much for listening.
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HealthTree • December 19, 2025