Study Shows Promise for Non-Invasive MRD Testing for Myeloma Patients | Dory Abelman PhD(c) | #ASH24

Hi, my name is Dori Abelman. I'm a PhD candidate at the Princess Margaret Cancer Centre in Toronto, Canada, and I'm here at the American Society of Hematology annual meeting in San Diego to present our work on cell-free DNA whole genome sequencing for minimal residual disease detection and multiple myeloma. The goal of this study is to provide patients with a less invasive alternative to bone marrow aspirates for detecting minimal residual disease. We want to introduce this technology to benefit patients who live far away from a centre who don't want to come in to get a bone marrow aspirate and to enable more frequent monitoring, for example, by taking a blood draw every three months. So our test works with a blood draw. From that blood draw, we take the DNA and we get a mutational signature of around 10,000 regions which are unique to the myeloma. And the reason we're able to do this is because we're looking across the entire genome, so all the parts of the DNA, not just a few select parts which groups looked at previously. Using this method, we've had high concordance to standard methods like flow cytometry and clonoseq, and we've also started looking at other technologies like mass spectrometry of the M protein in peripheral blood called EZM. Based on our work, we're able to detect about 55% more MRD positive cases than standard flow cytometry or clonoseq, and when we compare that to the mass spec in the peripheral blood, we see a very high concordance, around 93%. We're hopeful that we'll be able to continue working on improving this method by adding more features which we can get from the DNA and eventually be able to offer it to more and more patients to offer them a less invasive way of detecting if they're MRD positive or negative. Our method currently, we take a bone marrow at baseline and then we get the mutations from that baseline marrow and then we look for those mutations over time in peripheral blood. This is different to standard flow cytometry or clonoseq which requires a bone marrow at every time point which you'd like to run the test. So typically, the first biopsy, a number of vials will be taken and then we can use one of the vials for our test and the other vials will go to standard, for example, FISH for molecular diagnostics. What we're hoping to do is also identify the variants which physicians normally use FISH for using our DNA approach. So we have been able to detect myeloma specific translocations like 414, 1114, and myeloma specific copy number alterations, and we're hoping that as we continue to improve this method, we'll have less reliance on that initial bone marrow aspirate for things like standard FISH because therefore you could use it for our test and at the same time get the myeloma specific variants. Because we're working with DNA and not M protein, it should in theory work for non-secretory patients as well. We have some patients on our study who are light chain only or who are non-secretory which have gotten this test and results seem promising in that cohort, but because we're not actually relying on the M protein as a protein-based assay would, for example, mass spectrometry, we don't have any limitations with that group. Princess Margaret Hospital in Toronto already offers this test for patients through the Ontario Institute for Cancer Research, so any patient there, if they have a high quality marrow sample available, could ask their doctor to order this test. We're hoping that as we continue to release data from our results that other centres will want to implement it in their centre too, and we can work together with them to help make it possible. I guess I could just say thank you to all the patients who make this research possible by donating their samples and enrolling in research programs. So I work with a lot of patients from sites across Canada and even in the U.S. and we hope that as we finalize our study we'll be promising and we'll continue to benefit patients in the future.