Detecting Minimal Residual Disease | Dory Abelman, PhD(c) | IMS 2024

Hi, I'm Dori Abelman and I'm a PhD candidate with the University of Toronto and I work at the Princess Margaret Cancer Centre in Toronto, Canada. I'm excited to talk to you today about our efforts to use cell-free DNA from normal blood draws to detect minimal residual disease in multiple myeloma. We all know the challenges with traditional bone marrow biopsies. We have a large needle which enters the pelvis area to pull up cells and the cells then go through various tests to help doctors understand a multiple myeloma subtype better and if it's coming back. Knowing if myeloma is coming back is very important for treatment decisions, for example, like if we need to alter the drug or to help a patient better understand how their disease is going and how their treatment is going. So in order to reduce the invasiveness associated with traditional needles, like those bone marrow biopsies, we're developing a method that uses just a regular blood draw, like when you get your vitamins checked. The way that this works is by pulling up the DNA called cell-free DNA, which broke off from the tumour and is just floating around in the bloodstream. And DNA has all the genetic information that we need to understand if something is cancer or not. What we used to do when we looked at DNA is to look for specific areas which we know are changed in the cancer. For example, a change in a letter of the DNA at a specific position, like a cancer gene, like TP53. The issue with that is it's just one needle in a big haystack. So instead, what we tried to do is look at thousands of mutations using full genome sequencing. What that means is instead of looking at the DNA only in one region, we look at the DNA from all the regions. And due to new technologies like advancements in DNA processing, sequencing and extraction, it's actually almost the same price or cheaper to just do the whole genome. So what we do is at diagnosis, when a patient is getting their bone marrow taken anyway, we'll take a little bit of that and sequence the DNA and find about 10,000 mutations or changes in the DNA on average, which we believe are associated with the cancer. And the way that we look at this is by also taking DNA from healthy cells in the patient. For example, other cells that are floating around in the blood, which we can capture from the blood jar, and then only taking the mutations that were in the tumor cells and subtracting them from those that were in the blood. What we then do is we look for those 10,000 needles in the blood over time. So after a patient has a stem cell transplant at 100 days post transplant, which is a common time point where a patient will come back to the planet, we'll get a blood draw and we'll look to see if we can find any of those 10,000 mutations in the blood. If we find a lot of them, then that's a sign that the cancer is still there. And if we don't find them, or we find very little, it's a sign that the cancer is likely gone. Our hope is to make this a test that patients can get maybe even every three months so that they'll have a really good understanding of if their cancer is there or not without needing to get a big bone marrow biopsy. Now we're currently working on this in a research setting, so we're still working out the quirks, but preliminary data, which I'm here in Rio to present about, shows very good concordance or very good similarity between other traditional MRD tests. For example, like flow cytometry, clonoseq, or EZM, which is a new test also at mass spectrometry, uses the protein sequencing of proteins that are found in the blood. So my hope is that over the next short while, as we finalize the algorithms that we use, that we'll be able to report on our findings and then make a clinical trial to validate if this test can improve patient outcomes in a much bigger cohort. And then from that, I hope that if this test is successful in the future research programs, that patients will have another option, a much less invasive option for detecting minimal residual disease and have a better understanding on if their cancer is coming back and also be able to make informed decisions then of what to do about it. So thank you so much for listening to me here in Rio at the International Myeloma Society Annual Meeting, and I'm happy to get in touch if you have any questions or want to talk about our work at the Francis Margaret Cancer Center further. Thank you so much.