Are there different ways to do MRD? Would MRD testing be multiple tests as a surrogate end point?

[Music] Are there different ways to do a MRD testing? There are at least three different, very different MRD assessment technologies. One is called multicolor flow cytometry. The second one is next generation B cell receptor sequencing, and the third is mass spec or mass spectrometry. Flow cytometry measures the number of cells based on characteristics that can be detected on a machine called a Flow Cytometer. Next generation sequencing looks for the gene that codes for the M protein that is secreted by myeloma cells, and that can be detected with very high sensitivity even in mixed populations of B cells. And mass spec is very different because it measures part of the monoclonal protein in the blood. Flow cytometry and the next gen sequencing, MRD's need bone marrow, the mass spec technology can be done on peripheral blood. Of those three, the mass spec technology is the least well developed at this point. So the likelihood is if and when MRD is adopted as a surrogate endpoint by the FDA, either the flow cytometry and or the next gen sequencing will be the ones that will be accepted. So there's still work need to be done to position the mass spec assay as a surrogate end point for clinical trials. Could MRD testing be used as a surrogate endpoint? So we use historical data to guide us because a number of clinical trials that have already been reported built in MRD testing at one year, post-treatment, two years post-treatment, there may be more frequent testing and there's been proposals to use consecutive testing at, you know, certain time intervals to be considered a full response. So MRD negative, two consecutive time points, three months apart or something like that would be considered, you know, the maximum response in a clinical trial. So these have to be thoughtfully designed and built into the future clinical trials where we are rigorously testing in a prospective manner, in a, you know, forward looking manner, whether MRD is actually an accurate surrogate endpoint. A lot of people want to know how we can use MRD. I kind of always make the joke that MRD is like wedding china. It's great to have, but you don't know what to do with it, right? We know a couple of things about MRD being MRD negative is being better than MRD. Positive. And you can correlate progression free survival with MRD outcome. So that's good. But how do you get there, too? We use MRD as a decision making point, and that we don't know yet, and we don't know if it's overall survival going to be a permanent endpoint. Because of that, it's imperative for us to do clinical trials where we use MRD to say, Hey, we're going to stop lenalidomide maintenance, or Hey, if we're going to add something because you're negative or positive and use that to guide our decisions and see what the data is, and then we'll be able to tell our patients, Hey, we got this sample. You're MRD, positive or negative, and now I can do something about that. Minimal residual disease is the deepest type of response. When you're MRD negative, that's a deeper response that we currently have. So in trials and gold standard, just look at overall survival. But that for a disease like myeloma, where people live several years, can take many, many years for a trial to readout as overall survival. So you need endpoints that you can reach quicker to help move drug development along more quickly also. So if you look at MRD level and you have a higher MRD level for a particular regimen, the suggestion is you're probably going to have longer progression free survival where people don't progress or even hopefully longer overall survival. So you can get to that endpoint much quicker. You can look at MRD just several months into trial or a year into trial. And so if you have a drug, for example, has 80% MRD and another one that has 30% MRD, you've probably got a better drug. So that's that's how our trials are using them right now. Can a new therapy be approved on a surrogate endpoint? It has been done in other cancers and now very sick patients. So certainly it's feasible. But we first have to prove that it is a good surrogate endpoint and there are some statistical rules, so to speak, before we can reliably say that this is a surrogate endpoint. Thanks for watching. By creating a health tree account, you can get exclusive access to the latest Health Tree University content. Track your course progress, take quizzes and bookmark lessons. Visit the links in the description below to get started.[Music]