(Guest Lecture): MRD Tests and Applications | MCRT Webcast: Minimal Residual Disease (MRD) Essentials: How Should Patients Interpret Results?

[Music] thank you very much for for joining us for what we think will be a very um interactive forum so that we can discuss what the implications are for mrd and um we thought uh we're going to open with some description of what to expect with mrd and how does that play into how we think about the management of myeloma and what you saw in that iceberg is really the fundamental description of what we think about mrd so let me just translate that if you main to the clinic into how we interpret that information i'm going to put some comments some of them are very basic but i think it's very important because there can be confusion as to how we use mrd now in the clinical setting and as you know mrd stands for minimal residual disease some people prefer the term measurable residual disease and doctors argue for hours about this but we certainly are talking about the same thing and what we're talking is about medical methods to go deeper in our ability to detect any residual cells that may stay behind in a person's body after you complete a phase of treatment now there are several ways in which that can be done there's uh measurements that mrd that can be done with the testing that includes genetic testing which is uh one of the most commonly used and is the one uh that has an fda approved test which is going very deep with the sequencing technology to see if we can detect cells and i'll explain in a second how that plays out there are other methods where pathologists can use a series of dyes and then they they can pass sales through a computer system and some of these computer systems can measure thousands and hundreds of thousands of cells and they see if they can find a profile through those colors that could identify any residual cells this is often what's called flow cytometry and lastly there are other methods that are currently being developed that include the measurement of proteins in the serum that might stay in a person so you take that from a blood draw and see if they see if the the disease is still detectable now let's start first with what does it mean in the clinic you know mrd is a perfectioning over the tools we have but it's important for diagnosis so it's a diagnostic test you know years ago if you wanted to detect colon cancer people had a series of x-ray procedures some of them we contrast and we know that wasn't sufficient so things have moved forward and then people did the colonoscopy and we have other better tools now for the detect the detection of colon cancer if you had a kidney problem people had to go to the radiologist and they got a contrast dye you know injected into their vein and then you only got a very rough approximation of what was going on with the kidney and mrd something similar it's a way in which we're perfectioning our ability to measure what's in the bone marrow and the reason is that by doing so we can better gauge what's happening with treatment so you saw from dr wolf there's that water level and that's kind of in the old days where we were satisfied that if we reached that it appeared that we were doing good but as the treatments got better and better it turns out that we want to go beyond that we want to go to a level where the disease is not measurable at all if at all possible with our combinations when i was in training 25 years ago plus just reaching what we call the plateau was enough because those were the treatments we had at the time then it became what's what's called a very good partial response that was thought to be a very good goal for treatment and then that was not enough and then we went to complete response and as you heard from dr wolf it's a bit of a misnomer because it may not be complete in all cases then we gave it a second last name which was the stringent complete response and that is the bone marrow was normal and then you know we had three light chains that were normal and that was a step forward but that was still incomplete and at the the cutting edge right now what we have for how we can detect any residual disease we have mrd so that's how we're using it now there are two ways in which you can use it one of the ways in which it could be used and it's not used yet is as a regulatory endpoint what i mean by that is as people run clinical trials many are trying to work and convince the regulators that they should accept mrd as one of the goals that would allow for faster drug approval and that's a conversation that's currently ongoing and of course becomes enriched because of you know how how the data keeps coming back showing that mrd is a very powerful marker the second way in which this could be used is actually in in the clinic or in clinical trials right now some of you and perhaps this will come up in the questions are working with doctors who are not yet familiar or not quite ready to use mrd and and and that's obviously something that continues to evolve it requires the you know participation of pathologists and the the physicians also to understand how this can be useful but at the minimum i can tell you that all new clinical trials and multiple myeloma contain mrd as an important endpoint so it is important for doctors even those who don't currently order mrd that they understand how this works and what it means and i can tell you from looking at the multiple clinical trials and we won't go into the details of drugs or wage trials but it's pretty consistent in the clinical trials if patients are able to reach this very deep status of response particularly if they can get into mrd negative that seems to be translating into better long-term outcomes so as a goal it's a good goal to have this this mrd negativity now we're going to talk about the nuances about that because this can be distressing as well it doesn't mean every patient is going to get into mrd negative and it doesn't mean that that's the only path forward but if you know no different right from the get go as a goal that's a good thing to to know and lastly just before before i stop i'm going to say that you know when when we think about mrd it's important to remember and this goes back to logic as you know we would learn in high school and in college it is impossible to prove a negative that is we can have someone who's mrd negative and we know that's the best possible response but we cannot take that as evidence to conclude that there could not be any residual cells in the person's body i wish it was different i wish i had that certainty as we talked to patients but mrd only goes as far as telling us from the sample you have or from the sample that was taken particularly from the bone marrow you can only reach a certain conclusion and that is amongst the x number of cells that were tested usually that's in the millions and that's why we use the terminology of 10 to the -6 that reflects in the millions that at that point you can't detect cells it's possible that in some other part of the body there could be some cells or a few cells but what you can tell us from what we can tell them from the sample we couldn't find any residual myeloma cells it still is excellent news that means that the person has achieved a very very deep level of response um in our clinical practice we we are doing this routinely we're doing this routinely in patients who complete a stem cell transplant so at the completion time and when we do the very thorough assessment of what we call the day 100 we do mrd testing and we're doing that also in patients who have sustained complete responses over time to see where the disease is at and we particularly have used the the assay of the clonosic assay from adaptive biotechnology as a backbone for what we're doing for that determination so with that i'm just going to conclude my introductory remarks i know we're going to have questions and we're going to have conversations but it's important that we all understand what it means because this will become a part of the conversation around clinical trials and clinical care for myeloma patients thank you