What are some common endpoints in myeloma clinical trials? -PFS, DOR, OS and ORR

In clinical trials, researchers use specific measurements, called endpoints to determine how well a treatment is working. Some of the most commonly reported endpoints include progression free survival, overall survival, overall response rate, and duration of response, often shortened to focus OS or and door. Understanding what these terms mean can help patients better interpret clinical trial results and compare different treatment options in this health tree. Video we'll briefly explain what an endpoint is and break down the meaning of focus OS and door so you can feel more confident when reviewing myeloma research and treatment data. What is progression free survival? So progression free survival means the time interval between the patients getting on on the study to the time that they are showing either a biochemical progression or a clinical relapse. So the definition of progression or relapse are defined by the International Myeloma Working Group. Generally for biochemical progression, patients can be asymptomatic, but they've had 25% or more increase in their myeloma markers. with two consecutive readings or a clinical relapse is someone who is presenting with a new clinical problem. They're either anemic, they start developing new bone pains insufficiency in a things that we attribute to myeloma. that's the 00;01;27;07 - 00;01;28;02 Unknown time cutoff. that measure of time. As for progression free survival. progression free survival duration of responses are generally outcomes that we look at on clinical trials, right when we're doing a clinical trial. We want to make sure that whatever therapy we're looking at is effective at, right? That's what we're looking for. Is this actually work. And so these are measures that we look at to say, yeah, this is actually something that's potentially better than what's available standard of care. How does progression free survival differ from duration of response? So progression free survival refers to the time from randomization on a clinical trial. So until the patient's enrolled in randomized to the time that the disease progresses. Duration of response is a little bit difference of duration of response starts from their first kind of response. for multiple myeloma patients, that might be the first. You've started treatment on the study and it's the first time you hit a partial response or a very good partial response. from that point on to the time you progress, that would be the duration of response. What is overall survival? overall, survival is the time of, from randomization to the time of death. it is considered to be like the gold standard outcome on a clinical trial. Right. Ultimately, we want to know if patients are living longer and surviving longer because of a therapy that we have to offer. Why is overall survival a challenging endpoint to use in myeloma? is a challenge, though, in particular for patients with multiple myeloma because they're living so long. So it's a good problem to have. But if you're waiting for patients to die to get that marker of overall survival and patients are living, 8 to 10 years plus, you're having to wait that much amount of time and longer in order to get enough patients to meet that outcome in order to report survival data. It also makes it challenging because it's hard to interpret whether survival is solely because of the one therapy that you got or subsequent therapies thereafter. And again, for multiple myeloma, it's a good problem to have, but it's hard for us to decide if the treatment has overall survival benefit or not because we have other treatments that are works really well after you get your initial therapy. And so that can certainly affect overall survival. It is a gold standard kind of outcome again for clinical trials, but it makes it challenging to use as an outcome because of that. On top of that, you need a lot of patients, you need a lot of time. And when you're talking about clinical trials, unfortunately that means you need a lot of funding in order to keep up with that number of patients. In that time to run a study. Why may progression free survival be a better endpoint in myeloma trials? So overall survival is the period after getting the therapy before somebody dies and that's a pretty defined moment. 00;03;56;03 - 00;04;02;25 Unknown the problem with using that as an endpoint is that many therapies may follow as a therapy that you're actually interested in. And those new therapies could sort of blunt the results. let's say therapy is twice as good as therapy. B ultimately people relapse after both and then they get a CAR-T cell that gives them three or four years then they get some other tools to me that gives them even more time and the people die around the same time. It doesn't speak for which therapy was better. 00;04;27;03 - 00;04;30;18 Unknown you really want to know which therapy is better, I think progression free survival. This the way to really measure efficacy of a therapy. What is overall response rate? people are often curious when they get started on new treatment. What is their response to treatment and response? In my Loma is sort of, 00;04;46;22 - 00;04;48;20 Speaker 3 we define it in multiple ways. we define it based on the reduction of their M protein or their light change. If it's more than 50%, it's called a partial response. If it's more than, 90% response, called a very good partial response. Or if it's complete reduction and elimination of the M spike in the blood in the urine. then it's called the complete, response. In addition to a standard complete response, stringent complete response, and stricter laboratory requirements requiring normalization of the serum free light chain ratio and 0% plasma cells in bone marrow, making it a more sensitive measure of deep remission. in clinical trials, when we're assessing a drug's efficacy or how well it has done, we use this term called overall response rate. 00;05;30;13 - 00;05;32;11 Speaker 3 it takes all the patients in that 00;05;32;13 - 00;05;33;07 Speaker 3 treatment arm 00;05;33;10 - 00;05;34;23 Speaker 3 basically combines them. whether it's r very good partial response, partial response or CR the combination of all of that is overall response rate. Includes patients who achieve at least a partial response or better, such as partial response, very good partial response, complete response, stringent complete response. So Or equals. All patients who had meaningful tumor burden reduction on therapy divided by the total number of treated patients in a study or clinical trial. It's commonly used in clinical trials to quickly show how effective a treatment is at shrinking or controlling myeloma. Understanding endpoints like progression free survival, overall survival, overall response rate, and duration of response can help you better interpret myeloma. Clinical trials and treatment results We hope this health tree video helped clarify these important terms. Be sure to watch the other lessons in this series to continue building your understanding of myeloma research and care.