What is progressive disease? Is it the same as relapse?

What is progressive disease? Is progressive disease the same as relapse?

Progressive disease is when the myeloma starts to proliferate and start to come back, it starts to make its way back. We all knowthat myeloma is not a curable disease today, in 2023, for the vast majority of cases, it's very, very treatable. We have patients that lived decadesand the prognosis is improving very, very quickly.

And there are some patients who are what we call functionally cured, meaning they have such long remissions and the treatments work so, so well that they die of something completely unrelated.

So in that sense, yes, But in general, it's a relapsing disease. So you gain control of the disease with treatment. It may stay dormant or non-active inactive for a number of years, but it may eventually become resistant to the treatment. And the cancer cells can mutate and what happens is the treatment that worked all of a sudden doesn't work anymore.

And that's what we call a relapse. And luckily we have many, many treatments that we can change. So you may need to change therapy to account for the changes that occurred in the myeloma cells, get it back into remission, and then, you know, as long as that remission lasts, that treatment works.

progressive disease can be a biochemical relapse, which is just the blood tests going in the wrong direction. Person feels great progression of disease can be numbers look great. There is an M spike negative, M spike negative. But yet they fractured their femur. That's called a non secretory relapse, meaning the myeloma changed. It doesn't produce protein anymore.

we were, you know, we were thinking that it was quiet all this time and then all of a sudden it showed up in the bone.

That's very rare. It happens less than 10% of the time, but it's a reason to do bone imaging every so often just to keep an eye on, you know, the bones, because the blood tests or the biochemical tests don't always coincide with the bone tests or relapse can be something in the urine.

Sometimes the bones look good, the blood tests look good, but all of a sudden there's protein in the urine.

And we go and look at Why is that? Why is the kidney function getting worse? Why is there foam in the urine? And the protein levels are going up and it can occur that the myeloma is only affecting the kidneys?

It's rare, but it can happen. So there's many ways to define progression of disease.

Progressive disease: It has several different definitions. There are some strict definitions from the IMWG so the international myeloma Working Group, and these are if the myeloma markers go up by more than 20%.

But the absolute marker is the M spike has to be over 0.5 grams per deciliter and the light chains have to be over ten. And then I'm talking about the milligrams per deciliter as well. And then there are a few other markers as well. So there are some strict markers that we use in clinical trials. Of course, these are somewhat the markers that we're using in clinic as well.

So that's the that's what defines progression of disease. And there is clinical progression where you can also have symptoms. You can have, again, the crab criteria that can be president diagnosis. And then there's something called also biochemical progression where we start seeing in second go from MRD negative. minimal residual disease MRD negativity in the bone marrow.

To MRD positivity where we can start seeing hints that an M spike is coming up and that the light chains are coming up, but they haven't yet got to the point where it would be defined as progressive disease per the criteria.

So how do we use then the progression of disease or biochemical progression in the clinic? We do that in, we personalize it for each and every patient because it is different. If you have a young patient where you want to be very aggressive and keep the disease low as long as you can, or if you have an older patient with a very slow progression who is doing well on their treatment.

We want to keep that treatment going for as long as possible. So it's very different from person to person and then we decide when to switch on really on an individual basis.