Navigating Priorities in the Expanding Myeloma Treatment Landscape
Navigating Priorities in the Expanding Myeloma Treatment Landscape from Patient Empowerment Network on Vimeo.
What should myeloma patients know about the latest treatments and monitoring? Expert Dr. Sikander Ailawadhi from Mayo Clinic shares updates about new research and treatments as well as new tools for monitoring myeloma progression and relapse.
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Transcript:
Lisa Hatfield:
Dr. Ailawadhi, can you speak to the latest news and priorities in the rapidly expanding myeloma treatment landscape?
Dr. Sikander Ailawadhi:
I think, Lisa, that’s an excellent and important question. Because as you rightly mentioned, there is such a large amount of data that is coming through for myeloma all the time. I mean, it’s almost, we kind of talk about the fact that every time you turn your shoulder or look over your shoulder, there is a new drug approved. So I can imagine this can be very overwhelming. So what I’ll say is that in my opinion, there are some categories of new data that are pertinent and important for our patients.
The two or three out of them that come to my mind, one is what’s called CELMoDs, or there are a couple of agents there called iberdomide, mezigdomide. These are showing some interesting data. Important to keep in mind that they are somewhat related to the immunomodulatory drugs lenalidomide (Revlimid), pomalidomide (Pomalyst), but they’re showing benefit in patients who have had len and pom before and have progressed. So exciting stuff there.
We’re also seeing some interesting data about newer CAR Ts and bispecific antibodies. They are all coming up with some benefits in some cases. I think it’s important to keep in mind that the bispecifics are landing at the 60 to 70 percent response rate, and CAR Ts are typically landing at the 80 to 90 percent response rate, but there are more agents expected.
There are also some newer bispecifics in different classes, like one of them is called cevostamab, which is an FcRH5 inhibitor or targeting bispecific. So newer bispecific, not just more of the same category. And there has also been recent data about Bcl-2 inhibitors, which have been traditionally used for patients with translocation 11;14.
There have been some negative data, negative as in trials, which did not pan out with a drug called venetoclax (Venclexta), but there are two other drugs that had some recent data shown from different companies, which were exciting information. So in my mind, those are kind of the broad new drug categories. There is another, a couple of other quick things that I’ll mention.
One is we’re getting more and more information about real world experience with these new drugs. It’s good to see that CAR Ts are panning out very similar in the real world as they are in clinical trials. We’re also seeing that the side effect profile of a lot of these newer novel immunotherapy drugs is similar as seen in the clinical trials.
Racial ethnic disparities are something which are very close to my heart, and there is more and more information coming out in that. Unfortunately, highlighting the disparities more still rather than yet coming up with solutions. And I think the last thing that I feel which has been recent has been at the American Society of Hematology meeting in 2023, which was in December in San Diego. One of the myeloma studies actually became a plenary session presentation, which is a pretty big deal for any disease area. So one thing is that it gets highlighted. Secondly, it was a combination of a regimen called isatuximab-irfc (Sarclisa) with carfilzomib (Kyprolis), lenalidomide, and dexamethasone (Decadron) in newly diagnosed patients.
It’s a randomized trial, Phase III, which was presented. I think the important part is we saw unprecedented deep responses and patients in much, much higher numbers than before becoming MRD-negative. So very deep responses. So these are kind of some very broad, but lots of highlights that I talked about.
Lisa Hatfield:
So can you also talk about some of the newer tools for myeloma progression and relapse and what patients might want to know about that? And in particular, maybe talk a bit about MRD testing and the role of MRD testing for patients who relapse.
Dr. Sikander Ailawadhi:
Excellent question. Lisa, I think the first and foremost thing an important part for our patients to learn is what are their “tumor markers,” for the, or disease markers for myeloma. We can follow myeloma by either the M spike or monoclonal protein, by light chains, by monoclonal protein in the urine or blood. And it’s important to keep that in mind because every now and then we’ll see patients who say, Hey, my ratio changed. So I’m progressing. Well, that comes after the light chains change. So it’s important to understand the role of these things. So M spike in the urine, M spike in the serum and light chains. One of them is typically the marker for a patient.
Now the MRD status or minimal residual disease that is looking for one cell, one myeloma cell from amongst 100,000 cells in the bone marrow. So it is looking at a very deep level. The most important benefit of MRD testing right now is to understand that if a patient turns MRD negative, then they have a superior outcome. Their prognosis is better. Their progression free survival, or the time before their disease comes back is longer.
But when a patient is MRD-negative and is being followed or maintenance or whatever, if the bone marrow turns MRD-positive, then that might be the sign that the disease might be coming back. Right now, we do not keep switching drugs to get to MRD-negative. That is not the goal of treatment. The way to think about it is we want to get to MRD-negative, but that means it’s incumbent upon us to try and pick a regimen that is more likely to get to MRD-negative. That’s the way to think about it.
Let’s pick a regimen more likely to get us into MRD-negative and hope that we get to MRD-negative. We see every now and then that the patients keep switching regimens just to get to MRD-negative. That’s not the way to go because you’re just using up options too quickly, too fast. A common question that patients ask is, well, does that mean I need to get annual bone marrow biopsies and MRD testing? Probably not.
That’s too much testing. So what I suggest is that once somebody has turned MRD-negative, it’s important to keep an eye on every single thing. Now, change in any of the routine labs, imaging, new symptoms, etcetera. That’s when we switch to the bone marrow again and see if the patient has turned MRD-positive. There are clinical trials going on right now which are stopping drugs based on repeat MRD negativity or starting drugs on MRD positivity. But those are clinical trial questions.
Lisa Hatfield:
So along those same lines, since you’re a Mayo physician, I’m curious about the mass spec testing. So if a patient say has been MRD-negative for some time, still wants to monitor at a deeper level, even though it’s not commercialized yet, do you see a role for mass spec testing on a regular basis in the future and being rolled out to community facilities also?
Dr. Sikander Ailawadhi:
Absolutely, Lisa. I did not specifically bring it up because mass spec is not, like you rightly said, is not yet commercially available. Now we’re doing mass spec quite frequently at Mayo Clinic. Basically mass spec is taking up a blood sample. Important to keep in mind, it’s not a bone marrow test, it’s a blood test, but it looks for those abnormal proteins based on the protein weight at a much, much lower level. Our SPEP or serum protein electrophoresis does not pick up very small quantities of the protein mass spec does. So in an essence, the mass spec, if somebody is negative on that, turning mass spec negative to mass spec positive may be an earlier sign of the disease coming back rather than the SPEP yet turning positive. But as you rightly said, it is not yet commercially available. I do see the benefit of it.
There is more and more data coming in favor of it, and there was data that was also at ASH. So I do see that in the future we’ll be able to most likely have it available more widely. At this point, it is just a blood test to attempt to check the disease level at a much deeper level and be able to notice if the disease is progressing sooner than our currently available tools.
