Can You Take GLP-1s With Multiple Myeloma? CAR T, Revlimid & Treatment | Myeloma Expert Q&A

Dr. Joe:

Hi everybody. Dr. Joe here from the International Myeloma Foundation, and we love answering questions. Today I'm going to dive into several questions with you that have been brought to us by patients, care partners, long-term survivors, newly diagnosed patients, relapsed patients through all of our social media channels at the IMF, which includes Facebook, Instagram, X, and YouTube. Answering questions empowers patients and their care partners as they have conversations with their healthcare providers to decide what's best for their multiple myeloma. Some of these questions are deeply personal. Some of these questions are practical. Some are about science. Some are about newest treatments, some of the kinds of questions that I get every single day.

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Are GLP-1 medications safe for myeloma patients who need help with weight loss or insulin resistance? This is a complex question, but the quick answer is yes, as far as we know. We have now had many, many of our myeloma patients also treated with GLP-1 agents that have helped their insulin resistance, have helped them with weight loss, and it does not appear in any way to negatively impact their multiple myeloma. Now, of course, it's important to discuss this with your healthcare team so that they're aware of it. And interestingly, as a side note, there have been some interesting studies looking at whether these GLP-1 inhibitors may actually reduce the risk of progression of multiple myeloma. It's much too early to make any comment on it, but I find it fascinating that that is even being studied. So in brief, I think it's safe, but please discuss it with your healthcare team.

Let's come to another question from Tom who asks, "Is multiple myeloma hereditary, environmental, or both?" Well, Tom, the challenge is, for most patients, we actually don't know why they have multiple myeloma. In a very small fraction of patients, we can identify an environmental exposure that at least puts them at higher risk. The first of those is Agent Orange in our military veterans that have been exposed to it. Firefighters and other first responders that have been exposed to multiple fires, we know that they're at increased risk also of developing multiple myeloma, as well as some other rare toxic exposures. For some patients, there's no one in their family that has ever had myeloma. For some patients, there may be a relative with it. In general, we don't think of multiple myeloma as a hereditary disease, but there are some families that have several members of their family with multiple myeloma, and we're studying that extensively to try and understand it to see if we can predict it or be able to detect it earlier.

So in general, we don't know the cause of myeloma in most patients. But if you have had an unusual exposure, if there are other family members that have multiple myeloma or related diseases, discuss this with your team. Finally, I would note that whether someone has had an exposure or not, or has another family member or not, we typically treat myeloma the very same way. There isn't a different, if you will, form of multiple myeloma when someone has seen it in their family or has been exposed to things like Agent Orange. Great question.

Suzanne asks, "What progress is being made for primary plasma cell leukemia?" The timing of this question couldn't be better because we just had a very important paper authored by the chair of our board, Dr. Vincent Rajkumar, asking us to think about this diagnosis of plasma cell leukemia. And basically in his paper, he said, "We really shouldn't be thinking of plasma cell leukemia as a different disease to myeloma, but really just part of the spectrum of high risk multiple myeloma."

It's called plasma cell leukemia because, as you know, myeloma is a disease of the plasma cell. The plasma cell typically lives in our bone marrow, in our hips and in our spine and in our sternum. But sometimes when the myeloma is a bit more aggressive, it can escape into the blood and the word leukemia just means white cells in the blood. And so when those plasma cells are detected in the blood, we would call it plasma cell leukemia. But now with our more sophisticated testing, we know that actually most myeloma patients, if we look really, really carefully, will have some plasma cells in the blood. And so we're wanting to redefine this to not say that it really is a different disease, but it's really part of high-risk myeloma. We think that's important because sometimes on clinical trials and in certain insurance approvals, people have been denied access to treatment saying, "Oh, it's not myeloma, it's plasma cell leukemia." But plasma cell leukemia is really a form of high-risk myeloma.

And then lastly, to specifically answer your question, yes, there has been tremendous progress in high-risk multiple myeloma now that we can put plasma cell leukemia into that bucket. Because we are seeing patients living longer and better with high-risk myeloma as we use these newer immunotherapies and use them effectively for that group of patients. Thanks for the question.

Here's another great question from Karen. "If Revlimid maintenance is causing side effects, could stopping after two years be an option while staying on dara and dex?" Well, Karen, you've hit on a hot topic these days, which is the length of maintenance therapy. And in light of the recent ENDURANCE clinical trial, which looked at two years of maintenance versus ongoing maintenance, not being a big difference between them in survival, we are often talking about shorter times of maintenance, in particular in those patients that don't have high risk myeloma where we may want to continue it further.

But you've also highlighted an important point, which is side effects from maintenance therapy. We really don't want patients to have very many side effects in maintenance because maintenance is designed for a longer period of time. And so I think it's important to discuss this with your healthcare team. Because if those side effects are ongoing, often we can try to minimize them by reducing the dose of dex or sometimes even discontinuing it. There are patients who are on both Darzalex and Revlimid, like you've said, that may stop the Revlimid, but indeed continue the Darzalex. I would also note that we often tend to stop the dexamethasone as well because often the dexamethasone, as you mentioned in your question, the dexamethasone can be the one causing a lot of side effects as well. So in general, we are shortening time of maintenance therapy on Revlimid in non-high risk patients, and there are other options, so I would discuss this further with your healthcare team.

Sally asks, "How hard is CAR T-cell therapy on the body, especially for patients with kidney disease or heart issues?" I'm really glad this question was asked because in our early clinical trials with CAR T-cell therapy, we would typically exclude patients that had significant kidney or heart disease. But like with all therapies, as we use it more, as we become more comfortable with it, we're more willing to use it in patients who may originally have not been eligible. Obviously, this has to be discussed more fully with the healthcare team because there are very detailed nuances about how much the kidneys are damaged or how much the heart is damaged, because we do know that the process of CAR T-cell therapy does put some stress on the heart and does put some stress on the kidneys.

But for example, we now have protocols where we can do CAR T-cell therapy even in patients on dialysis. So this can be done, it has to be done carefully, but it has to be done in partnership typically with our cardiologists and nephrologists to optimize these organs so that we can give the therapy and allow patients to have the benefit of CAR T without excessive side effects. That being said, there are some patients who unfortunately, because of their heart condition, are not going to be eligible for CAR T-cell therapy, which is why we may be looking at alternatives such as bispecific antibodies or antibody drug conjugates.

We've had some great questions so far, but I just want to pause for a moment and emphasize the importance of asking these questions. You may have a question that is actually really going to help others. So if you have a question literally about anything in multiple myeloma, the diagnosis, treatment options, MRD negativity, clinical trials, side effects, please include them right here in this video down in the comments section, just use the Ask the IMF hashtag and we'll work hard to answer your question. Also, if you want to ask a question in person, make sure you learn about our in-person seminars that are coming to a city near you, and you can learn about those at events.myeloma.org. All right, let's get back to these great questions.

Let's take another question here where Jennifer asks, "Could newer immune therapies be used for patients in remission who were previously advised against CAR T because of side effects?" So Jennifer, I like how you refer to these as newer immune therapies can be used for patients in remission. We are trying to understand the best way and the best time to introduce these newer therapies. Typically, we think of introducing a new therapy when someone's disease is very active to bring it down, but now there are some of these treatments that we may continue a little bit like maintenance treatment that when someone has had already a remission from their disease to keep it there.

And so we are looking at those options, and what we are learning is that this disease is complicated. There's some patients that really respond well to CAR T-cell therapy and others who do not. We have patients who, when they do not respond well to CAR T-cell therapy, may very well respond to bispecific antibodies. So it's increasing the options that we have for our patients, and it is indeed something that should be looked at. Just because one immune therapy didn't work, it doesn't mean at all that the other immune therapies couldn't work for you and for other patients treated with their multiple myeloma.
Here's another question. "How long will it take before CAR T-cell therapy becomes mainstream for multiple myeloma?" Well, I could make an argument that it is already mainstream. CAR T-cell therapy when first approved almost five years ago was approved in patients that had four prior lines of therapy, meaning they had to have had four different relapses before we could consider CAR T. But now we can use CAR T-cell therapy as early as first relapse. And clinical trials are being done in bringing CAR T-cell therapy to frontline therapy. So it really has already become mainstream.

Part of the challenge in bringing it to mainstream was also the capacity that we had to manufacture these T-cells, and thankfully the factories have increased in the country. We now have more and more access to them.

Here's a question to us from Carmel who says, "How many rounds of myeloma treatment can someone have and how long can patients safely stay on treatment?" Well, of course, it really depends on what someone is being treated with. In the old days when we had very challenging chemotherapy, we could only give four or six cycles because it was harsh on the kidneys or on the heart or on the lungs. Now with many of these newer biological therapies, patients can actually stay on myeloma treatment for years. We have some patients who have remained on treatment for more than two, five, or even 10 years. So it really depends on the scenario.

But this is very important to discuss with your healthcare team because we are trying as much as we can in the myeloma community to have patients off therapies for periods of time. And this is now becoming more realistic as we get such deep responses to the treatments and such durable responses such that patients can remain in that remission for long periods of time. So as I often say, I love giving my patients no therapy and we're doing that more and more in multiple myeloma.

Here's a great question from Anne. "If my bone marrow shows myeloma progression, but I don't have lesions, why might my doctor still not recommend treatment?" Well, Anne, you're asking a really important question about how myeloma relapses. What do we find that tells us that the disease is coming back? Typically, we see changes in the blood or the urine tests or even in the bone marrow tests where the light chains or the M-spike starts to go up before we see true lesions in the bone on x-rays or sophisticated x-rays.

But just because we start to see a little change in the blood, we don't necessarily immediately invoke treatment. In some patients with higher risk myeloma or if their myeloma has proven to be very rapidly growing in the past, we may jump on it right away and treat. But by contrast, we may have some patients that have a very, very slow biochemical progression as we call it, meaning we see a tiny little change in the M-spike or a little change in the light chain, and it may be so slow that we have some time to make decisions about treatment, or sometimes it may take months and months before it really starts to grow. So this is the pace of someone's relapse, and this is a conversation to have with your healthcare team to determine when would be the right time. We don't want to wait too long and let those lesions develop, but we sometimes don't want to start too early when patients are feeling well.

All right, here's another question. I love the way you phrased this, Mohammed. "What is the best treatment for this monster?" Well, myeloma can be a monster. There's no doubt about it, although I'm very grateful that the monster seems a lot smaller now than it was in the past. We have seen huge progress in multiple myeloma with newer therapies upfront and in relapse that have given patients a deeper response, more durable, better quantity and quality of life. But the best treatment really depends on multiple factors. What kind of myeloma is it? Is it high risk or is it not high risk? The patient, what are their preferences? What are their other comorbidities, as we call it, or other health issues that might influence? And then of course, what are the options of specific treatments? And we try and match these three things together to choose what is best for the patient.

I always think this is important to emphasize because there really is no perfect therapy for myeloma. What's best for one patient may be very different than what's best for another patient, but overall, we've seen such an improvement in myeloma that we can remain optimistic that we are moving closer and closer to a cure.

Well, thank you everyone for asking these questions. These are truly remarkable questions. They're personal. They're really what patients and care partners are experiencing every day. If you have more questions, please send them to us. Use the hashtag asktheimf. We structure so much of our education around the very questions that you send in, and we know how important they are to you, and we want you to know that they're important to us.

Of course, the IMF is here for you in multiple ways. You can reach us at the website at myeloma.org. You can hear about the upcoming events at events.myeloma.org. You can call the info line or you can learn about our support groups at support.myeloma.org.

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If you're a newly diagnosed patient with multiple myeloma or just want to learn the basics of multiple myeloma, I would recommend our video, What Is Multiple Myeloma? A Simple Guide for Newly Diagnosed Patients. But if you have relapse disease and you want to learn more complex things about myeloma, you may want to watch one of our seminars that have been recorded where we learn about new options for therapy, the latest in science, and how we make decisions about the choices that we have for relapse multiple myeloma. And if you want to go deeper and learn more about relapse myeloma and the complexities of the science of myeloma, we have recorded many of our seminars and webinars that can be available to you to help you better understand this disease and the treatment choices that come with it. You can find those videos linked here.