Multiple Myeloma Q&A: CAR T-cell Therapy, Steroids, Remission vs Cure, Kidneys, Bone Health, & More 

Dr. Joseph Mikhael:

Why do myeloma treatments stop working? Why are so many younger people being diagnosed with myeloma more than ever before? And if remission isn't a cure, what really is remission?

Hi everybody. Dr. Joseph Mikhael here, Chief Medical Officer of the International Myeloma Foundation. I host a live Q&A on facebook.com/myeloma, and we have so many questions that sometimes we can't get to them all, so I'm going to take some time today to answer as many as I can. Before I get into it, I want to remind you that the IMF has a whole host of educational offerings throughout the whole year, and you can learn about these virtual and in person webinars and seminars at events.myeloma.org. We believe that knowledge is power and we want you to be empowered. So check it out and come join us. We'd love to see you online or in person at our meetings.

Also, if you have questions, always feel free to use the hashtag AskTheIMF on any of our social media channels. If your question is a bit more private, feel free to call us or email us and one of our info line coordinators will be happy to answer your questions and help you navigate through multiple myeloma.

All right, let's get to it. First question comes to us from Priscilla and she says, "Have you seen paralysis after CAR T-cell therapy with Carvykti? I became paralyzed and I'm still learning to walk again."

Well, first of all, Priscilla, I'm very sorry that this has happened to you. It is an incredibly rare, but we know can happen, side effect of CAR T-cell therapy. CAR T-cell therapy, of course, is when we take T-cells out of a patient and basically train them as soldier cells to be given back to a patient and attack their multiple myeloma. A very small fraction of patients, less than 1% of patients can experience unusual, what we call delayed neuro toxicities, or a neurological event that happens later.

Typically, it may be something like a Parkinson's syndrome and sometimes it can even be paralysis. So it can happen. Thankfully, for the majority of patients, this will improve and we trust it'll continue to improve. If you follow more of our videos, I'll be sharing some of the new CAR T-cell therapies that we actually think do not have those associated neurological toxicities.

Well, let's come to another question. Here's one from Robin. "My husband died from myeloma, and years later I was diagnosed with MGUS, which later became multiple myeloma. How often do both partners develop multiple myeloma? This cannot just be coincidence."

Robin, I'm very sorry to hear about your husband and indeed about your diagnosis. This is actually quite rare, but all of us as myeloma doctors over the years have had couples that have both had multiple myeloma. We don't always understand the origin and the cause of myeloma. We think more often than not in this situation, it actually is coincidental because the precursor of myeloma, as you described, MGUS, is actually relatively common where one in 20 adults will have it.

Of course, myeloma is not as common, but it could also speak to the potential of other causes of myeloma that we are trying to discover and understand. We know certain things exist like exposure to Agent Orange, firefighters who have been exposed to repeated fires, other potential chemicals may be associated with multiple myeloma. But in general, we know that the vast majority of patients with myeloma, we don't know the cause of the disease.

Well, let's come to another question, a great question from Jen who says, "What are alternatives to dexamethasone for patients who develop steroid side effects like psychosis?"

Well, we use dexamethasone in multiple myeloma for lots of reasons. It actually has a direct anti-myeloma effect. When I started in myeloma over 20 years ago, dexamethasone alone was often given as treatment for myeloma, but we know it can also reduce side effects from drugs, particularly the infusional reactions where people can have a reaction to a drug. It can also reduce pain and it can also reduce nausea. So dexamethasone is a really important tool in the toolbox of multiple myeloma.

That being said, as you noted, Jen, people can have lots of different side effects, and sometimes as extreme as psychosis. So we can use alternatives, other kinds of steroids, things like prednisone and others that aren't quite as dramatic. Furthermore, we know that we can also use less dexamethasone than we used to use now that we have so many other options to attack myeloma, the role that dexamethasone plays is diminished. And so, I would encourage you to talk to your provider about using lower doses of dexamethasone as you're being treated.

Let's come to another question now from Dave. "I lift heavy in the gym six days a week," I'm impressed, Dave. Well done, "But could heavy lifting increase my risk of fractures with myeloma? I'm also getting my cells drawn for CAR T scheduled in the near future."

Well, I think it's very important, Dave, that you speak to your healthcare provider about your workouts. We've actually come to learn recently that exercise is a very good thing in cancer and in general, a very good thing in multiple myeloma. We do worry, however, about some of the extreme measures and the impact it can have on bones. Depending on how someone's bones are with multiple myeloma, some patients have almost no bone disease, some patients have more advanced bone disease. We may have to make recommendations about exercise.

Of course, there are many exercises that can be done by all patients, typically like being able to walk, or swim, or other low impact exercises. When it comes to heavy lifting, I would discuss this with your doctor because we want to make sure that you get the benefit of exercise, but not the risk of damaging the bones.

Let's come to another question that we have here from Donna. "My husband's myeloma responds at first, but always comes back quickly. He's now on his sixth line of treatment, and his tumor markers just jumped 1,000 points. Why won't doctors retry a treatment like Revlimid if it worked before?"

Well, I'm sorry to hear about the disease coming back, and unfortunately, we know that myeloma in general isn't curable and will come back. Sometimes when it comes back quickly like this, we say that patients have high risk myeloma or the kind of myeloma that grows quickly. More often than not, we don't go back to what has worked before because typically with drugs like Revlimid, when someone is on them, their disease does grow back.

When it grows back, it grows what we call resistant to the Revlimid, meaning it grows in the presence of Revlimid, so using Revlimid again is not likely to reduce the disease. That being said, if it was many lines ago, there are times we will go back to use drugs that worked before. This requires a good conversation with the healthcare team and a reminder of how important it is that we develop new treatments for myeloma so that we have new ways of attacking myeloma that the disease is not resistant to.

We come now to a question that is really a challenging, but I think important question. "If remission isn't a cure, what does remission really mean in multiple myeloma?"

If I walk out in the street and I ask somebody, "What is remission?" They tend to think about cure, but in myeloma, we don't use those two words in the same way. When we talk about remission, we talk about the disease coming down from its original level, typically by at least half of what it started at, and then hopefully staying in that level. I sometimes call this the depth and the duration of response is how we think about remission, but remission isn't a cure because unfortunately, typically with time, the disease will start to come back again.

When we think of cure on the other hand, if I asked you what people think of cure, they'll say, "Well, I guess I get treatment for something and I never have to think about it again." That's why we don't really talk about cure that frequently in myeloma, although there has always been a small percentage of patients with limited amounts of therapy in myeloma that actually stay in remission for a very long time that we essentially think of as cured.

Thankfully, that fraction of patients that maybe 15, 20 years ago was only four or 5% of patients, now is climbing to 10, 15, 20, and maybe even as high now as 30% of patients who will go into long-term remission. Another reminder of the importance of the research we're doing in multiple myeloma so that fraction of cure can grow higher, and higher, and higher.

Here's a great question from Sarah. "Are more young women being diagnosed with myeloma, or is testing just better now?"

Great question, Sarah, and very insightful. We do know that we are seeing more cases of multiple myeloma literally all around the world, especially here in the United States. We think that it has to do with a few factors. One, as you've already noted, we are getting better at myeloma awareness and testing so more people are being tested. We saw this in the past with breast cancer and colon cancer. As more testing was being done, we diagnosed more cases, not perhaps because there were really a surge in cases, but just more adequate testing to discover the cases that were there.

We also have seen an increase in myeloma as the population of the country ages because myeloma is a disease of older individuals. To see it more in younger women is likely more reflection of the better testing that we're doing. We hope, of course, that with time we'll learn the best way to test for myeloma and maybe even one day screen for myeloma before people have any signs or symptoms so that we can catch it even earlier.

All right, let's come to our last question that Susan asks. "I've had smoldering myeloma for six years, but now my kidney function is rapidly worsening. How can I know if my myeloma is causing my kidney damage?"

Well, thanks for this question, Susan. Very insightful. I'm sorry to hear that your kidney function is worsening, but it reminds us that when we talk about the kidney damage that we see in multiple myeloma, we talk about kidney damage that is indeed caused by the myeloma caused by the growth of those plasma cells in the bone marrow that produce the bad protein that can attack the kidney. When we see worsening kidney function, we typically also see a rise in the measures of someone's multiple myeloma, because of course, kidney dysfunction can happen for lots of other reasons, high blood pressure, diabetes, medications, other things.

And so, it becomes a diagnostic challenge, as we say, where we have to figure out why is this person's kidney function deteriorating and do the testing to determine that we rule out other causes and rule in multiple myeloma. I would have this carefully reviewed by your medical team, and it may involve a kidney specialist as well to help guide the therapy, and sometimes it may even require a kidney biopsy.

Well, that's all we have time for today, but thank you so much for asking these great questions. We love questions at the IMF, and we're here for you to help answer them. Don't forget, use any of our social media channels with the hashtag AskTheIMF and we'll do our best to get to your question as soon as possible.

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