Q&A | Hope for High-Risk Multiple Myeloma: Latest Treatments & Life Expectancy Insights 

- What recent advancements offer hope for patients with high-risk multiple myeloma?

Hi, everybody. Joseph Mikhael here, Chief Medical Officer of the International Myeloma Foundation. And today, I'm gonna be answering questions from our high-risk multiple myeloma support group. The IMF has over 160 support groups around the country, many of them geographically based, but some disease-based, like our high-risk multiple myeloma group. You can learn more at myeloma.org or email them directly at [email protected] (mailto:[email protected]).

Well, lots of great questions have been coming in from this group, and we always encourage questions at the IMF. You can reach out to us in multiple ways to ask questions at myeloma.org. We have a chatbot at myeloma.org, affectionately known as Myelo. And indeed, we have our multiple social media channels. But let's get to these questions that were asked so that we can try and learn more about high-risk multiple myeloma.

Joe... I'm biased because whoever this person is must be great by their name. But Joe asks a great question: "What is the realistic life expectancy and quality of life for those with high-risk multiple myeloma? And how should I balance planning for bucket list trips with caution about remote travel destinations?" Well, Joe, I appreciate your candor, to be completely honest. And sometimes in medicine, we've not been totally open and honest with our patients, and I think that's critical that we do that. Typically, we define high-risk multiple myeloma as someone who has certain features that we know tend to speak to the disease growing a bit more quickly. And historically, the prognosis of high-risk myeloma was quite poor, to be very honest, where patients were not typically expected to live more than two years. But we all know that has changed considerably. It's hard to give an exact prognosis without knowing the details of every individual case.

But as we'll discuss when we answer these questions, we have come a long way in finding new treatments and finding better treatments for patients with high-risk multiple myeloma. But your question focuses on something very important, that when we treat patients, it's not just about quantity of life, it's quality of life, and we want them to have the opportunity to fulfill their bucket list. And I encourage all of my patients to have a bucket list, whether they have high-risk myeloma or standard-risk myeloma, and to work through that bucket because every day is a gift, and every day is an opportunity to enjoy the life that we have been given. And I don't say that in a glib way; I say it in a genuine way. That we want our patients now... With standard-risk myeloma, we expect our patients to live well over 10 years. And now, with high-risk myeloma, I would suggest that the vast majority of our patients will live more than five years. And that's based on the treatment we've had until now. We think it is gonna continue to get better. So thank you, Joe, for your candor.

And similarly, Cindy asks a question where she says, "What are the things that begin to happen when multiple myeloma is winning the battle? Is it time to consider that when we're nearing the end of life, to think about stopping some of our therapies?" And, Cindy, you ask, again, a very candid but important question. We all know that none of us are gonna live forever. And we've learned that when you develop a close and strong relationship with your healthcare team, and that team is aware not just of your myeloma but of you, of what your goals are, what your passions are, of what expectations are, that we can see how things are developing with myeloma.

It's very rare for someone to be living with myeloma and feeling well one day, and the next day, they're devastated by the disease and soon succumb to it. It's typically a longer process where we start to see it affect organs, we start to see it grow back, we start to see that it's more and more difficult to control. It's typically a very slow process, but it is very important to realize that there is a time and is very patient-dependent and is very appropriate to time, say, "I don't wanna be treated. I wanna focus on my quality of life and engaging our palliative care teams." And palliative care does not mean end-of-life care. Palliative care is focused on our symptoms, and engaging them earlier on in the discussion is really important so we can optimize people's benefit and quality of life throughout the whole of their treatment.

But yes, indeed, there are times when we know, unfortunately, it humbles me every day that there are times when myeloma becomes impossible to control. And it's important for us to recognize... I often say, "We don't treat myeloma; we treat people," and that we, in the most compassionate way possible, care for patients at the end of their life.

Here's another great question from Helga. Let me promise you that I did not plant this question. It's coming from Helga in Germany, and I heart Helga, 'cause she's asking a question very dear to me. She's referring to someone who's a 74-year-old active male individual with biochemical relapse after eight years with myeloma, being treated with daratumumab, Revlimid, and dexamethasone. Is now at the stage where they're on dara every month. But is there a possibility to drop the dexamethasone for sake of quality of life?

Well, the answer quickly is yes, absolutely. This is part of what I call the down with dex movement, as we're both seeing this in the clinical trials that we're designing and in the clinic, but we can use less dexamethasone. Dexamethasone is a great drug. It really helps, especially when we initiate treatment, because it boosts other drugs to tackle myeloma. It sometimes can reduce administration reactions like we have with the daratumumab or Darzalex here. It can reduce pain and sometimes even nausea. But with time, its positive effect is less, and its negative effect grows because it can affect people's blood sugar and blood pressure and mood and sleep patterns and weight and a whole host of things. So, very often, what we find is we start with dexamethasone for the first few months, then we taper it down. And I can tell you, in my practice, the vast majority of patients are off dexamethasone by about six months. So, this is something, Helga, to be discussed with the healthcare provider here, that there really is an opportunity to turn down the dose and indeed to discontinue.

Here's a great question: "Is there any data on high-risk multiple myeloma who had treatments, then did another FISH..." That's the genetic testing we do to determine if someone has high-risk disease. "To find that they are no longer in the high-risk category? Are they always treated as high-risk myeloma patients?" It's a great question because several people in the group asked it, and I get asked this very regularly. The short answer is, unfortunately, once someone has been designated a high-risk myeloma, we essentially keep them in that category for the rest of their myeloma career, as it were, because we don't really see a downgrading, if you will, to standard risk. Sadly, the reverse can happen. People can go from standard risk to high risk, and this is just a function of the way the biology of the disease works. Now, it doesn't mean that it can't be controlled, and this is maybe the most important take-home message I can give for all of the discussion around high-risk myeloma. The high-risk myeloma by itself is not a death sentence. It's not perfectly predictive. It does tell us that we're dealing with a more aggressive biology, but we need to approach it more aggressively to treat it. But we have high-risk myeloma patients that live very long and very well with this disease as long as we can approach it very carefully.

Sony asks, "Are there statistics on how long high-risk multiple myeloma patients survive without treatment, for how long they have not had treatment, and for those who have been on extended periods off of treatment?" A great question here, Sony. It's hard to compare individuals because, of course, everybody's different with myeloma. You know, as I've said, high-risk status generally puts people into a category where we expect their disease to come back more quickly, but sometimes it does not. And I think that's particularly important. So, I sometimes use this analogy; it's not perfect, but high-risk myeloma is like a red sports car. Chances are, on the highway, it's driving quickly, but it doesn't necessarily mean it has to. So, sometimes, a white Prius is passing the red Corvette. What I mean by that is just because the biology of the disease says that it'll grow quickly or drive quickly, it doesn't necessarily mean it's always doing so. We tend to be a little bit more cautious of going off all treatment in high-risk myeloma, with the exception of after CAR T-cell therapy, which we typically do in all patients because we know that myeloma can grow back more quickly, so we tend to use longer maintenance in high-risk patients. But we do know patients. We all have patients in our practice that have high-risk disease that go on long periods of time without treatment.

All right, let's come to our last question from Gail, who asks, "What recent advancements offer hope for patients with high-risk or even ultra-high-risk multiple myeloma?" Gail, I'm so glad you asked that question. I think it's a perfect way to end our Q&A session because I've been doing myeloma research for 25 years, and I don't know if I have ever seen a time where, in general, there's greater excitement about what we're achieving and what we're using in clinical trials and, indeed, in the clinic, but that's specifically now, we are doing much more work in high-risk myeloma, designing trials specifically for high-risk patients. And maybe one of the ways I can describe it to you is, in general, in high-risk myeloma, more is better. Meaning if we come at myeloma in multiple ways, typically in combinations, we can see better outcomes. And even now, with our new immunotherapies, we're starting to see combination bispecific agents or combining different strategies together. And particularly in that high-risk and ultra-high-risk category, we're seeing patients do better, not just 'cause they're living longer, but living better. 'Cause we're using treatments that are more tolerable and that are more conducive to people continuing to do the things that they want to do. So, it's not about one special magic treatment; it's about all the different treatments that we're using together and specifically designing them for patients with high-risk multiple myeloma.

Well, I'm always happy to answer your questions, and I hope you feel this has been helpful as we think through the specifics of high-risk multiple myeloma. Please, don't be shy. Reach out to us at the IMF. We're here for you. Whether you're a patient, whether someone in your family, or someone in your circle has multiple myeloma, we wanna hear from you. Reach out to us, please, at myeloma.org, and we'll do our best to help you through your journey.