Q&A with Myeloma Experts: Your Questions Answered

Dr. Joe:
So we gave you a lot of information. Now's your chance. One of the things, of course, we really encourage, I'll put a commercial in while the first mic is making its way to the first questioner, is that the IMF, we really want people to send us questions. So if you follow us all in any area of social media, LinkedIn, Instagram, Facebook, X, whatever app you like to follow, you can always send a question with the hashtag #asktheIMF and we'll do our best to try and answer them on a regular basis.
We do videos, we do Facebook lives, et cetera. Put a re-plugin for the info line for Myelo that hopefully some of you have gone over and live tested. Our chatbot Myelo is sitting out in the hallway this week. So make sure you get a chance to do that because we really want to take time to answer questions. So let's dive in with our first question here, Michael.

Speaker 1:
This is a question for triage cancer. Do you have any information on how you think the Big Beautiful Bill is going to affect us? That's one question because I read recently in The Wall Street Journal that the $2,000 cap might be going away. That was one. And two, that Medicare has lost their negotiation with two drugs, Keytruda and Darzalex, so that was just concerning to me.

Speaker 2:
Yes. I do not know specifically about the drugs, but we do have information on the big bill that happened. We actually did a webinar recently on how will this big bill impact you? We did it I think a couple weeks ago and we have a recording of it on our website. And I highly recommend anyone to go over that. We spent a ton of time getting ready for that bill or for that webinar. It was a big bill. And then we also have a podcast called How to Triage Health and we have one of our episodes about the big bill as well, so I highly recommend viewing those.

Dr. Joe:
Michael's here?

Speaker 3:
Yeah. Okay. This is for Dr. Joe. I am going to be celebrating my sixth re-birthday in October, and I'm going to be celebrating it with a new doctor because my old one has relocated out of state. If you were my new doctor, what would you want to know about me as a patient in our first meeting? What would you want me to tell you?

Dr. Joe:
Wow, I like that. Can you be my patient? No. Great. So I'm sorry that there's been a change in your healthcare team. I know sometimes that can be a little bit traumatic. I think what would be helpful is when someone takes over a case like that, obviously they should particularly spend time looking back, seeing what you've been treated with, what kind of myeloma you have, et cetera, so what the treatment plan had been. I think we have to expect that that objective side of things would be preset.

A few things I would want to know when I'm meeting a new patient. I mean, when I meet a patient, I always start with the social history. I always want to know what's most important to them in their life. I said, we'll get to your myeloma, but I want to know you as a person first. So I think obviously it'll depend on every physician will do it a little bit differently as to how that's going to be asked, but I would be ready to explain not just what's valuable to you, which I think is important, but what is really important to you in your myeloma treatment.
Beth shared with us so beautifully that now that we have this panoply of choice in myeloma, we guide those choices not just on are you high risk or standard risk, have you had this drug or not this drug, do you have light chain disease. We do a lot of that based on what your preferences are. So what's really important to you? What are the kinds of activities that you want to continue to do? What becomes important to you in terms of frequent visits to the clinic or not frequent visits to the clinic?

Those kinds of things I think would be particularly important. And then lastly, also in light of what Beth shared with us has come out a few times today is what is going to be the best way for us to communicate together, how comfortable and familiar you are with a portal, if they have a portal, or with whatever system just to set right off the start what that communication path can be.

I would suggest that more so than providing a 3D color model of your M spike over the last seven years. I've had some patients come with that. They're typically accountants or engineers. But other than that, I think being ready to have those discussions would be valuable. Great question. I can't say I've heard that question before. That's impressive.

Brian:
Hello, my name is Brian, and my question is more towards diet as it relates to myeloma, not diet as it relates to symptoms and things like that. I'm just having a hard time finding out can I still eat McDonald's or do I have to get grass-fed burgers. These little things are a big deal for me because my whole life I just kind of did whatever I wanted.
And now I'm like, well, I'm hearing about a lot of pesticides and stuff in our food. I noticed this could be a whole seminar in itself, but if some very basic information or somewhere to lead so I could have a little better idea how diet and myeloma being or if there's any research taking place.

Dr. Joe:
Anybody want to start with that? Beth, I figured, because I know you cover this a lot.

Beth:
I'll go. I spent a ton of time talking about diet, nutrition, and the research around. So there's this Dr. Urvi Shah from Memorial Sloan Kettering and she has investigated this human gut microbiome and the interaction of immune system and what you eat. At the end of the day, it's adding fiber in your diet is I think a very important thing for all cancer reductions.
As far as I call it the seafood diet. In my two senses, you see food and eat it, but in moderation. I mean, we don't want you to eat lots of high fat foods. Greasy foods might not agree with you, but I think a lot of things in moderation is just fine. There's been several Living Well webinars on nutrition and health. I think Donna, did you do one with your nutritionist at Mount Sinai?

So go to myeloma.org and you can watch some of these webinars. But the whole eating sugar feeds cancer, don't eat sugar, I'm not sure about that. If you want to have a piece of cake, go eat it, but just don't eat the whole cake every day. And so that's my impression on cancer. So anything in moderation. And if you wanted to have fast food, it's probably okay, but it might not always agree with you to do it every single day.

Dr. Joe:
Yeah. I mean, I think all I'd add is that everybody always asks the question, which I think is appropriate. I mean, there really isn't an ideal myeloma specific diet. I think a lot of it has to do with general nutritional principles that we've learned that are good for you in general to be aware of what you're taking in.

Almost every nutritional guidance that I've seen, whether it's from cardiology, endocrinology, other, there's always that flex for a little bit of 10 to 20% junk as it were. So meaning the point about saying, "Oh, I have myeloma. I'm never going to have a piece of cake again, or I never have a cookie again."

Beth:
It's always the care partners that try to make you not eat.

Dr. Joe:
The only other thing that I add to it, so I think the point being that when you are nutritionally more stable, it's going to make it easier for you to undergo the treatments that we provide you because many of those treatments are going to put people through periods of time where they may not be able to eat as much, they may not feel as comfortable doing it.
And then the last point I always add whenever anything comes up about food intake and myeloma is obviously under the direction of your team as well based on one's status, but the importance of hydration cannot be under emphasized in myeloma because of its preponderance to go after the kidney. And so being able to ensure that people are well hydrated. One of the reasons why we have water on every table here, why there's bottles of water outside.

We don't want to skimp when it comes on keeping hydrated, especially in warmer climates like where we are now. So that becomes particularly important because that's an area that can often be missed in particular when people are on dexamethasone where people's metabolisms are turned up a little bit. All the things that we'll talk about how we love and hate dex I'm sure this weekend. So that's something always to keep in mind.

Speaker 4:
I just like to follow up with that. As a dietitian, I think all of the care centers and hospitals should have oncology dietitians that you can ask for a referral to. And I think that they would be very helpful to answer some of those questions.

Dr. Joe:
Yeah, I think one of the things that we've learned so much from ours as well is that we all have kind of misconceptions about food, about what we think might be good and might not be good, or even just how many calories are in certain things. So having that conversation can be extremely helpful. Thank you. Thank you for sharing that.

Michael:
You have a question?

Christine:
Hi, I am Christine. Kind of a question for Dr. Joe, I think, about the myeloma 101. My son was just diagnosed a few months ago and just went through a stem cell transplant, but what I'm wondering is that smoldering versus non-smoldering, he had a plasmacytoma to start with. Once you've had that, are you in a smoldering state when they just find one single plasmacytoma or you're not considered smoldering at that point?

Dr. Joe:
Yes, it's a really good question. So to clarify for everybody, plasmacytoma is sort of a unique term or word that we use when we think of a collection of plasma cells together. Now, technically even the word multiple myeloma refers to multiple tiny clusters of plasma cells. But when we use the word plasmacytoma, we're typically referring to a larger piece. So when I showed that spectrum of MGUS to smoldering myeloma to active myeloma, in fact, plasmacytoma may be sometimes outside of that spectrum because people are one of two situations.

There can be what we call solitary plasmacytoma where there's really just one collection of plasma cells. Now, I have to say this is becoming less common all the time, not because the disease has evolved, but because our techniques of detecting plasma cells in the body are getting so much better. We're starting to find that, oh, there's a collection here, but oh actually our PET scan shows that there's another little collection here.

And as soon as we see that second one or third one or fourth one, now someone has more systemic myeloma. The reason why the difference is important is often if someone truly has a solitary plasmacytoma, meaning we found this little lump and it's just plasma cells and there's no plasma cells everywhere else, sometimes those patients don't need systemic treatment, they may just have localized radiation.

But I have to say honestly, as we've done more and more sophisticated imaging and so on, the fraction of patients who truly have that is lower. So to answer your question, if someone has an isolated single plasmacytoma, it doesn't really fit, if you will, into the definitions of smoldering versus active myeloma. The issue there is, is it solitary or is it more than solitary? Meaning are there other ones? Are there other ones? Then we have to assume that there isn't just... You're not just going to radiate one and then radiate another. Then you're sort of...

Speaker 5:
Spot welding.

Dr. Joe:
Yeah, exactly. You're playing whack-a-mole and you're hitting ones popping up elsewhere. There is a source somewhere. That source is typically obviously the bone marrow. So that's typically how we make that distinction between them.

Speaker 6:
Hi. First of all, I love your ties. Every time I see you on Instagram, you've got a great tie on.

Dr. Joe:
I guess I have to buy some more ties now. All right, thanks.

Speaker 6:
First of all, let me say in my life I never got sick until all of a sudden this gnarly disease showed up in my life. When I got diagnosed with this, I went into treatment of lenalidomide, dexamethasone, like that. And stem cell transplant has been discussed, but one of the questions I have about it is because I have a healthy immune system or historically have, I know that the stem cell transplant and all of that wipes out your immune system completely and you have to start all over.

I'm not an anti-vaxxer, by the way. Is that harder on the system than doing the stem cell transplant to start all over with a completely new baby immune system that has had nothing? I don't know if that's a question.

Dr. Joe:
Yeah, no, it is a great question and let me try and explain it quickly. The notion of actually wiping out someone's immune system when we do a stem cell transplant is a little bit overstated. We're not actually entirely wiping out your immune system. In fact, even when people think about all the vaccinations you've had and so on, for those of you who've gone through a stem cell transplant, transplant center has this system where it's almost like we line you up with the babies and we re-vaccinate you and catch you up where you were.
For the kinds of transplant that we do in myeloma, the auto-transplant where you get stem cells from yourself, we actually don't completely deplete your stores. It goes down a little bit, and so we just want to make sure it's topped up because we want to give you every opportunity to give you as much immunity as possible. When people have an allotransplant, meaning they get stem cells from someone else, that's quite a different situation.

That's where the immune system is really... And we see a whole host of different diseases and infections and challenges in that patient population. So I'm not voting for transplant for you per se, but I'm just saying when someone says, "Oh no, I'm going to go through this transplant, I'm starting all over in my immune system. It used to be good, now it's going to be weaker," I wouldn't worry about that kind of line of thinking because we don't really eliminate the whole of your immune system.

Of course, the goal of transplant is to eliminate the myeloma that's in the bone marrow. It just happens to be there's some friendly fire that we hit enough of the bone marrow that we need to regrow it. But so many of the other elements of our immune system are preserved throughout. And of course, they're your stem cells. They were the stem cells that gave your immune system the first time round.

So we take them out and we freeze them. We give you the chemo. We give your stem cells back. So it's not like it's a different immune system. It's the same one that you had had, which is why unfortunately it's also not curative. Because your immune system gave rise to myeloma once, it'll likely give rise to myeloma again, but typically there's a long delay until it comes back.

Beth:
It's more of a rescue of your healthy bone marrow than a transplant.

Dr. Joe:
Got a question here.

Speaker 7:
Anybody want to ask me a question? How to raise money for his ties?

Dr. Joe:
Just to be clear, no IMF funds get used for my ties.

Beth:
Just Emily.

Dr. Joe:
Thanks, Sylvia.

Sylvia:
Hi. I'm just wondering if you do imaging at certain intervals for people because we all get blood tests every whatever number of months. When you're following someone, do you do imaging once a year or does it all just depend on the blood tests?

Dr. Joe:
Yeah, that's such a fantastic question and the aforementioned emotional support husband who's here is also a myeloma doctor who focuses in imaging. So Jens, feel free to correct me if I say something wrongly here, but the first thing I would say is we have really tried to develop better standards across the board so that there are guidelines, even guidelines that Jens and others have written, to give guidance here because historically, sometimes we were guided by what the insurance company allowed us to do or there wasn't clear consensus.

I would say I answer your question in two ways. Number one, it also depends on where someone's myeloma is. Because imaging, going back to the example I gave earlier of myeloma being literally like a crime scene, imaging can be even more important in certain types of myeloma. So if someone has had a lot of bone disease, if someone has had that extra medullary disease that I described earlier, I mean, I had a patient actually just in my clinic on Tuesday, the only way we can follow her myeloma is with imaging because she is a non-secretory myeloma.

There is no M spike. There's no light chain. Sometimes it's even hard to find a lot of myeloma in her bone marrow. So she is followed by imaging. So someone like that has to be looked at a little bit more routinely. If you look on the other hand of the so-called the average myeloma patient who's being treated and so on, with the way we treat now, thankfully the burden of bone disease tends to go down quite considerably after that first year.

And so in a situation like what you're describing, when someone is being routinely followed and their disease is under control, I would say that most of us are wanting to do some kind of imaging on an annual basis. Not absolutely required in every patient. There may be some very slow growing indolent forms of myeloma where there hasn't been a lot on imaging before.

That might cause us to do it even less frequently. But typically, we would do it on an annual basis. I would finally add that when someone's myeloma is waking up unfortunately and is relapsing, we typically want to fully restage that person, meaning we want to make sure that they get the right blood tests. We typically repeat a bone marrow, and we typically repeat imaging then as well.

So even if we say, okay, six months ago you had your annual PET scan, your disease is waking up now. We may have to repeat another one now. One, because we want to know the extent of the disease and to see if there's areas of risk, but also now to compare as you get treated, we want to see the improvement over time. I got the thumbs up from Jens. Okay, good.

Beth:
I think I just want to add.

Dr. Joe:
To keep my day job.

Beth:
I think with all these new T-cell redirecting therapies and all the exciting advancements you're going to hear over the weekend, there are I think a small percentage of patients that just like you heard, you only see it on bone disease. So it used to be once a year skeletal surveys. So we don't do that anymore. Those were low risk, not expensive. But really we're trying to do it about every year.

And I know Donna at Mount Sinai, their standard of care is a bone marrow biopsy annually and a whole body imaging with either a whole body low dose CT scan or a PET scan. And my favorite is the PET/CT scan in my practice if the insurance will reimburse. I don't think I have anything else to add, but it's about every year. And it just makes us so sad where everybody looks like they're in great remission and then you do a surveillance PET scan and there's new disease and it's a hard discussion to have.

Dr. Joe:
But rather pick it up early than...

Beth:
But rather pick it up early than... Yeah.

Dr. Joe:
Simona?

Simona:
My goal with my treatment is to have as little as possible, as I'm sure we all are. We travel a lot and my doctor has been wonderful in treating me in that way. I had a stem cell transplant. So I do a once a month treatment with Darzalex and Lenalidomide every day.

But I have high risk. I have two high risk factors. So I know this is only going to last for so long. So my question is about CAR T. What is the reality, especially for high risk? Because everyone says like, "Oh, it's great, then you don't have any more treatment or you're off treatment for a while." What is the reality of that for someone like me?
Dr. Joe:

Thank you for being so honest and open with us to share that. And as it stands now, one of the really great benefits of CAR T-cell therapy is that although there are some research studies going on in certain situations, we're typically not giving people ongoing treatment after the CAR T because one, it's so effective at reducing the burden of disease and the vast majority of people.

And two, part of the concept is that as I described briefly earlier when I explained CAR T, it's not just the Ts we've given back to you, but they can expand in your system and they can persist. One of the reasons why we think unfortunately some people progress soon after CAR T is that those CARs have so-called run out of gas, that they haven't been able to persist longer. And we're now trying to devise and design even more sophisticated CARs so that they can run longer.

I have a whole talk on whether or not we can get electric vehicles and all sorts of ways of thinking about longevity of those CARs. But for someone like yourself with the goal of wanting to be on as little treatment as possible, that often colors the discussion for the selection of CAR T. It's one of the reasons why a lot of our patients want to have CAR T because it's a little bit more involved. It's a little bit more intense.

There are some obvious risks that come with it, but then inevitably, patients are off treatment and often for a long period of time. My last comment to you would be when we looked at those patients that I commented on this morning or earlier this afternoon, in that CARTITUDE-1 clinical trial, those patients that went into that deep remission and stayed in it for over five years, there were high-risk patients in that group.

High-risk myeloma did not predict the inability to have a long response from CAR T. There were actually very little that predicted that. So we need more work to try and figure that out. But it wasn't like, oh, the standard risk people were the ones who got the longevity, the high-risk people, the ones who relapsed more quickly. So it's challenging our previous thought around how long something can last as a treatment in myeloma.

So again, I'm not trying to give specific advice for your case, but it is something I would consider because I think it'll hopefully meet your metric of trying to be off treatment. I think we have time for one more. Robin, is that okay? Where was the next?

Beth:
And you'll be here all weekend too, so you have more time.

Dr. Joe:
You can find me at breaks and things like that.

Speaker 4:
While you're talking about CAR T, I listened to a webinar a few weeks ago and was talked about is it called anito-cel?

Beth:
Anito-cel.

Dr. Joe:
Anito-cel.

Speaker 4:
Anito-cel, yes, which is a newer CAR T. Can you speak to that and what that's about and where we are in the approval process?

Dr. Joe:
Yeah, I can do that quickly. So we have two approved CAR T cell therapies right now. The first one that was approved first CAR T myeloma was ide-cel, which is short for a longer word that I will spare you all from. And the second was cilta-cel, and they both targeted BCMA. There are several other in development, some also target BCMA, some have different targets.

The one that there's been quite a bit of excitement around is this one called anito-cel. And partly because the design of the drug was a little bit different in the way that now these T-cells would interact with the immune system and with the target cell, with the hope that there would be greater affinity to hook onto myeloma cells and not to so-called traffic to other areas.

Although we don't fully understand some of the side effects that we see with CAR T, the primary side effects of CAR T are, one, cytokine release syndrome, which means the immune system kind of reacts saying, what is going on? Where did all these T-cell come from? And your body has this hormonal reaction to it. That happens pretty universally with all CAR Ts. But secondly, there can be infections, of course, because blood counts can be low and we've suppressed good plasma cells.

And the third issue are these neurological symptoms. And some of them we don't fully understand. I've said it often and I don't know if I've said it at this Patient Family Seminar before, but there is a mysterious love affair between plasma cells and our neurological system. And to be honest, we don't fully understand it. I've kind of always said a little bit like Travis Kelce and Taylor Swift.

Beth:
Well, that's obvious.

Dr. Joe:
I don't get it, but God bless you. All right. I'm obviously not commenting on them. But the point being is, is there something that we don't quite understand there? And there are some patients, unfortunately, who develop rather severe neurological effects. Often we see these mild neurological effects in the first few weeks after CAR T-cell therapy. We can see a little bit of as well with bispecific antibodies. But more often than not, they disappear.

It can be a facial palsy. It can be a little confusion. It can be a headache. I mean, there's all sorts of different things that can go away, but there are a few probably now in the range of about 2% of patients, hopefully closer to 1% as we've managed it better, who actually develop something considerably more severe like a Parkinsonian-like syndrome or Guillain-Barré or things like that.

Beth:
It's 5:00.

Dr. Joe:
It's too early to comment on it, but it appears that anito-cel has less of those neurological effects, which is one of the reasons there's been a lot of enthusiasm about it. And yet it still seems to have a response rate like we're seeing with cilta-cel over 90%. The jury is still out. It still has to go through the process. It has completed some initial clinical trials. It's going to take a while to go through the whole process, of course, getting approved. So we're looking probably beyond a year before it would be approved, but it's going through that pathway.

Beth:
And then when it's approved, it might be four prior lines too. It might be for four prior lines too.

Dr. Joe:
Right. So like most drugs in myeloma, it typically gets approved after multiple lines of therapy. So this is what happened with ide-cel and cilta-cel. They were approved after patients had at least four prior lines of therapy. Now we can use cilta-cel as soon as a second line therapy, and we can use ide-cel as soon as third line therapy. It'll likely start in that later sphere until the clinical trials are done earlier on. Robin, I think we are at time. Right at 5:00. But remember, we're here all weekend.

Beth:
Thank you, everyone.

Dr. Joe:
We're happy to take more questions over time. Thank you so much.