How do treatments vary between myeloma and amyloidosis?

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How do treatments vary between myeloma and amyloidosis?

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Yeah. So how did the treatments vary between multiple myeloma and amyloidosis.

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key to this is that they're similar but different.

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And this is why you know, I think it's important that people with amyloidosis are seen at specialty centers because people that don't do a lot of amyloidosis often think that it's just just like treating myeloma And if you read the textbooks in the literature on this, it sounds a lot like that. It's the same chemotherapy regimens,

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similar workup in some sense,

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but it's not quite that easy.

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And a lot of that has to do with the fact the similarities come from the fact that they're both plasma cell diseases. Again, they're really on the spectrum. Some people have more myeloma problems, other people have more amyloidosis problems. But it all boils down to abnormal plasma cells, abnormal proteins, light chains in the blood that are damaging the body one way or another.

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But the treatments vary a little bit and a lot of that has to do with the fact that

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tolerability of different medicines can be quite different for somebody with multiple myeloma as opposed to amyloidosis. And so probably the two most relevant ones, especially for someone with newly diagnosed illness, are steroids and then Velcade or Bortezomib

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steroids, for example, we use a lot of them in both multiple myeloma and amyloidosis.

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And one problem that we know about with steroids is fluid retention. And fluid retention and multiple myeloma can be problematic, but it's usually not dangerous. It means a little bit of leg swelling. People may get kind of puffy, but because multiple myeloma does not usually come with heart failure, people usually can tolerate the fluids and we clinicians make adjustments, but usually it's not a major issue.

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But we know that when we hit patients with multi with amyloidosis, with myeloma doses of steroids, that can often lead to huge problems with fluid retention. So the fluid because they often have heart failure to begin with so that they get the big dose of steroids causes fluid retention. That fluid goes into the lungs. And then before you know it, a week into their treatment for amyloidosis, they're in the hospital with exacerbation of congestive heart failure.

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one thing that we

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who do a lot of amyloidosis know is that we really need to be cautious about steroids. And for somebody who just does a lot of myeloma and amyloidosis, every once in a while they read the textbook and see the same dose of steroids. Okay, Just just do the myeloma recipe and it'll be fine.

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then another one is Velcade or Bortezomib. So typically, again, getting at the heart, one thing that we rarely see in people getting bortezomib is heart difficulties, specifically arrhythmia, which is almost a short circuit of the heart that can cause abnormal heart rhythms. And they can be life threatening,

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usually not an issue in multiple myeloma, because again, multiple myeloma doesn't typically affect the heart.

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And so usually that's not too much of a concern. But often in amyloidosis,

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patients have severe heart dysfunction. Amyloidosis really likes to mess with the electrical system in the hearts of the heart is already sort of on the brink in some people and kind of ready to short circuit and ready to have those arrhythmias or abnormal heart rhythms.

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And so some sometimes when somebody starts on therapy and you hit them with a full dose of Bortezomib or Velcade that you would use on multiple myeloma, then they can have an abnormal heart rhythm. And patients have been known to die of this.

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And so often when we do the bortezomib drug in amyloidosis again, those of us who do a lot of amyloidosis when patients have significant heart failure.

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We often start off on very low doses and then slowly increase depending on tolerability.

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So those are two things. And then another one that I'll just mention is that often patients with amyloidosis have low blood pressures because again, that amyloidosis messes with the nerves that regulate blood pressure. So they often run low to begin with, can have problems with lightheadedness and even passing out.

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And then similarly, amyloidosis also can cause problems with the nerves that regulate G.I motility. So basically bowel kind of contractions. And so constipation, diarrhea, nausea to some degree are also quite common in amyloidosis.

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The bortezomib drug loves messing with those things. Also, it can cause low blood pressure is it can cause problems with the nerves in the GI tract.

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And so for someone with multiple myeloma who doesn't have any of those troubles to begin with can still be problematic. But you can often kind of intervene as those problems kick in. Whereas for somebody with amyloidosis who has those problems to begin with, you can imagine that if they're getting full doses of bortezomib and start to get some of those side effects, there's not a lot of reserve there and you can get into trouble really quickly.

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So one major consideration in amyloidosis is just thinking about the fact that for light chain amyloidosis is to think about the fact that it's related to multiple myeloma. So we use a lot of the same medications and a lot of the same strategies, including even stem cell transplant. But we do need to be careful

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and not just say any myeloma treatment works in amyloidosis.

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Also, we need to do it carefully

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What do you do when a patient has both myeloma and amyloidosis?

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Which guidelines do you follow?

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It's a great question about what do we do when a patient has both multiple myeloma and amyloidosis? And this is really, I think, where expert evaluation comes in, because this is not in the textbook. They're really on the spectrum.

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And what I mean by that is, as I said earlier, most people with these disorders have straight up multiple myeloma. They don't have amyloidosis. And we know that because we've said that ten, 15% of people with multiple myeloma have amyloidosis, which means 85, 90% just have multiple myeloma. On the other side of the coin, amyloidosis is about 1/10 as common as multiple myeloma.

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So a small percentage of people just have amyloidosis and not multiple myeloma. So both ends of the spectrum, but then there are people in between who have some component of both and sometimes and what often what that often means is that people have what I would think of as clinically significant amyloidosis. So their prob primary problem that brought them in the clinic may be things like congestive heart failure or some of the kidney trouble that we see with amyloidosis.

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But then we do the work up

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for multiple myeloma as one does. Any time you're working up someone with light chain amyloidosis and they may have small bone lesions which you don't see in amyloidosis, that's a myeloma problem. Or they may. What's a common one

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is that we see some of the blood abnormalities which are now diagnostic of multiple myeloma.

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So the common one is light chains. So when patients have high levels of abnormal light chains in the blood that actually is one of the diagnostic criteria for multiple myeloma, even if they don't have some of the common clinical problems that we see in multiple myeloma, like high blood, calcium level, the classic kidney problems, anemia, bone lesions, those sorts of problems.

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But if you have somebody who has, let's say, a heart failure from amyloidosis and they have really high light chains, then clinically the person's problem is really the heart failure and the amyloidosis. But by blood work, they also have multiple myeloma. So there really is a spectrum to this. And then there are other patients who really do have both.

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They may have heart failure from amyloidosis, and on top of that, they have high blood, calcium levels and bone lesions from multiple myeloma. So back to your question. When we think about how to manage this, it really is looking at the individual patient and saying, where is this person on the spectrum? Is this really pure amyloidosis and almost an incidental diagnosis of myeloma based on the blood work, in which case we're going to manage them much like amyloidosis and on the other hand, if the problem is really much more a multiple myeloma and amyloidosis is a relatively minor contributor, then we may manage it a little bit more like multiple myeloma.

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But it's a real gray zone because there's not a lot of research in this field and that if we think about a lot of the data that we have for managing patients with either of these of these disorders, it's from clinical trials. And so if you look at clinical trials in multiple myeloma, they always exclude amyloidosis. And if you look at clinical trials in amyloidosis, they always exclude multiple myeloma.

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And what that means is that people who are in the middle on the spectrum, they cannot get on these clinical trials, which means that we don't have much data. So it's a challenge.

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How would a diagnosis of amyloidosis impact your myeloma treatment?

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it's possible that a patient with multiple myeloma could have amyloidosis found on their bone marrow specimen or on another tissue biopsy without having significant symptoms related to their to that amyloid.

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in that case, it's debatable whether it has any impact at all on the outcome of the myeloma.

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If a patient has concurrent symptomatic amyloidosis, it could have a big impact, specifically if it affects the heart or the kidneys

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in the case of advanced heart involvement,

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that can contribute significantly to the prognosis of the patient and puts the patient at risk for cardiac rhythm problems or progressive congestive heart failure.

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Progressive kidney involvement also is problematic, but doesn't have any sort of significance

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may require adjustments of medications.

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High dose chemotherapy with autologous stem cell transplant is a commonly used therapy in amyloidosis like it is in multiple myeloma.

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Less patients are candidates for it because of the way amyloid affects your organs.

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But for sufficiently fit patients high dose melphalan and is a very effective therapy

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and is associated with some of the most durable responses in amyloidosis.