What should I know about the t(11;14) in myeloma?

n a previous HealthTree University lesson, we explored how multiple myeloma can be classified into six distinct genetic subtypes.

Now it's time to take a closer look at myeloma that displays the translocation 11;14.

What is translocation 11;14?

In multiple myeloma, you know, we have lots of what we called, cytogenetics and FISH testing that kind of tells us what the, the genetics or the programing of the cells might be doing. And so one of those is 11;14, translocation 11;14. And about 20% of patients with myeloma have this. Usually it's at diagnosis.

So sometimes we see genetic changes that happen over time as patients get different treatments. And their myeloma kind of comes back and it might come back with something a little bit different the next time. With the 11;14, it's one of those things that we usually see at diagnosis. And it usually continues through, all the different treatments we do.

11;14 basically means in your genes we all have every cell has 46 chromosomes. Right. And so, 23 are from mom, 23 from dad, and that does not mean you were born with, a problem in the genes. But once someone gets myeloma, for whatever reason, in that myeloma cell, patients had a part of their chromosomes 11 on one side and part of, chromosome 14, that when the cell was dividing those two sort of attached to each other, when that wasn't supposed to, and then it kind of replicated.

How is translocation 11;14 detected?

The way we figure out what people have in terms of these translocations and genetic changes is usually on the bone marrow, and sometimes on plasmacytomas that we've biopsied. We are working on blood tests. We're not there yet, but finding plasma cells or myeloma cells, anywhere we find them, we take them. And we, basically are pathologists will go through and do something called a FISH test that will see what changes are in that, those chromosomes. And that's how we figure out if someone has 11;14 or 4;14, 17p deletion. Again, these are all the different chromosome numbers that we're referring to.

Usually we'll see 11;14 at diagnosis. However the way the FISH testing is done is not, perfect. So again, why we're working on blood test eventually that will hopefully fix all these problems we have. But a lot of, centers will enrich the plasma cells, meaning that when we do a bone marrow biopsy and they're on slides, the samples are sent to the pathologist, and it depends on how they actually look for the test to say, is it going to actually be, quality assurance, right, that you actually are finding something or was there a false negative or a false positive? And the problem is the false negatives.

If you don't have at least 10% plasma cells, usually in the sample, the test doesn't work very well. So for some reason the biopsy itself when you were diagnosed didn't have very many cells, or you just don't have as much myeloma in the bone marrow that we might miss that, test at the beginning, that later on, if you end up with more myeloma, we might find it. But again, for majority of patients, we would think that it's probably at diagnosis. And then it just continues.

But there are some of my patients that, you know, we didn't find it initially. We thought the test was done well, and but then we found it later. So I still test for all my patients every time we do a bone marrow biopsy or a biopsy, we'll still test for as much of these as we can. The problem is that you can only do so many tests, sometimes with the sample. So again, once we get blood tests, I think it will change sort of these quality issues that we have. But, putting that into context, you know, sometimes when patients come to see me and maybe they didn't have 11;14 at the beginning, I'll still test for it to make sure you really don't have it.

What should individuals with translocation 11;14 know about targeted therapies?

The nice thing about the 11;14, translocation is that we have our first therapy that looks like it could actually target, patients with this change, with this aberration. So, something called, BCL-2 that's just a part of the pathway that's, increased for the myeloma cells with this specific change in that genetic, translocation that we can actually target that BCL-2 so that the myeloma cells are the ones that the venetoclax goes after.

So we've had lots of studies with venetoclax, with lymphoma and leukemia, and it's already actually approved for certain leukemias because it works so well. In myeloma, we actually had a study that included all myeloma patients initially thinking that it would work for everybody. And unfortunately, it actually didn't work for everybody and caused some toxicity for the patients who don't have the translocation or an elevated BCL-2.

So that study really showed us that this really should be for a group of patients that have just translocation 11;14. So now studies are being done in just that group of patients. And it's a great drug. I will say that all the myeloma doctors really like using it, usually in combination for our patients who have this, translocation issue, usually it's the second, third or fourth line. We don't use it upfront as of right now, because we have other therapies that also work for patients with this, which doesn't mean that all the other, you know, proteasome inhibitors and IMiDs and those things won't work. They work too.

So what we're trying to figure out is, you know, what combinations going to work the best and trying to get more of those options out there. A recent study that was presented, you know, showed that it didn't beat POMALYST or pomalidomide and dexamethasone, that was trying to get official approval for myeloma. Again, it doesn't mean that the drug doesn't work, but because it didn't beat it, which was what they were trying to show, in the trial and it hasn't become approved yet. However, again, we can get the drug, knowing that there's lots of patients that can benefit from it.

Is translocation 11;14, considered a high risk feature?

Unlike some of the other ones, translocation 11;14 actually isn't considered a high risk feature. So that that that's a little bit different than some of the other reasons why we do FISH.

Just testing.

What percentage of myeloma patients will have the translocation (11;14)?

Is translocation (11;14) seen in amyloidosis?

The 11;14 It's found in about 20% of all patients. Every fifth patient with my normal might have, the translocation 11;14, but, the, the there's a, as you know, the AL amyloidosis, which is very near as a diagnosis to myeloma, the expression that is about 70 to 80%, so and there is a target tested in lymphoma against this, translocation between chromosome 11;14 and the venetoclax. And we try it in, in my myeloma patient expression, expressing data t(11;14) with some responses.

What should amyloidosis patients know about using venetoclax?

Why the amyloidosis patients respond so well. I don't really know. But the responses to this drug with very low dose. We use 400mg accepted doses, 800mg. We didn't combine it with anything. And almost all patients responded.

How did they know that? It was an emergency. It a woman, 38 years old, of the intensive care unit with a severe heart failure. She was unconscious, and she was diagnosed with diagnosed with AL amyloidosis. We tried to move up, no effect. We gave a one week venetoclax, and the disease disappeared. And we did heart transplantation, and she, she's still alive. She's working 100% two years to date on the transplantation. And it was a desperate situation that learned, me, as a physician, I can use this drug to to and then tested it. And AL amyloidosis patients and almost everybody with the 11;14 response to the myeloma is another thing. Heart rate is only expressed in one fifth of the patient. Partly you need, to combine it with other drugs. Not only the venetoclax.

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