Does enhanced genetic testing impact myeloma patients? | Santiago Thibaud, MD | #ASH24

So. Hi. I'm. I'm Santiago Thibaud, I'm a physician at Mount Sinai in New York City. And I specialize in treating multiple myeloma. I am going to talk about a recent, or a study that I am, presenting this year at this year's conference. But, before I talk about that, I need to, give some background or set the stage by talking about a different, but related research that we just published.

Back in September in the journal, blood cancer discovery. So in this, work, what we did was we had a very large, cohort of myeloma patients, nearly, seven, 1700 myeloma patients. And what we did is we analyzed, their, DNA. Right. And this is the DNA that they were born with, which is different than the DNA of the myeloma cells themselves.

And what we were looking for was, for the presence of mutations in their inherited DNA. That could, put them at, higher risk of developing some form of cancer. So these are well known mutations that are described in other cancer types that might increase the risk of, someone developing cancer in their lifetime and different forms of cancer associated with different mutations.

So myeloma is not really thought of as a hereditary, cancer. But, this data was not known how many myeloma patients have one of these mutations. So what we found is that the prevalence or the number of myeloma patients that have these mutations is actually, quite significant. About 1 in 10 patients with myeloma has some kind of cancer predisposing mutation.

And it's important to say that not all cancer predisposing mutations are, equal. Right. There are some that have more significance and more implications for a patient and their families. Right. Whereas others just, are associated with a a little bit of an increased risk of, of cancer. But nonetheless, it was a significant number. And, this project that I'm presenting this year is a follow up of that, and it deals more with the practical implications of this knowledge.

Right. So if these mutations are quite frequent, what if we can find a subset of myeloma patients that, really is at higher risk of having one of these mutations? And, what we found in our work was that patients who had had a different cancer previous, previously before they were diagnosed with myeloma or patients that had a very strong family history of cancer or myeloma, patients that were diagnosed at a very young age.

These patients were more likely to have one of these, mutations. So, what we did at Mount Sinai is we've been, referring patients who meet those criteria to be for a genetic evaluation. So they meet with a genetic counselor, and they, they, you know, they the genetic counselor gets a very thorough history of their, family history, etc..

And, then if it's indicated, they will offer, genetic testing and, so we've, now done this genetic testing in approximately, 50 some patients. And what we found was quite interesting. And was that, about 39% of the patients that we tested, actually had, we detected a mutation. So we go from that 10% in any myeloma patient to that nearly, you know, third, 40%, of patients who had a mutation.

When we look at this enriched group, right, this group that has a higher likelihood. So what this is setting the stage for is potentially, you know, there may be a need for us to think about referring for genetic evaluations, certain, myeloma patients who meet certain criteria. What we did in this analysis was looking at a very broad, panel of genes, all of which are tested, routinely.

This is not this was not, a research, panel, but rather, panel that is used in clinical practice for other cancers. Right. So a very comprehensive, gene panel. Yes. You're correct. And, that it was a Brca1 and Brca2 genes that showed a real enrichment in myeloma as compared to a control population. And, there is a couple of other genes that are, you know, BRCA related.

So they are involved in the same kinds of biological pathways. So one being PALB two, for example, and we're starting to understand that perhaps this pathway, has some significance when it comes to myeloma predisposition. It very likely is not the only pathway that is important for myeloma predisposition, but it is one that could be important and needs to be explored further.

So germline is a synonym for inherited right. So and variants is a synonym for mutations. So germline variants are inherited mutations. So these were it's essentially the same thing that I was describing mutations and these genes that are pathogenic. Right. So we talk in the paper, we talk about them as PGVs pathogenic germline variants.

And these are mutations in inherited DNA that are, known to cause a problem, right? That they are known to be pathogenic or to cause disease or to predispose to cancer. And, you know, there is today no real, you know, clearly demonstrated link between carrying these mutations and a higher risk of developing myeloma. But that is because it really hasn't been studied very much.

So we are we are, trying to develop that work further and, and see if we can identify any clear association. I think it's important to know a few things. And one is this is a work in progress. Right. So we are learning still at the learning stages of this. So, you know, I think, I wouldn't want patients, hearing this information and saying, well, I need to run and get tested, for these mutations.

Right? Because it is really not everyone that we are suggesting would benefit from undergoing this testing. But for those who have a very strong family history of cancer or meet some of these criteria, it could be something to consider. Why? Because, knowledge can be power. Right. And to know that one has that, increase in risk might have implications for the patient itself with regards to, you know, discussing with their doctors the need for starting to screen for other cancers at a younger age and also for family members.

Right. If some of these mutations are are passed on. Right. To children and it might be important for that reason, but again, not every patient it's worth discussing with, you know, their myeloma specialists or, oncologist and, and really see if that would benefit them or not.