What are BCMA-directed therapies?

What are BCMA-directed therapies?

Why do these therapies put patients at greater risk for infection?

How are infections being mitigated?

BCMA again, amazing target that we found for myeloma. And again, this is for almost everybody with myeloma. And we see it from patients who have MGUS or smoldering disease all the way to relapsed refractory. Sometimes we'll see different levels of BCMA that's on the myeloma cells themselves. But again, almost everybody has it. So very few people don't have BCMA to the point where I don't think I've had- I've had one patient that didn't have any BCMA out of the thousands of patients I see. Right? So it's a nice target for us to be able to use for everybody. Which is really important when we find targets. We've had targets in the past that only 20% of patients will have, or maybe 15% of patients will have, so we can't use it to get to the myeloma cells specifically.

So with BCMA, because it's for everybody, now we've attached everything to it. So all different kinds of therapy. So we have antibody drug conjugates. So they take a drug that they attach to BCMA, and once you get it, it goes straight to the myeloma cell. And then the drug goes into the myeloma cell there and kills the myeloma cell.

The idea is that we get it less in other cells and the rest of your body, but really concentrating it to the myeloma cell. The other ones, of course, are bispecifics. So a bispecific T-cell re-engager is basically we're trying to use your own immune cells to actually go after the myeloma. So we know that you have so many cousins of a plasma cell, which is a myeloma cell, that could have stopped the plasma cell from becoming myeloma and causing problems. But because they grew up together, sometimes the myeloma cell says, “Nope, I'm supposed to be here. You know, remember I'm your cousin. We're good,” and those T cells don't recognize that this has turned bad. Instead of a normal plasma cell, it's actually turned into a bad myeloma cell that's causing problems. So what we can do is wake that T-cell up. And one of them is the bispecific T-cell engager.

And the other one of course, is CAR-T cells. And so what we do is the engager is sort of an off-the-shelf way to do it, where I think of it as handcuffs. So it's a drug. It's a protein that goes in, it basically binds, it handcuffs the T cells that are in your body  as well as the myeloma through that BCMA. Right? So we say CD3 is the the flag that's on the T cell. So that's how it knows how to get the T cell. The other side, it's the myeloma with BCMA. And basically it activates the T cell and says, “Wake up! This is not your cousin anymore. This is not your friend. You need to kill this.” And so then it starts killing. That sort of the, again, whatever T cells you already have in your body that we're using them to go kill the myeloma. And then the more I would say direct way of increasing that T-cell response, we can actually take those T cells out of your body through something called apheresis. The T cells are already in your blood. So now we've, you know, taken them out, almost like a dialysis session. People know more a little bit about that. It takes about three hours or so. The rest of your blood comes back to you. We send those cells to a lab, to the company that's making them. And basically they put a new receptor in there. So receptors are how T cells recognize what they're supposed to kill. So normally T cells are supposed to kill infections for us. Pathogens, things that aren’t supposed to be there. And even cancer cells, you know, they do get rid of a lot of cancer cells for us. But sometimes they get tricked and that's how cancer then develops.

So now we can take a receptor for BCMA. So that way that T cell, instead of going after a fungus or whatever it was supposed to, is going to be directed towards the myeloma cell. So the BCMA receptor’s put into the T cells, then they're grown.So now you get, you know, millions of those T cells, and then we give them back to you after chemo. And again, now these T cells, they have night vision for BCMA. So because most other cells don't have BCMA, you do have some, and we'll talk about that
in terms of toxicity, but because it's mostly on myeloma cells, they now go in and start killing that myeloma.

Unfortunately, BCMA is also on just a few other cells. Like thankfully it's not on your heart or your lungs or your liver or kidneys, where if you had these T cells going after those organs, you would end up with organ failure and we don't want that. But it is on other immune cells. So there's some T cells that will have BCMA, there's B cells that help us with antibodies and in making antibodies naturally to help prevent infection. And so when we kill the bad myeloma cells, we unfortunately kill the good plasma cells and B cells and all these other immune cells that actually help us fight infections.

And that is why whenever you get a treatment for BCMA, especially the T cell redirecting, so either the T cell engagers or the CAR-T, we see a big increase in risk of infection. And so for both of those specifically, we actually give a lot of prophylaxis. So patients will get IVIG if their IgG is low, which again, IgG or normal IgG is an antibody in our body that helps us fight normal infections. And when your IgG is really low, so usually less than 400, we know that you're just at a higher risk of bacterial infections, but even potentially some viruses and other things. So when we give IVIG, patients not only increase their IgG, but they actually might get immunity to vaccines and other things that are, you know, antibodies that are in there as well. So it just helps improve their risk of infection. Or if you get an infection, it helps you fight it a little bit better so it doesn't become as bad.

The other one is prophylaxis for antiviral. So we do shingles all the time. We still keep going with that. And then PJP pneumonia. So this is a specific pneumonia that people that have low T cells like AIDS or HIV we always give these medications to and now we we do it for patients getting BCMA therapies and T-cell therapies because we're using up your T cells. So we need to make sure you get that prophylaxis.

And then there's some patients that we’ll give antibacterial prophylaxis to. If someone's had a lot of infections in the past, when we start these medicines, we might actually give them even antibacterials for a few weeks just to make sure they get through. That one is not everybody gets it, but specific patients that we might think are at higher risk.

And then vaccines of course. So we always tell people vaccines are really important. These therapies decrease your ability to make a response to the vaccine. But that doesn't mean it's not going to help you potentially still. So again, you're still at a higher risk of infection, but if you have even a little bit of immunity that can help you from, you know, just a regular cold or upper respiratory infection turning into a really bad pneumonia.

So all these things together, we're hoping that you don't end up in the hospital with an infection.