What is a BCMA-directed Therapy? What are some FDA approved BCMA-directed therapies?

What is a BCMA directed therapy if patients progress on one BCMA directed therapy? Can they respond to another?

it's worth noting that there are multiple different ways that this is being done.

So CAR-T, which we know about, that's a way of basically reprograming a person's own T cells, which are T cells from the immune system or there specific type of cells from the immune system. We can reprogram those cells in the lab such that those person, a person's own T cells now go and attack cells in the body that have that BCMA molecule on the surface.

So that's car T another way is by doing of doing this is by using what's called bispecific molecules. So bispecific molecules are basically molecules that don't modify a person's actual T cells, but these bispecific molecules that are basically just what I call linker molecules.

what I mean by that is that one end of the bispecific molecule attaches to T cells, the other end of the molecule attaches to BCMA on the surface of the myeloma cells.

And so when this drug is in the body, it pulls myeloma cells in T cells together, activates the T cells, and that causes the T-cell to kill myeloma cells.

So that's another way of attacking BCMA. And then finally, the other popular way of doing this or the other common way of doing this is through monoclonal antibodies. So there are a number of these in cancer.

We use several of them in myeloma. There have been some of these developed in the BCMA space also, and these are basically proteins that go into the body. They stick to cells that have that became a molecule and that causes bad things to happen in the cell such that it kills them.

And so in terms of molecules or approaches that are available currently that are FDA approved, so there's two car TS, So there ida-cel which is a ABECMA, there's cilta-cel, which is CARVYKTI. Those are both FDA approved for people that have been through four prior lines of therapy for multiple myeloma.

And then the only other a currently FDA approved way of going after a BCMA is through this other molecule called teclistamab or tecvayli. And that's a bispecific molecule.

So basically two CAR-T is one bispecific molecule. That's it for BCMA directed therapy currently.

On April 5th, 2024, the FDA approved new indications for both CARVYKTI and ABECMA. The FDA approved CARVIKTY for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide.

The FDA approved ABECMA for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and an anti Cd38 monoclonal antibody.

Talvey and Elrexfio received FDA approval in August 2023 for myeloma patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti Cd38 monoclonal antibody.

And in terms of kind of how we choose them. So there is no there are no good studies currently to say which one's better, meaning that if we look at response rates, meaning how often these agents actually work to control myeloma. They control within

The vast majority of people, even with pretty advanced myeloma. So they're highly effective.

They don't likely cure people, but they keep the myeloma under control for a good length of time. You know, often more than a year, which is not great, but it's pretty good for for someone who's been through multiple lines of other therapy for multiple myeloma.

And again, they've never been tested head to head.

So we often think about the pros and the cons, and this is a long discussion in and of itself, which is to highlight them very briefly. A pro of CAR-T, for example, is that you give it once and you're done. There's no further therapy after that.

But the negative for CAR-T is that you often have to spend quite a bit of time at the center getting the therapy often a month just to make sure that things go okay due to side effects that can happen as a result of the CAR-T administration.

And then on the Bispecific molecules, for example, they're often not quite as complicated in the beginning. You can basically get in, get out more quickly. You don't have to spend a month at the treatment center, but those therapies go on indefinitely. So so unlike the CAR-T, which is a once and done, bispecific molecules, at least the way we use them currently and the way that teclistamab is FDA approved is that we use it indefinitely.

And then to your question about what's coming. So this is a huge field of research in myeloma currently. And so as I mentioned, for Bispecific, for example, there's one that's FDA approved currently, again, teclistamab, but there are literally probably ten plus other ones in development which also go after BCMA, but they're a little bit different.

Administration schedule is a little bit different pros and cons to all of them. But just to say that there's lots of other ones in development, and then similarly for CAR-T, there are lots of other ones that are coming also.

And then just to your question about how we sequence them and if we can use one after the other, the current answer we think is yes, in the sense that it would make sense that if somebody has been through, let's say BCMA Car T myeloma comes back, it would make sense to say, okay, we probably should avoid BCMA directed therapies because the myeloma’s seen that trick already

but it's actually been shown that especially for people that are more than six months out from their prior BCMA directed therapy doing another BCMA director therapy can and often does work.

So we're still, you know, lots of research going on in that field currently. But just suffice it to say that yes, we can do that and it often works and we do this pretty regularly in the clinics

BCMA stands for B-cell maturation antigen. It's a marker on on myeloma cells. And it's almost universally expressed on all myeloma cells. So that makes it a a nice, what we call targeted therapy.

And with the more recent advances in myeloma research, one of the key areas of exploration has been using the immune system to get a better response against the myeloma.

and one way to do that is by targeting BCMA.

And, there are currently three FDA approved therapies that we use.

one is a, an antibody based treatment, and the other two are Car T-cell or chimeric antigen receptor T cell therapies.

The antibody treatment is called teclistamab. And it's what's known as a bispecific antibody.

Now in contrast to what most may know, in terms of antibody treatments for myeloma, the most common being daratumumab, that's a monoclonal antibody. So monoclonal meaning that it recognizes one target on the myeloma cell. And in the case of daratumumab, it recognizes something called Cd38

Teclistamab in contrast has two parts to it. one part recognizes BCMA on myeloma cells, and the other part recognizes a marker on immune cells, T cells, and that marker’s CD3.

And so the way it works is that the antibody, once it's infused into the body or injected into the body, the antibody can latch on to myeloma cells with one of its arms.

And then with the other arm, it can latch on to an immune cell and bring them together to help the immune cell interact with the myeloma cell and kill the myeloma cell.

So that's basically how that treatment works. The other treatment that the Car-T or chimeric antigen receptor T-cell therapy, that is also an immune based therapy, it's different in that it's not what's known.

it's not an off the shelf pre manufactured treatment like the teclistamab is.

So in this case what we do is we take blood from a patient. And within the blood there are the immune cells, the T cells. Those cells are sent off to a special facility where they can genetically alter or modify the T cells to allow them to recognize BCMA.

And then those cells, once they've undergone the manufacturing process, are then sent back to the treatment center. And then those cells are then given back to a patient.

targeting BCMA in and of itself, if you have one treatment against that doesn't mean you cannot get another one.

We have done that actually for many of our patients where they get one and if their myeloma comes back, we've tried, the other available treatments.

the response rates, it's hard to actually know the what we call the real world data yet, because these treatments are relatively new. But we have seen fairly good response rates that are generally higher than, some of the, other treatments that we have available.

So we do oftentimes opt for those first.

To learn more about the drugs mentioned in this video, visit the link in the description.