What immunotherapies are used in myeloma?

What is immunotherapy?

Immunotherapy, like in broadly speaking, are drugs that sort of harness the patient's own immune system to attack and and kill cancer. Now, the most commonly used immunotherapy drugs like what most people with cancer think of immunotherapy are actually drugs that we don't use in myeloma. They're called the checkpoint inhibitors, drugs that release the brakes off the immune system so you are basically, you know, getting rid of those brakes and you're unleashing the immune system.

Those drugs didn't work out well in myeloma. So, you know, there was initially some disappointment, but immunotherapy in myeloma really kicked off with bispecific antibodies. Right. And then with chimeric antigen receptor therapy or CAR-T therapy, both of these therapies basically are utilizing the patient's own immune cells, a type of immune cells called T cells. And they're basically helping the T cell recognize a specific receptor on the myeloma.

Now, it could be BCMA. There are some other targets as well.

So you're basically teaching the immune cells to recognize and attack the cancer. That's something that we're very excited about.

What immunotherapies are being used in myeloma?

There are several classes of immunotherapies for myeloma today. Among these classes are monoclonal antibody therapies, which utilize laboratory made antibodies designed to target specific proteins on the surface of myeloma cells.

CD38 targeting monoclonal antibodies such as, you know, daratumumab and isatuximab, they technically., so, part of their mechanism of action also is immunotherapy. It works by different mechanisms. You're not you know, it's a little different conceptually from how Bispecific and CAR-T works.

But what you are doing is that you're sort of harnessing the power of the immune system and making that recognize that specific receptor through various mechanisms.

But yes daratumumab and isatuximab are also considered immunotherapy.

Monoclonal antibodies are going to keep on coming, I believe.

So we've got two that we have for CD38 and then we have one targeting SLAM or CS1, which is elotuzumab.

Those antibodies have turned out to be quite useful, particularly in combination with other drugs, but there are other antibodies coming.

One of the very interesting ones is called modakafusp, which is a anti CD38 antibody, but it's going to carry on its back an older drug that we used to use many years ago in myeloma called interferon and interferon is very important in myeloma progression. So this drug is going to come in and target that.

There's been some very preliminary data. I think it's going to be actually a very interesting approach. And you may start seeing other antibodies, kind of like how belantamab carries this monomethyl auristatin F on its back.

We're going to probably see that strategy used more and more in myeloma.

So there is something that we call an antibody drug conjugate.

so how. So, basically what blenrep or belantamab is, is that there is an antibody that targets a particular receptor on the blood cell. So that antibody will go and find that particular receptor. But then attached to that antibody is what we call a chemotherapy payload.

So think about it as this chemo, small chemotherapy bomb that is sort of attached to this antibody. So the antibody will find its way to the target. And then this chemotherapy payload or bond will sort of be released into those plasma cells.

So technically speaking, it is a way to deliver chemotherapy to those cells. I wouldn't personally call belantamab immunotherapy.

I would call it more in the lines of a more targeted way to sort of deliver chemotherapy specifically to those cells.

We are expecting to see these Bispecific drugs come out pretty soon teclistamab, which binds BCMA is approved in Europe, but not yet in the U.S. There's talquetamab, that targets GPRC5D. It looks very promising. So that is going to be coming up. There is cevostamab targeting FCRH5 I believe is the the right sequence.

Those are targets that we actually don't know what they really do in myeloma but they look very promising and these immunotherapies are being used in people who've already had anti BCMA therapy and failed it.

Tecvayli, Talvey, and Elrexfio have received FDA approval in the United States 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.

Car-T cell therapy probably will be the first to receive FDA approval. These are currently being investigated in late stage myeloma, but trials are already, planned and, will likely start, very soon.

Looking at patients, with specific, high risk profiles, who would likely derive greater benefit from a Car T-cell approach or potentially derive greater benefit from a Car-T cell approach than traditional, therapies?

Since the recording of this video, both Rebecca and Kavita Carti cell therapies have been FDA approved. Harvest can be used as early as the second line of therapy, and back as early as the third line of therapy.

There is a whole slew of CAR T's under development they're looking at other than B-cell maturation antigen as the target. There are bispecific CAR T being developed, Allogeneic transplants, which are not done very frequently in myeloma, are another form of immunotherapy. And they have kind of a checkered past in myeloma for a couple of reasons.

One is, studies were done back in the 1990s of allogeneic transplants, which had a very high mortality rate approaching 50% in three months.

And so they were really dropped at that point. But there have been over the years, some attempts at reviving that strategy. Now, one of the things that I think is very interesting, that may be another immunotherapy that takes in the good part of an allergenic transplant, leaving out the bad stuff is there is a development of allogeneic CAR T-cells.

So this is a strategy where you would take cells from a donor, now, not a donor related to you, but it would allow you to potentially go through a CAR-T transplant with an off the shelf product.

So I think there are those have been a little bit disappointing. I think you're going to see more about those. But I don't know if we're ever going to go back to a true allogeneic transplant, partly because although we can get the toxicity better, there still are people who relapse after they've had those.

So we don't do a lot of allogeneic stem cell transplant, meaning somebody, you know, donor stem cells. But that is also immunotherapy, right?

Like you're giving somebody else this brand new immune system to a patient with myeloma or some other blood cancer. So many would argue that that is also another older, probably less sexier form of immunotherapy, but it is still immunotherapy.

IMiDs are considered immunotherapy because among their actions, they do seem to have effects on T-cells. For example, they may actually augment T-cell function. So if we're using that as a definition of what is an immunotherapy, I think absolutely they fall in that category. They're probably, if you want to think about it, the oldest immunotherapies that we have in myeloma.

We tend to use immunotherapy for these newer, fancier drugs. But part of how, you know, immuno modulatory drugs work and there are many, many ways that we are still understanding about how immunomodulatory drugs work. But I would argue that even immunomodulatory drugs, part of how they work is by sort of stimulating the immune system and helping the immune system sort of recognize and attack myeloma cells. So in a way that is immunotherapy.

But we don't usually think of IMiDs, immunomodulatory drugs, as it's not the traditional classical definition of immunotherapy. We use that more for some of the newer drugs that I mentioned.

I should not fail to mention what are called CelMods and CelMods are kind of relatives of pomalidomide and lenalidomide. They are immunotherapies.

They look like they will work in people who have failed those drugs, but they're going to be oral, which is going to be pretty neat.

All of these classes of immunotherapies contribute to the treatment of myeloma. As research progresses, these therapies will expand treatment options, bringing more effective and personalized care for patients living with myeloma. To learn more about immunotherapies, watch our immunotherapies course for free on health tree.org.