A Multitude of Options in Myeloma
Dr. Robert Orlowski, Director of Myeloma and Professor in the Departments of Lymphoma/Myeloma and Experimental Therapeutics at The University of Texas MD Anderson discusses the multiple myeloma highlights and what patients can be excited about from the ASH 2018 meeting.
Esther Schorr: Hi there. This is Esther Schorr from Patient Power coming to you from ASH 2018 in San Diego, and I have with me today Dr. Bob Orlowski who has joined us at Patient Power before. He’s the Director of Myeloma and Professor in the Departments of Lymphoma and Myeloma and Experimental Therapeutics—that’s a very long title—at the University of MD Anderson—University of Texas MD Anderson. Sorry.
Dr. Orlowski: Thanks very much for having me.
Esther Schorr: I’m glad you’re here again.
Dr. Orlowski: It’s a pleasure to be back on Patient Power.
Esther Schorr: Thank you, sir. So what’s going on in myeloma now at ASH? What are the highlights? What are patients going to be excited about, and what are you excited about?
Dr. Orlowski: One of the exciting areas is definitely talking about the different therapies that are targeting what’s called BCMA or B-cell maturation antigen. This is a protein on the surface of myeloma cells, and the excitement about it is it’s a target which is almost only on myeloma or normal plasma cells, not on other kinds of tissues. And that’s important because if you want to target for immunotherapy, you don’t want that target to be on too many normal cells, or the immune therapy will kill those cells and cause side effects.
So there are really three categories of drugs now that are looking very attractive. One is what’s called an antibody-drug conjugate. So this is a plain old antibody that has another chemical attached to it, and it’s given usually IV right now, attaches to the myeloma cell. It then gets inside the cell and the drug is released. So the antibody is essentially like a carrier molecule.
Esther Schorr: Kind of like a cruise missile?
Dr. Orlowski: Sort of like that. I like that analogy, yes. And then it blows up, using that analogy, the cancer cell once it’s inside.
So one of the first of these drugs that already is in the clinic is showing a 60 percent response rate in very heavily pretreated patients. The registration study, meaning the trial that hopefully will get it approved by the FDA, has already finished enrolling, so we’re hopeful that maybe by the end of 2019 this drug as a single agent will be available. And it’s really easy to give. It’s IV once every three weeks, which is pretty darn good.
Esther Schorr: And what’s the drug called? I’m sorry I missed that.
Dr. Orlowski: Well, it’s a good question. Actually, it doesn’t have a name yet, which is why I didn’t tell you what it’s called, but the abbreviation for it is GSK 916.
Esther Schorr: Okay.
Dr. Orlowski: And the reason for that is it’s actually quite expensive to come up with a name, because they have to find a name that, first of all, is not confused with other drugs so that it minimizing errors and also one that us poor feeble-minded doctors will remember so that we prescribe it often.
Esther Schorr: We’re not sure how you can remember all the letters anyway. Okay. So that’s one. Is there something else going on that you got to share?
Dr. Orlowski: So a second category of drugs that target the same protein, BCMA, the first formal presentation of those data were shown here at ASH, and this is what’s called BiTE or Bi-specific T-cell engager. And it’s sort of is a molecule, if you want to use the cruise missile analogy, that has two war heads. One end binds to the cancer cell. The other end binds to the patient’s own T cell, brings them together and the T-cell attacks the cancer cell. So it’s a way to use immune therapy with the patient’s own immune cells, and there are reports here of the first one of these which is called AMG 420. Again, doesn’t have a name yet, but it’s showing in very heavily pretreated patients complete responses with MRD, or minimal residual disease, negativity, which is really exciting.
Esther Schorr: So and that’s different than—and we’ll probably talk about it in a minute—that’s different than CAR-T.
Dr. Orlowski: Exactly.
Esther Schorr: Okay. So we can talk about that in a minute.
Dr. Orlowski: Yeah, that would be great. So the next topic is the CAR-T, also against B-cell maturation antigen, or BCMA. It’s a little more complicated though because what you have to do is you take out the patient’s own T cells and then in a laboratory you infect them with a virus. The virus has a gene in it that expresses a receptor on the T cells so that they can better recognize the cancer cells.
Esther Schorr: An invitation.
Dr. Orlowski: Exactly. Kind of. I like that.
Esther Schorr: Okay.
Dr. Orlowski: And then you infuse the cells back into the patient. They find the cancer cell, they attack it, and they kill it. So it’s great, because it’s personalized. It uses the patient’s own T cells. The problem is that it takes two to four weeks to manufacture the cells after they’ve been taken out of the patients, and so in the meantime the myeloma can sometimes be creeping up. So that’s one problem.
And also there are activities with the disease or with the T cell against myeloma, but there are also some side effects like cytokine release syndrome. But the response rates with some of the more advanced molecules are in the 90 to 100 percent range, and the durability of that is at least a year to 18 months, depending on what patient population you look at. And those are the most mature data of the three categories of immune therapies that we’ve talked about.
Esther Schorr: So of those three are any of them being looked at for first-line therapy, or these are at the moment still for people who have relapsed or are more difficult cases?
Dr. Orlowski: Right now it’s more for very advanced disease, but there are already trials planned with all three of these technologists in earlier patients and some in newly diagnosed patients, especially those with high-risk disease, because they still don’t do as well with standard therapies that we have. So it’s really an exciting time because these are some of the best results we’ve had in very difficult to treat patients, which means they should work even better when we give them earlier.
Esther Schorr: So one other question then. What’s happened to stem cell transplants for multiple myeloma patients? With all of these new combinations of treatment s, where is that in the mix of consideration for treatment?
Dr. Orlowski: Stem cell transplant is still considered part of the standard of care for patients with newly diagnosed myeloma, and in some cases it can be used for relapsed disease, especially if the patient had a really good durable benefit with a first transplant. The advantage of the stem cell transplant right now is that it with works very well, the toxicity profile is very well defined, and compared to a CAR-T cell it’s actually relatively cheap. But as the technology hopefully becomes cheaper and more available there would be great interest in comparing outcomes of people getting chemo plus a transplant, for example, versus chemo plus a CAR-T cell.
Esther Schorr: So it sounds like there’s a lot more options that are coming up for multiple myeloma patients. Is there anything else that patients that are listening would want to know about, that they should feel good about?
Dr. Orlowski: Well, there’s a lot more data with other immune therapies including earlier use of daratumumab (Darzalex), which is an anti-CD38 antibody. One of the presentations, which is still to come on Tuesday, shows the data of that drug with lenalidomide and dexamethasone in previously untreated patients, and the results really look excellent. So that will probably be one of the new standards of care for transplant ineligible patients. And there are studies ongoing with daratumumab in transplant eligible patients as well.
Esther Schorr: That’s a lot.
Dr. Orlowski: And that’s not all of it, but I think that may be all we have time for.
Esther Schorr: Thank you so much, Dr. Orlowski, for being with us again and making this a little more comprehensible for us normal mortals.
Dr. Orlowski: Thank you very much.
Esther Schorr: This is Esther Schorr coming to you from ASH. And remember, knowledge can be the best medicine of all.
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