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Belantamab Mafodotin and CAR-T Cell Therapy for Myeloma

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Published on July 17, 2020

How are Belantamab Mafodotin and CAR-T Cell Therapy Used To Treat Myeloma?

Hear the latest treatment options for people with multiple myeloma including the role of bispecific antibodies and CAR T-Cell clinical trial updates.

Host Andrew Schorr, Dr. Luciano Costa from the University of Alabama at Birmingham O’Neal Comprehensive Cancer Center and Dr. Joshua Richter of Tisch Cancer Institute at Mount Sinai discuss a new antibody-drug conjugate (Bela-Maf) and if CAR-T Cell therapy may reduce the need for stem cell transplants. Tune in to learn more.

This is the second of a four-part series. Click on the part to view the other parts in the series: Part 1, Part 3, Part 4.

This program is sponsored by Janssen Biotech, Inc. This organization has no editorial control. It is produced by Patient Power and Patient Power is solely responsible for the content.

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Transcript | Belantamab Mafodotin and CAR-T Cell Therapy for Myeloma

Dr. Richter:
The reality is the half-life of the drug is very long. So if you're already getting monthly, and you need to skip a month or two, the drug does not simply disappear over a matter of days. It takes quite a bit of time. So we held that therapy and it still maintained efficacy. But now that things have calmed down where obviously if patients are being maintained on oral therapies, we continue. But for those who need them, we are ramping back up with intravenous.

Andrew Schorr:
Some people and some myeloma patients are really into this. There's a drug that maybe is in late-stage, called BelMaf, and dr. Costa, maybe you can tell us what it is and apparently what's going on with the Oncology Drug Advisory Committee (ODAC) FDA hearing about it. So, what is BelMaf? Where would it fit in? And what's going to happen about approval, if anybody does?

Dr. Costa:
That's a great question. Belantamab Mafodotin is an antibody-drug conjugate. I think many patients are familiar with daratumumab (Darzalex), for example, which is a monoclonal antibody. So that's an immune protein that binds to a target in the cancer cell, and just recruits the natural elements of the immune system to kill that cell. With BelMaf, it's a little bit different, that antibody not only plays with the immune system and recruit the immune system but also has a payload. And the payload is a drug called MMAF (monomethyl auristatin F), which is a poison to the cancer cell, and keeps the cancer cell from dividing. I compared that with a kind of a target bomb, is that will deliver chemotherapy to the cancer cell and minimizing the side effects of the chemotherapy in all the organs.

So that's a brilliant idea that has panned out in other cancers. We have that in lymphoma, we have that in breast cancer, and so forth. This has been tested in phase I and phase II trial, that's called the DREAMM-2 study. And that's the study that effect the majority of patients had myeloma that was no longer responding to IMiDs like lenalidomide (Revlimid), to proteasome inhibitors like bortezomib (Velcade), or CD38 antibodies, like Darzalex. And those patients in general, don't do very well. That's a very difficult myeloma to treat. And on that trial a little bit over 30% of the patients respond. That's great, the infusion is very well tolerated. They have essentially no infusion-related reactions. The main challenge of that drug is that it cause low platelets.

It cause low neutrophils and that's common problems the patients are familiar with, and the doctors are familiar with, but also cause toxicity to the eye, cause corneal toxicity, which can be just blurry vision, but can be significant blurry vision that to the point that limits patients' activities of daily living. It seems to improve over time but oftentimes limits how long a patient can stay on the drug.

It's a little bit challenging for us because the myeloma physician or the medical oncologist, we are very comfortable maneuvering treatments around blood counts. We're not very comfortable maneuvering around eye toxicities, so that requires a lot of input and partnership from the ophthalmologist. So the other time there is this more fine balance between efficacy and toxicity. The FDA engaged the ODAC, there is an advisory committee that will reveal the evidence and provide a recommendation. It's not a binding recommendation, will provide a recommendation.

Andrew Schorr:
So, okay. So they're going to discuss the vision issues and we'll see where this drug goes, but the drug does help people with more advanced myeloma, a significant percentage?

Dr. Costa:
At least a third of the patients, and some of those for a long period of time.

Andrew Schorr:
So we know about thalidomide (Thalomid), we know about Revlimid, pomalidomide (Pomalyst). What's a cell mod? And what does that mean, Dr. Richter, for your armamentarium for myeloma?

Dr. Richter:
Sure. So, there are, of course, some differences, but for lack of a better term, they're the new IMiDs, the new Revlimid, the new Pomalyst. And there's a few of them out there because they're drugs that were manufactured by Celgene. Celgene doesn't really exist anymore. It was bought by BMS, but they're all called CC, for Celgene compounds. So there's CC-220, CC-422. CC-220 is the most advanced one, it's called iberdomide. And it's been studied in patients who have had a lot of other therapies, including prior IMiDs, like Revlimid and pomalidomide, and just as Dr. Costa pointed out, it seems that when given by itself in patients who've had a lot of these different therapies, it has a response rate of about 30%, so about one in three patients. But what the big benefit of this drug as is with BelMaf, is the combination studies.

So, as Dr. Costa pointed out, the DREAMM-2 study, so all the studies with BelMaf are called DREAMM, and there's DREAMM one, two, three, four, five, and so on. The data from DREAMM-6 combines BelMaf with Velcade, has a much higher response rate. So iberdomide is another pill. And there's a lot of studies now, these basket studies where they combine iberdomide with all standard therapies, iberdomide plus Velcade, plus Darzalex, and so on and so forth. And in combination, it seems to be very efficacious. So one of the really great things is a lot of people can benefit for drugs for long periods of time, and pills provide a way that people can go live their lives without being tied to office infusions.

Andrew Schorr:
Okay. Now, transplant has been standard for many people in myeloma. You have CAR T studies ongoing. Would that replace transplant? Dr. Costa, I don't know what advice you have for younger patients now, and where transplant still fits in?

Dr. Costa:
Oh, absolutely. So we’re all excited about CAR T, we are being involved with some of those trials, we have seen the data. When you have patients who essentially, whose myeloma essentially is not responding to any of the agents, and they go on a therapy where the chance of response are 90%. You can't help, but be excited and be hopeful. What we need to understand is the development now with CAR T, is on patients refactored to multiple lines of therapy. And if successful there, as it has been, the expectations is going to move to earlier, and earlier, and earlier. At the same time, you have autologous transplant, which is a cornerstone of the initial therapy of myeloma for patients who are fit to receive their therapy.

It's a proven therapy with proven safety, that has been shown over, and over, and over, to greatly prolong the duration of the remission and doing so, promoting the survival. So I think there may be a time when CAR T might come in and be a competitor for autologous transplant. I'm involved on about 150 transplants a year. I wouldn't mind to see that going away for a better therapy, but at this point, we're not there yet. So there's very few circumstances where you do one or the other. For the time being, CAR T is later in line in life, while autologous transplant is part of the initial therapy.

Andrew Schorr:
Okay. Dr. Richter, let's go on to a different area, bispecific antibodies. So we know Darzalex, and there are other antibodies, monoclonal antibodies. What's a bispecific antibody, Dr. Richter?

Dr. Richter:
Sure. So monoclonals are like Darzalex, rituximab (Rituxan), elotuzumab (Empliciti), those types of drugs, they've got one arm and they grab on to the cancer cell and they try to kill it directly. What a bispecific is, is it's got two arms, one arm grabs onto a target that's on the cancer cell. And the other grabs onto something called CD3, which is on our own T-cells, our immune cells. And it basically says, "Come here, cancer cell, come here, immune cell." And makes the immune cell kill the cancer cell. There's one of these drugs already approved in leukemia, called blinatumomab (Blincyto), and we have a large number of them in clinical trials for myeloma. And the benefit is that it's an off the shelf product. CAR Ts right now, most of them, not all, you have to manufacture, which takes three to four weeks in some cases. Bi functionals, from when they're approved, you could send someone in the back, that day they come in, and give them an infusion.

Andrew Schorr:
Hmm. Okay. Wow. So off the shelf. So that's attractive if it works. You talked about the horizon for something like this. Bispecific antibody, is this a year out, five years out? Do we even know?

Dr. Richter:
There's a large number of these, and we differentiate between them, they all have that CD3 that attacks the T-cell, but which marker attacks the cancer cell is different. We have some that attack BCMA, which is a target for many, which is a target for BelMaf and for CAR T's. We have some that attacks on a called GPRC. We even have in the attack CD38, like a fancy Darzalex and some newer ones called FCRH-5, which is another target on all cancer cells, are probably the ones that are farthest along. There's a compound called AMG-701, I don't think it actually has a name yet if I'm not mistaken.

I think we're probably about two years away - Dr. Costa, I don't know if you know any better, I think we're about two years away from that.

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