New Myeloma Therapies: What Are the Current Trials?

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Topics include: Treatments

There are several new myeloma drugs being studied that show promise.  At a recent myeloma town meeting in Houston, Dr. Robert Orlowski from MD Anderson Cancer Center, Dr. Faith Davies, and Dr. Gareth Morgan from University of Arkansas Medical Sciences discussed new treatments in development, specifically monoclonal antibodies, proteasome inhibitors and HDAC inhibitors, among many others.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

Jack Aiello:

We have a number of drugs that are listed that are currently in clinical trial. Can you talk about some of those, and which is your favorite?

Dr. Orlowski:

I’m certainly happy to talk about that. I’m not sure we have enough data for me to tell you yet which is my favorite, but we can talk about different classes. Maybe that would be one way that would be helpful. One of the classes that are represented here are antibodies. So the first one on the left, elotuzumab is an antibody.

The first one on the right, daratumumab and then the next one underneath that, SAR650984, is an antibody as well. These are, I think, very exciting drugs, because they are very targeted. It’s an antibody, which I actually think is kind of interesting, because myeloma cells make antibodies. And here what we’re doing is we’re turning that against them by using an antibody.

What these drugs do is they’re usually administered IV, intravenously, and typically they will attach to the surface of the myeloma cell and make it more visible to your immune system and help your immune system to attack it. So it’s a great class of drugs, because they usually don’t have many effects on normal cells, so the side effects are very low.  And patients often worry that other chemotherapy drugs will depress their immune system, but these are drugs that actually help the immune system work better.

The other antibody here is siltuximab down on the left. And although that was studied in myeloma, unfortunately the data with that drug were not positive enough to lead to an approval. But I think the three antibodies I mentioned earlier are showing very exciting results, and I hope that they will be approved over the next couple of years, especially maybe elotuzumab and daratumumab may be approved in 2015.

If it’s okay, I’ll leave some of the other drug classes for my colleagues, but I would like to say one thing about Phase I studies. There are different types of Phase I studies. Some of them are indeed new drugs. You may be the first person ever to get that drug, and you may not know a lot about whether it has a chance of working or not. But we sometimes combine drugs in new ways, and that still has to be a Phase I study.

The one example I’ll give you is we did a trial here, which is still open by the way, where we combined pomalidomide (Pomalyst®) with carfilzomib (Kyprolis®), which are two drugs that we know work against myeloma. But because we were combining them, which hadn’t been done before, it was still a Phase I study. But, in fact, the response rate was something like 80 percent.

So even within the Phase I studies there are different kinds, and that’s where I think talking to your doctor or your nurse or other healthcare provider for the details is important.

Dr. Davies:

So I’ll maybe pick up on a couple of the other drugs. As Dr. Morgan mentioned, we’re now learning that not everybody’s myeloma is exactly the same and that we can actually begin to split myeloma into different kinds of myeloma, and much of this is based on some of the important investigations being done in the lab.

And so the last drug that’s listed on that slide, trametinib (Mekinist®), is actually a drug which has had approval in the melanoma world for the skin cancer world. And what some of the investigations of myeloma showed was that it actually had shared some of the laboratory tests that you can see in melanoma.

And so that is a mutation, which is a change in one of the genes, in melanoma, which is in what they call the endless pathway. We don’t need to be too bothered about the different pathways, but we can actually find that same finding in some myeloma patients.

And so there [have] been some studies now that are ongoing really trying to individualize myeloma patient care, so saying this is the findings we find on particular myeloma patient cells in the lab. Let’s see if we can match the changes of that myeloma cell with a specific drug. So it’s a bit more, I was going to say, tailored and personalizing therapy, and that’s the example at the bottom there.

And I think that’s one of the ways that things will be moving forward is that we’ll maybe in the future be saying, okay, all myeloma patients get this set of drugs, because we know they potentially work. But then we refine the treatment a little bit more and say, but your myeloma has got this specific kind of abnormality, you should also have this drug as well.

Jack Aiello:

Dr. Morgan, can you talk about ixazomib and oprozomib?

Dr. Morgan:

So we used the proteasome inhibitors, doesn’t really trip off the tongue very well. I’m intrigued with the proteasome inhibitor, and Robert here kind of helped find this class of drugs, so we know they’re really effective.

Having them injected intravenously, some of them twice a week, can impact on your life, and so there’s been a big push to develop oral agents that work slightly differently so that you can stay on them, be at home, not be in the hospital for three hours, four hours, to have your infusion.

So oprozomib and ixazomib are two oral proteasome inhibitors that work similarly bortezomib (Velcade®) maybe, with slightly different activities, that you can take as a tablet, and it opens the way for long-term treatment without having to go to a doctor on a weekly basis.

So I think it’s really good because, that sort of duration of exposure; so, long-term exposure of the bad cells to the drugs may be more effective than high doses given at any one time. It’s certainly making them more tolerable for the patients. So I think that’s a great step forward, but in reality they’re in late phase clinical trials.

And so in the next couple of years they’ll become available for patients, the other drugs on there. So we all know about DNA and the mutations and targeting mutations. But there are these things called epigenetic change so that just means the way the DNA is packed.

And so if it’s packed, you can switch off genes, which should be still active but make cancer push forward. So panobinostat and vorinostat unpack the DNA, make certain genes switch on again and make the cancer cells behave better. So these are interesting drugs.

They are effective. They’ve been shown in clinical trials to be effective. They have a side effect profile, which means we need to understand how to use them a little better. So although they’re approved, they come with some need for doctors to learn how to use them appropriately for patients.                  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you. 

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Page last updated on January 6, 2015