Published on September 29, 2020
What Do Newly Approved Monoclonal Antibodies Mean for Myeloma Patients?
Currently there are four FDA-approved drugs for treating multiple myeloma using monoclonal antibody therapy: daratumumab, isatuximab, elotuzumab, and belantamab mafodotin. What are monoclonal antibody treatments and should you ask your doctor if they are right for you? Can monoclonal antibodies be used in combination with other medications and what results can a patient expect?
Dr. Joshua Richter from Mount Sinai and Patient Power Co-Founder Andrew Schorr discuss the impact of monoclonal antibodies on myeloma patient outcomes, as well as ongoing FDA studies for multiple myeloma using monoclonal antibodies.
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Transcript | Monoclonal Antibodies are Changing Outcomes for Myeloma Patients
Hello, and welcome to Patient Power. I'm Andrew Schorr. We’re visiting once again with Dr. Joshua Richter, myeloma specialist at Mount Sinai in New York. Dr. Richter, welcome back to Patient Power.
Oh, thank you so much for having me, Andrew.
Monoclonal Antibodies: A New Type of Myeloma Drug
Monoclonal antibodies. First of all, for people with myeloma, they are a big deal. They were quite an addition to give people hope and a longer life, right?
Absolutely. Nobody knows this better than a lot of the patients who may be watching, who are familiar with diseases like non-Hodgkin's lymphoma, when the drug Rituxan came out, Rituximab for non-Hodgkin's lymphoma, it changed the paradigm. Whatever regimen was being used, we added Rituxan to that and the outcomes were dramatically better. And we were hoping for our Rituxan in myeloma for many years, and now we have four Rituxan-like drugs and more on the way and they combine really well with some of the therapies we're already using.
The Function of Myeloma Cells in Producing Monoclonal Antibodies
Help us understand, what is a monoclonal antibody? I think of it as, is it like a cruise missile to go after something on the cancer cell?
Yeah. It's actually a really great description. So, every cell in the body has little markers that stick up and we call them CDs or clusters of differentiation. They distinguish one cell from another and there's CD1, 2, 3, there's CD469, but basically when we develop these antibodies, much like our body makes antibodies to fight infection, we can engineer molecules that target these CDs that stick out on cells. So Rituxan targets CD20, and CD20 is on all the lymphocytes. So for myeloma, we look for targets that were on all myeloma cells and the optimal cruise missile, if you would, is a CD that's on the myeloma cell and not on too much else.
FDA Approved Monoclonal Antibodies
We've developed several drugs that target things like CD38 which is on all myeloma cells and we have two drugs now, Daratumumab (Darzalex) and isatuximab (Sarclisa). We have two other targets, one is something called CS1 or SLAMF7. I think it's also called CD269, that's what elotuzumab (Empliciti) targets. And then there's BCMA or B-Cell Maturation Antigen, it's another CD. And that sticks up on all the myeloma cells and allows these targeted drugs to go directly to the cancer.
So, you have four. Are they different? So, how do you, as a doctor decide when to use a monoclonal antibody and which one?
Part of it is what the FDA approvals are. So, the FDA gives us some general guidelines of where in time we ought to use them. For example, daratumumab is approved as a first-line drug, so we have the option of using that when someone's first diagnosed. elotuzumab and isatuximab are currently approved after patients have had at least one therapy. And the more recently approved belantamab (Blenrep) is really for people who've had a lot of the other drugs, so it's a little bit later on.
Exactly when to use each one, very complicated. One of the biggest things we consider is the mechanism of action. So, let's take elotuzumab, for example. The target that it seeks is not just on the cancer cells but on another type of cell, we call natural killers. And these are our own body cells that help fight cancer, and they activate them. So we know that as patients go from upfront to first relapse, to second relapse, their total compliment of NK cells decreases. So, we try to use elotuzumab a little earlier on when there are more robust NK cells that the drug can activate to attack the myeloma.
Drugs Targeting CD38
So, you have the CD38 monoclonal antibodies, daratumumab and isatuximab, isatuximab being newer. Are they the same? Will they be differentiated? Do they have different toxicities? Where do we stand with that? Or are we just learning now?
There's always a lot that we learn prior to approval, but we learn a lot more as we get the drug into our hands in the clinics a little more. The drugs are very similar. They target the same thing. In the lab, if you look head to head, isatuximab is a little more potent than daratumumab. However, in clinical trials so far, hasn't been a ton difference in terms of its efficacy.
In terms of side effects, the intravenous infusion of isatuximab is shorter than the intravenous infusion of daratumumab, and with a little less side effect. However, daratumumab now has the subcutaneous version. Isatuximab doesn't have a subcutaneous version FDA-approved yet, but those trials are ongoing. And then in terms of which one to use when, has to do with the approvals.
So isatuximab is currently only approved in combination with pomalidomide (Pomalyst), and within the next four or five months, we'll have it approved in combination with carfilzomib (Kyprolis), based off of the IKEMA trial. Daratumumab has a lot of approvals. It's approved as a single agent in relapse. It's approved with lenalidomide (Revlimid), with bortezomib (Velcade), with pomalidomide, carfilzomib, and then upfront in combination with Velcade-Thalidomide-Dex and Velcade-Melphalan-Prednisone as well as Revlimid. So daratumumab's got a little more utility at the moment.
But it's been around a lot longer.
It's been around a lot longer. It's been approved for about five years now.
What side effects typically go along with these monoclonal antibodies? Maybe we can talk about the two CD38 ones in particular.
Monoclonal Antibodies and Side Effects
So, the biggest side effect that we know with monoclonal antibodies is something called infusion-related reactions. And even though it's called infusion-related reactions, you can still get them from dara when you get it sub-Q. And basically, within the first one to three doses, this is a foreign protein. The body doesn't recognize it. So, when people get these infusion-related reactions, they can get things like itching, swelling, rashes, even things like trouble breathing or wheezing. So, the nurses will monitor your vital signs very frequently. And the biggest thing I encourage patients to do is if you notice something different for your body, a tickle in the throat, a little itching, let your nursing team know so they can address it appropriately. The other side effects are that CD38 is actually on a few other things besides myeloma cells. It's on some of our other blood cells. So monoclonal antibodies actually lower the blood counts a little bit, so we need to monitor that very closely.
Dr. Richter. So, as we've been talking about monoclonal antibodies, are you excited about where we are and where we could be headed?
Absolutely. It has definitely changed the face of the disease. And, I had this discussion with my team the other day, because we were talking about it. When we all started doing this, we would tell every one of our patients, "Unfortunately, myeloma is not curable."
And what we say now is, we are curing some and we will cure more. And the goal is of course, to cure everyone. But the fact that we're batting around the term cure so much nowadays, we really are able to put people in these incredibly deep remissions, cure some and with precision medicine, we're able to pick the right combinations and really get people outcomes that we couldn't have even expected five or 10 years ago.
Dr. Joshua Richter, thank you so much for joining us from Mount Sinai in New York.
It' a pleasure. Thank you so much Andrew.
Alright. I'm Andrew Schorr, reminding you that knowledge can be the best medicine of all.
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