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Expert Perspective | How Bispecific Antibody Therapy is Transforming Myeloma Care

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 How has bispecific antibody therapy changed myeloma care? Tiffany Richards, a myeloma nurse practitioner, explains how bispecific antibody therapy works, who this therapy may be right for, and the important role of the care partner when caring for a loved one. 

Tiffany Richards, PhD, APRN-BC, AOCNP is a Nurse Practitioner in the department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center.

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Transcript:

Katherine Banwell:

I’d like to start by learning a bit about you. Can you tell us about your role in the Myeloma Care Team? 

Tiffany Richards:

Yes. So, I’m a nurse practitioner and I’ve been here at MD Anderson for 20 years working with patients with plasma cell dyscrasia. And so, I work in collaboration with our nurse as well as our myeloma physician to not only evaluate patients, what their responses are to treatment but also to make sure that they’re tolerating treatment well, and then adjusting medication or providing supportive medications so that patients are better able to tolerate their therapies.  

Katherine Banwell:

Bispecific antibody therapy is a newer therapy. How has this option changed myeloma care?  

Tiffany Richards:

Between that and CAR T, it’s really offered our patients the opportunity to utilize the body’s own immune system to help fight the myeloma cells. I think the one nice thing that the bispecific antibodies have allowed is that you’ve had a group of patients that maybe weren’t candidates at that time for CAR T either due to other medical conditions or maybe because their disease isn’t at a place where we would be able to get them to CAR T.   

Either maybe their lymphocyte count was low, white blood cells, and so maybe the ability to collect those T cells would be impaired or the disease itself was rapidly progressing and so the patient would not be able to be off therapy in order to have those T cells collected.  

And so, the bispecific antibody allows us to utilize those T cells to go after the myeloma cells without having to go through the process of having to collect those T cells. And so, that has really changed for that group of patients. But also, we have a bispecific antibody therapy that doesn’t target the same receptor that the CAR T-cell therapies do. So, our CAR T-cell therapies target something called BCMA, which stands for B Cell Maturation Antigen.

That’s expressed on the surface of the myeloma cells, and there’s a bispecific that targets a different receptor called GPRC5D. It’s a lot of letters. But it’s a different target, and so even for patients who have had CAR T-cell therapy we can use that bispecific antibody now for those patients who have maybe progressed on CAR T.  And so, it’s allowed another treatment option for patients that they didn’t otherwise have.  

Katherine Banwell:

So, how many bispecific antibody therapies are available for people and how do they differ? 

Tiffany Richards:

So, we have three. So, we have two that target the BCMA; so, that would be teclistamab (Tecvayli) and elranatamab (Elrexfio). And then, we have a third one that targets the GPRC5D which is called talquetamab (Talvey). And so, we utilize the talquetamab if we wanna use a bispecific therapy that does not target the BCMA. And then, for patients who maybe wouldn’t be able to get to CAR T, we might use one of the BCMA therapies.  

And as far as differences between to the two BCMA, really, they’re pretty similar as far as response rates. They haven’t been compared head-to-head. And so, different centers might utilize one versus the other depending on what they have on formulary. So, I would just say, whatever one your center is utilizing that would be the one to go with. 

Katherine Banwell:

Why is a care partner required for patients who are undergoing bispecific antibody therapy?  

Tiffany Richards:

That’s a great question. So, it’s because of some of the side effects that we can see in patients who are undergoing bispecifics. So, similar to CAR T cell therapy, we can see what’s called cytokine release syndrome. We abbreviate that by CRS. And then, we also can see neurotoxicity. We don’t see it to the same degree that we see it with CAR T but patients can still experience it.  

So, cytokine release syndrome, you can get fevers. You can have a drop in the blood pressure, chills, increase in the heart rate. And so, because of that you have to be monitored closely because, if you would start to have cytokine release syndrome, we need to make sure that we’re properly intervening and we can utilize a different medication called tocilizumab (Actemra) to help quiet the immune system a little bit, quiet down those T cells. And so, you need to have somebody that’s with you at all times that knows you, and also, same with the neurotoxicity. Again, we don’t see it to this same degree that we see it with CAR T, but that doesn’t mean that it can’t happen.  

And so, you really need to have that care partner alongside of you. Plus, I think just with these immune therapies, it’s a lot of information that we’re giving patients.   

And so, it’s important to have that other person there to kind of hear what maybe you’re not able to catch. There’s a lot of information that’s being given to you and can be very overwhelming at times. And so, it’s important to have that second person there to kind of be another set of ears as you’re going through this journey. 

Bispecific Antibodies for Myeloma | Patient Eligibility Requirements

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Bispecific Antibodies for Myeloma | Patient Eligibility Requirements from Patient Empowerment Network on Vimeo.

What are the myeloma patient eligibility requirements for bispecific antibodies? Nurse practitioner Alexandra Distaso from Dana-Farber Cancer Institute discusses patient types that work well with bispecific antibody therapy, patient eligibility requirements, and updates about research developments with bispecifics.

Alexandra Distaso, MSN, FNP-BC is on the Multiple Myeloma Nursing Team at Dana-Farber Cancer Institute.

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Transcript:

Katherine:

Well, who is this treatment approach approved for, and what are the eligibility requirements?  

Alexandra:

So, one thing that’s great about bispecific antibodies is that there is not a lot of restriction on who we can use these therapies for. So, these are great for patients who are a little bit more frail or maybe aren’t up for something like a CAR T, or whose disease is a little further along, and they don’t have time to wait for something like CAR T, which requires collecting of cells and manufacturing. What’s great about these medications is that they’re off the shelf. They’re ready to go kind of when you need them. There are restrictions in terms of how many lines of therapy that you need to have had before you can currently get bispecifics.  

So, right now, you need to have four prior lines of therapy, and that needs to include an immunomodulatory agent. So, something like a lenalidomide (Revlimid) or a pomalidomide (Pomalyst), a proteasome inhibitor like bortezomib (Velcade), and a monoclonal antibody like daratumumab (Darzalex) before you’re eligible for these.  

Katherine:

Have there been any recent bispecific antibody research developments that patients should know about?   

Alexandra:

So, there are at least three bispecific antibodies that are hopefully coming into approval in the next several months to year, cevostamab being one of them. It’s a very exciting time for myeloma with all of these medications being approved. Teclistamab (Tecvayli), elranatamab (Elrexfio), and talquetamab (Talvey) in the last year. There’s still a lot of research on bispecific antibodies, especially trying to bring them all outpatient instead of just having inpatient treatment, and in addition, looking at them with other medications, such as teclistamab with daratumumab. 

Evolving Myeloma Treatment Options | Bispecific Antibody Therapy

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Evolving Myeloma Treatment Options | Bispecific Antibody Therapy from Patient Empowerment Network on Vimeo.

What are bispecific antibodies, and how are they advancing myeloma care? Dr. Omar Nadeem of Dana-Farber Cancer Institute discusses the role of this new therapy in myeloma care, shares an update on ongoing bispecific antibody research, and compares this treatment to CAR T-cell therapy.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

Download Resource Guide

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Transcript:

Katherine:

Well, another therapy that has emerged in myeloma is bispecific antibodies. What patient type is this therapy right for? 

Dr. Nadeem:

So, bispecific antibodies are great because they’re off the shelf. What that means is that CAR-T cells, we first have to collect the T cells and we then have to send them off to be manufactured, and that manufacturing process can take up to a month, sometimes even longer, for some of the current available CAR-T products.   

And then, after the cells are returned to the facility, we then give usually three days of chemotherapy to try to suppress some of the immune systems of the patients. So, that way, when the cells are administered, they can expand robustly and do essentially what they need to do. 

So, that whole logistical process can take a couple of months by the time you identify somebody for CAR-T cells and then, from that moment until they can actually be treated. With bispecific antibodies, if we think somebody’s ready to go, you can basically get it as soon as we can have somebody ready to go either in our clinic or on the in-patient facility.

So, they’re much easier. They also utilize T cells to attack myeloma cells. We now have three approved bispecific antibodies. Two of them are targeting BCMA, the same exact target that we have in CAR-T cells, and one of them is now targeting a new target called GPRC5D, which is also highly expressed on myeloma cells.  

So, having all these bispecific antibodies available is excellent because patients can have access to them a lot faster and now we’re trying to answer the question of sequencing. Can you give bispecific antibodies after CAR-T cells for example? Can you give one bispecific antibody after another, especially if there’s a different target that we now have available?  

As a whole, though, bispecific antibodies tend to have lower response rates than CAR-T cells, particularly cilta-cel (Carvykti), which is cilta-cel that has a very high response rate of close to 100 percent.  

Most bispecific antibodies have response rates somewhere around 70 or so percent, so about two-thirds of patients respond to these therapies, again, in that fifth line or four or more lines of therapy. So, in that space, that’s the response rate. And across the board, generally speaking, patients benefit from these bispecific antibodies approximately a year on average. Some of the studies have shown longer benefit, and it also depends somewhat on response to therapy.  

Patients that have a really deep response can go even way longer than that. So, it is quite mixed in terms of how somebody may do on these bispecific antibodies, but those are the numbers.  

Katherine:

Well, it sounds like bispecific antibodies have really transformed myeloma treatment options.  

Dr. Nadeem:

Absolutely, and what goes hand in hand in this.  

I mentioned the logistics of CAR T, but then there’s also the supply and availability of CAR-T cells. Since the approval, the demand for CAR-T cells has been very high because of all these excellent results, but the supply really hasn’t been there. So, even at a center as busy as ours, we can only treat a handful of patients with CAR T-cell therapies compared to bispecific antibodies, where that is essentially an injection similar to many other approved myeloma agents that you can just readily treat patients with. So, CAR-T cells, while I think, again, have higher efficacy, with that comes slightly higher toxicity as well. It’s a very different kind of treatment program.  

And then, patients get a treatment-free interval, which you don’t see yet with bispecific antibodies. On the other hand, bispecific antibodies are readily available, slightly lower response rates, slightly lower toxicity when it comes to at least the traditional T-cell directing toxicities. And then you have, again, the readily available nature of it, which I think is hugely beneficial for patients.  

Katherine:

You talked about some specifics regarding bispecific antibodies, but are there updates in bispecific antibody research that you’d like to share? 

Dr. Nadeem:

Yeah, so, again, kind of following the theme of what we just said about CAR-T cells, can you bring these antibody therapies earlier? And there’s ongoing trials now looking at it in newly diagnosed multiple myeloma and early relapses, and then we presented our data at ASH this previous year looking at it in high-risk smoldering myeloma. We treated patients with teclistimab (Tecvayli), which is a BCMA bispecific antibody that is approved for relapse refractory patients. And what we demonstrated in that study is that people that got teclistimab had a 100 percent response rate with an MRD-negative rate. So, kind of as deep of a response as we can measure, also at 100 percent.  

So, this is something that we had not seen before. When their immune systems are a lot healthier, they may benefit more. So, hopefully we’ll see confirmation of these results in other trials.  

Particularly in the newly diagnosed space because we do think that these antibody therapies have such huge potential to treat patients, and then hopefully we’ll have durable responses. So, I do think that some of this paradigm may shift over the next few years, and then there’s also combinations that are currently being studied: combinations with traditional myeloma therapies, such as monoclonal antibodies, other immunomodulatory agents, or proteasome inhibitors. All these combination trials are now ongoing to see can you improve upon some of those numbers that I highlighted before with single-agent bispecific antibody therapy. 

Katherine:

Can you share the pros and cons of bispecifics and how it compares to CAR T?” 

Dr. Nadeem:

Yeah. I think we mentioned earlier that as a whole, they’re very similar. They’re both T-cell re-directing therapies, in many circumstances, with the same exact target of the myeloma cell, but because this isn’t a cell infusion – this is a cell injection – that you receive that redirects your T cells to the myeloma cells, you tend to see a little bit of a lower toxicity signal when it comes to the cytokine release syndrome incidents and severity. You see lower neurological toxicity, usually, than you do with CAR  T-cell products as a whole.  

With that comes slightly lower efficacy than you see with at least some of our CAR-T products, but if you respond to therapy, then the durability of response can be as good as you can achieve with CAR-T cells. One thing to note about the bispecifics, though, is that it is continuous therapy, so you are getting it on some regular schedule. Right now the approval is for it to be given weekly and then go to every two weeks after six months of therapy if you’re basically in a good response.   

A lot of that is to try to mitigate the risk of infection. So, that is one of the biggest things that we have seen with bispecifics more so than CAR-T cells. Because it is continuous administration of these therapies, that really suppresses your immune system significantly, and infection rates are quite high. So, we typically give other ways to try to mitigate that using immunoglobulin infusions to try to boost up your immune system. Typically, we do that once a month for patients, making sure you’re on the right prophylactic medications and then really adjusting the therapy and the schedule to you depending on your tolerability.  

So, as we said before, it’s an excellent option. I think bispecific antibodies are going to be the mainstay of myeloma therapy going forward because CAR-T cells, again, we can’t really treat everybody with CAR-T cells just simply because of the dynamics of how the process is. So, having the bispecific antibodies available for patients is excellent.