Bispecific Treatment Options for RRMM


Key opinion leaders dive into the use of bispecific treatment options for RRMM.

Jeffrey Matous, MD: Let’s switch gears here and move on from CAR [chimeric antigen receptor] T cells to what I call the T-cell redirecting antibodies or bispecifics. I prefer T-cell redirecting antibodies because we have trispecifics and we have different specifics out there. But at any rate, we’ll call them whatever you want to call them right now. We had the FDA approval; we had the New England Journal of Medicine paper last October with teclistamab based on the MajesTEC-1 trial. Teclistamab is out there. This is the first of many of these products. I should say the same thing for the CAR T-cell products that are going to come out. I think this year we’ll probably have some other bispecific antibodies approved. In the future definitely we’ll have many of these antibodies out there, the same with CAR T-cell therapy. Let’s talk about teclistamab therapy and how it got approved and what it does and that kind of stuff. Do you want to start us off on that?

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Absolutely. As you mentioned, the data that came out of the MajesTEC-1 trial, these patients had a very good response rate. In the trial, the median number of prior lines of therapy was about 5 if I’m not mistaken. Some of these could have gone up all the way to 14 lines of therapy. The approval is, again, based on 4 prior lines and again your IMiDs [immunomodulatory drugs], your PIs [proteasome inhibitors], your CD38 inhibitors.

The interesting thing about teclistamab is some of the operational considerations. No. 1, teclistamab has a pretty big burden in terms of administration, which is not something we haven’t seen in myeloma. Your bortezomib is given weekly, we were very familiar with that. Teclistamab is very similar, we’re giving it weekly. But there’s this ramp-up phase. We still have the concerns for CRS [cytokine release syndrome], ICANS [immune effector cell-associated neurotoxicity syndrome]. I would say from my experience that the risk of CRS and some of those ICANS we see with teclistamab are not as high, or the incidence is not as prevalent as some of our CAR T-cell therapy. There’s a big school of thought of trying to completely keep teclistamab or some of these bispecifics in the outpatient setting.

Beth Faiman, PhD, APN-BC, CM: No, you can’t.

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Ultimately with teclistamab, when you look at it, you have this ramp-up dosing. You start with a baby dose on days 1, 4, 7. Then you start on a weekly dosing strategy. They recommend that those first 3 doses be done in an inpatient hospital unit. You look at the Mayo Clinic, for example, they do it in an inpatient-based unit, but it’s outpatient billing. The patient comes in, they get that administration, they pretty much stay across the street or within a certain radius, as long as they can come back and report any issues. We haven’t had much guidance around how you manage that CRS, for example, from the pharmaceutical partner. You look at the PI [package information], the word.

Beth Faiman, PhD, APN-BC, CM: It’s not in there.

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: Not at all, tocilizumab is not in there at all. Fortunately, Mayo updated their mSMART [Stratification for Myeloma and Risk-Adapted Therapy] guidelines and finally said, “Hey, this is what you should do for this kind of CRS.” That was something I think was very helpful to the clinicians. At least on my side of the world, I’m in the community setting, we wanted to make sure we still provide access to teclistamab for our patients. Fortunately, this wasn’t as cumbersome or as complex as CAR T-cell therapy. We were able to, again, partner with the institutions that have hospital-based units and develop that referring physician, establish that ramp-up dosing schedule within the hospital. Then when it’s time to switch back to the community, you can safely come back to us. We’ve successfully done that across our site.

One thing to always be cognizant of, there’s obviously a need for staff education because of teclistamab. If you have to hold, for example, one known thing with teclistamab, if you look at the rates of grade 3 or 4 infections, they’re much higher than what we would like to see. So, if you have to hold your patient for 28 days, let’s say, for an infection or for whatever AE [adverse event] that may manifest, you’re re-ramping that patient up. Again, there’s that other logistical barrier, do you send them back to the Mayo Clinic or the University of Minnesota, or these kinds of things that we’re doing. These are all things we’ve started to work our way through.

I know you mentioned something about tocilizumab. We don’t always like to pull the trigger on it because of obviously the cost and whatnot. Also in the community setting, we only administer cancer drugs at our institution, we don’t give specialty infusions. If I order tocilizumab, I will not use it for rheumatoid or any nononcologic indication. So, we elected not to stock tocilizumab because, again, we’re doing the maintenance portion of it. Because when you also look at the CRS, the median onset of the CRS was 2 days, or on day 2. So that patient is not sitting in that chair, and you need to intervene.

What we’re probably going to do, if that patient does call us and they are having symptoms of CRS or ICANS, we refer them to an emergency department. We do know that the health systems with emergency departments do have it because they have outpatient specialty infusions as well. Those were some of the barriers and some of the things for how we operationalize teclistamab.

Jeffrey Matous, MD: We’re going to drill down on how to implement teclistamab more broadly than in the academic centers. That’s going to be a really important part of our discussion in a few minutes. But does somebody want to tackle how these T-cell redirecting antibodies work? How do we describe them to patients, and how the adverse effects may be similar or differ from CAR T-cell therapy?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: Beth, do you want to go through that? I’ll go through the adverse effects.

Beth Faiman, PhD, APN-BC, CM: Yes. Again, this is a BCMA [B-cell maturation antigen]-directed therapy, as we already heard in a prior session. B-cell maturation antigen is expressed on the mostly cancerous plasma cells and less expressed in the healthy tissues. It’s a very favorable target because we know that almost all patients with myeloma at some point or another have BCMA. In the earlier studies, they used to do bone marrow biopsies, and if they had BCMA expression, then they’d be a candidate for CAR T or bispecific therapies. And now we don’t even do bone marrow biopsies anymore, we just assume that it’s there and hope that it works.

When you have somebody who wants to go on a BCMA therapy, I talk about how it’s expressed on the plasma cell, and then we have the CD3 linker that brings them together like a helping hand, and the cells die. I almost equate it in my mind to a tumor lysis syndrome from other cancers where the cells are just exploding. We can mitigate the CRS or cytokine release syndrome. As we mentioned, tocilizumab is an IL [interleukin]-6 drug that is not cheap. But when we have our patients who are admitted for 7 to 9 days, it’s usually closer to 9 days at my institution [Cleveland Clinic in Ohio] because the REMS, the Risk Evaluation Mitigation Strategy, says they have to be hospitalized for 48 hours, according to the NCCN [National Comprehensive Cancer Network].

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA: Technically they should.

Beth Faiman, PhD, APN-BC, CM: TheNCCN guidelines have a template for community hospitals. So, the hospital outpatient that Kirollos mentioned, and I think in Utah and some other institutions, they have it where it’s fully staffed, but it’s considered outpatient. But at any rate, it’s very well tolerated if you get that fever first. But if you get somebody who’s had a lot of prior therapies, their blood counts are low, they’re neutropenic, we have to give them a growth factor called G-CSF [granulocyte colony-stimulating factor], you need insurance approvals at each of these stages. So, probably one of the reasons Dr Hanna doesn’t stock tocilizumab is because it’s a pain in the neck to get it approved in case they get CRS in the hospital, and then you have to get it reapproved again in the outpatient area.

What we do is we give it with dexamethasone. We worry about with CAR T cells giving dexamethasone based on the lymphoma literature, but with the teclistamab, we do give dexamethasone if they have CRS, with our tocilizumab. And after that third dose when they’re outpatient, I say, “Do you have any steroids at home? If you get a fever and you don’t feel well, take some steroids,” because at that point it’s less likely to be more severe. I’ve only had 1 person out of 35 who we’ve treated since it’s been approved in October of 2022 who has had to take it at home. It’s a low incidence of CRS as an outpatient. That communication, that is a perfect model you shared with us, Dr Hanna, about having the community partnering with the larger hospital systems, and that clear communication. That’s going to be critical moving forward with these new drugs.

Kirollos Hanna, PharmD, BCPS, BCOP, FACCC: That incidence specifically goes down to 3% of CRS in that maintenance phase. So, it’s extremely low.

Transcript edited for clarity.

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