Where Do Bispecifics Fit in the Multiple Myeloma Treatment Paradigm?


Shared insight on the role bispecifics will play in multiple myeloma management as other novel agents and clinical trials continue to enter the landscape.

Cesar Rodriguez, MD:
Scott, I’m curious to hear your perspective on where you see this treatment in terms of the landscape for treating multiple myeloma. Do you think bispecifics are going to be agents that we use only as boutique drugs in these academic centers or large centers? Or is this is a therapy that can be given in the community as well? Will it eventually be given at the community?

Scott A. Soefje, PharmD, MBA, BCOP, FCCP, FHOPA: You just asked the million-dollar question. When you look at these drugs, particularly the pipeline of bispecifics that are coming, at some point there’s going to have to be a discussion about whether this has to be in a hospital setting. A lot of it is going to depend on the adverse effect profile for that bispecific and how it fits in to the overall picture of what that patient is going to be receiving. We’re still learning how to deal with cytokine release syndrome [CRS]. We’re getting better at it over time. At some point, some of these drugs will be given in the community practice from the beginning all the way forward. It may not be this generation of bispecifics. It may be the second or third generation. We’ll learn how to deal with the cytokine release. We’ll learn how to give supportive meds to prevent or reduce it. Then you end up with those patients in the practice.

The other big question is where [bispecifics] are going to fall in the course of therapy. When you talk about fourth-line therapy, for a lot of institutions, particularly at my institutions, these are competing with clinical trials. If you’re an academic institution and clinical trials are your thing and the market where you want to be, then we have to decide: does this patient go to the standard-of-care drug? Does he go to the clinical trial? How do we decide which is which? They’re also competing head-to-head with CAR [chimeric antigen receptor] T cells. [One question is], where do you do this? Then you start talking about sequencing. Can we sequence BCMA agents? Some early data say that maybe we shouldn’t do that. If we give CAR T first, then maybe we can give the bispecifics later. All of this has to be worked out because we’re so early.

Before we figure out all the BCMA, the rest of the targets are going to come out, and they’re going to fall into this whole picture. You’ve got this massive puzzle, and you’re trying to put it all together. Eventually, we’re going to need to do some clinical trials. I hope the NCI [National Cancer Institute], at some point, starts doing head-to-head trials with different solutions so that we know what to do, where to go, the next step. That’s what it’s going to take to figure out where we’re going, what we’re going to do, and who can do it.

Cesar Rodriguez, MD: You raised a very good issue. It’s a blessing but also a hindrance. We have new agents that are approved, and we can give them to patients who’ve had 4 prior lines of therapy. But it competes with clinical trials. It competes with CAR T. When we were first waiting for approval for these agents to be given commercially, we were all excited. We had a long waiting list of patients who weren’t eligible for clinical trials or, for some reason, wouldn’t be placed in a clinical trial. But we’ve depleted that pool of patients who were waiting for these approvals. Now we’re starting to say, “We still need to prioritize clinical trials.” If a patient is eligible for a clinical trial, not just the standard of care with a bispecific or CAR T, then we offer them clinical trials and give them the opportunity to choose.

At this point we’re using fewer commercial agents because we have clinical trials that might offer something a little better or in combination with something. We’re still trying to learn. Now that these are available, we hope this doesn’t impact the clinical trials that are ongoing and the future clinical trials. As we move these more up front, that can also have a big impact because these agents are achieving great responses. We’re seeing responses that range from the 60th to 99th percentile, depending on what agent you’re using. They’re having a very durable response, making patients relapse much later. What we’re going to offer at that time is a little more complex.

The question was, where do I see the role of this treatment in the myeloma landscape? Right now, it’s for patients who don’t qualify for a clinical trial or aren’t interested in a clinical trial, and who are triple-class exposed and have had more than 4 parlances of therapy. Hopefully that’s going to change pretty soon and we’ll be using this more up front. But we also need to be realistic. At this moment, this is still a boutique drug in the sense that only large institutions—with access to ICU [intensive care unit] care, neurologists, and ID [infectious disease] doctors—should be doing it. At least until the adverse effects are mitigated or we’re out of that window for high-risk CRS or ICANS [immune effector cell-associated neurotoxicity syndrome]. At that point, consider transitioning patients to a community setting. I say this because this agent is given in step-up doses to try to reduce the risk of CRS and neurotoxicity and cytopenias. Unfortunately, up to 70% of patients will still have some degree of CRS and some degrees of other adverse events. This happens normally within the step-up doses.

Transcript edited for clarity.

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