Specialists in the field of multiple myeloma discuss bispecific antibodies, with a focus on the MajesTEC-1 study on teclistamab.
Peter Voorhees, MD: Let’s go ahead and move on to the bispecific antibodies. The first one I want to talk about is the one that we alluded to earlier, which is teclistamab, or Tecvayli. This got an accelerated approval from the FDA not that long ago from the MajesTEC-1 study results, which we participated in at Levine Cancer Institute [LCI]. This was a study that looked at teclistamab monotherapy in [patients with] heavily pretreated relapsed/refractory myeloma. The overall response rate was 63%. Most of these patients had very good partial responses and complete responses, with durable responses as well, which led to the approval. Reed, I’m going to go to you. How would you decide whether you would consider a patient for teclistamab vs a BCMA [B-cell maturation antigen]-directed CAR [chimeric antigen receptor] T-cell therapy?
Reed Friend, MD: I think what’s really unique about our institution is the collaboration that we have at Morehead with our plasma cell experts. I have a little bit of a unique situation where I can meet with you all weekly and discuss my patients at Morehead, the main institution, but also at our outreach sites, which makes it helpful to determine when would be the best time to incorporate these drugs. I think the bispecifics are really nice because they’re off the shelf and you don’t have to manufacture these T cells. It’s a little bit easier in terms of logistics. I think we’re using teclistamab at our institution; I haven’t personally, but I’ve seen [patients] in follow-ups…and I think it’s a really great option. I think using it earlier is always better.
Peter Voorhees, MD: Yes. I think your point about off-the-shelf is an incredibly important one. I’ve talked about the logistical difficulties in getting patients to CAR T-cell therapy when they’ve relapsed multiple times and you’re running out of therapies to control their disease. And between delays in time from referral to apheresis, and then from apheresis to actual infusion of the CAR T-cell product, you can run into some significant problems, especially if the disease is progressing at a very rapid rate. So in those instances, an off-the-shelf option can be incredibly powerful. For those patients, teclistamab is probably a better option than a CAR T-cell treatment if you don’t have drugs that you can use to control the disease during the CAR T-cell manufacturing process. And then there are the patients who are frailer and perhaps might not tolerate the cytokine release syndrome [CRS] and the neurologic adverse effects that come with these therapies. It’s important to note that cytokine release syndrome is very common, both with CAR T-cell therapy as well as bispecific antibody therapy, but there tends to be more [cases of] higher-grade cytokine release syndrome with the CAR T-cell products relative to the bispecific antibodies, most of which are grade 2, grade 3, grade 4, and grade 5. CRS is actually very rare with BCMA CAR T-cell therapy. Neurologic adverse effects with bispecific antibodies are significantly reduced relative to CAR T-cell therapy. That’s something that’s important to realize as well. And there’s this interesting phenomenon that we’re seeing less frequently now that we treat neurologic adverse effects of CAR T-cell therapy more aggressively early on. But you know, in the initial CARTITUDE-1 study that we participated in at Levine Cancer Institute, there were a number of patients who had Parkinsonian-like toxicities related to CAR T-cell therapy. And in fact, one of these patients came from our institution. The mechanism remains to be fully defined. This remains to be seen clearly, but there’s the possibility that BCMA may be expressed in the same regions of the brain that are affected by Parkinson [disease]…. That said, I think now that we’re treating neurologic adverse effects early on more aggressively, we’re seeing far less of that issue. But if you had a patient with preexisting neurologic disease, particularly Parkinson [disease], you might gravitate toward a bispecific rather than the CAR T-cell therapy. And we haven’t seen the Parkinson-like effect with the bispecific up to this point.
Kwabena Osei-Boateng, MD: Just a couple of points. Being the only person treating [patients] in Lincolnton, which tends to be more rural, it’s exciting to know that you have these bispecifics because one with them is off the shelf and you can use it a little bit more quickly…. I can see a scenario where if you’re in a community and you don’t have access to CAR T, this is really great that you have the ability to do this.
Peter Voorhees, MD: Yes. [That is] one of the challenges in the smaller practices in particular, but we’d certainly encourage those groups to work with us. You know, there’s the need for step-up dosing for teclistamab. In the prescribing information, there’s a recommendation for patients to be hospitalized for a couple of days after the initial step-up dose, the next step-up dose, and then the first full dose. So typically, providers referring patients, if they’re considering teclistamab, they’re referring them to us first. We will take them on in our inpatient service, and we will treat them with the step-up dosing until they get to their first full dose. Typically, the risk of cytokine release syndrome or neurotoxicity beyond that third dose is next to nothing. At that point, we refer back to the referring provider, whether that’s within the LCI regional sites or even whether that’s beyond LCI. And that’s actually worked out very well. [There are] definitely lots of opportunities for partnership on that front.
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