Round 1—Can Step-Up Dosing and Adverse Event (AE) Prophylaxis Safely Expand Bispecific Antibody Therapy in Late-Line Multiple Myeloma?

Watch Round 2 Here!

Beth Faiman: We're going to have these ladies argue. Can step-up dosing in AE prophylaxis safely expand the clinical use of bispecific antibodies? I don't know. Tell me, what do you think? 

Charise Gleason: Yes, I mean, I have the pleasure of getting to tell you how we should do this in the outpatient setting, how we can do it in hybrid bridge sessions, that we do not have to admit all of these patients to do bispecifics, nor do we have the bed capacity to do that. CRS is very predictable in these bispecifics, so we know when it's going to happen. We give tocilizumab, which has a really long half-life. I'm sorry, our pointer's falling apart there—there we go. If you look at CRS in step-up dosing prophylaxis, I work at a center where we give prophylaxis with tocilizumab. I'm going to show you some of our data, but this is the data from the MAJESTIC trial that 72% of patients had an incidence of CRS. However, when they went back and gave prophylactic toci, you can see that the rate dropped down to 25. 

Then, in real-world experience, you've got Mayo Clinic and the Tech Pioneer study. You can see their data at 11% to 26%. Then, in a newer study with Optech, the interim data are really low. So you can really make a difference if you put tocilizumab in there. Now, everybody doesn't want to do that, but I can say that even if your center chooses not to do that, you can still do these in the outpatient setting. You just have to have a system in place. So this is our experience at Winship Cancer at Emory, and our clinical pharmacist has led this charge. She put together our protocols. She's pulled together our data, and she published it in 2024. We have a unique center, an urgent care called our immediate care center for oncology patients. That's 24/7. So we're able to utilize that. 

Donna may tell you that everybody doesn't get these fancy centers. You don't have to have that, right? You don't have to have fancy tools that monitor temperatures and things, and you don't have to have immediate care to have that. But you do need a good plan in place. Now I happen to have an immediate care center. So our criteria is one is your selection of your patient. There are still patients who need to go to an inpatient, right? It goes back to that performance status. You're going to see this in all the models we talk about today. It's still going to come down to that patient selection. Our patients need to be close by. They need to have 24-hour care support, and they are going to monitor their temperatures every 8 hours after step-up dosing. We don't have them wake up to do it. 

At the first sign of CRS or other symptoms, they're going to call in. They're going to take their prophylactic drugs that we give them—dexin, acetaminophen—and then they come into our ICC. You can see we started with 52 patients receiving outpatient, step-up dosing, and 48 completed it in the outpatient setting. We did have some breakthrough CRS, for which we gave an additional dose of tocilizumab and low numbers of ICANS. Quite honestly, a few of those were questionable, but it's still a part of our data set. We really don't see neurotoxicity much with bispecific antibodies. You can see that the majority of those issues were resolved with supportive care. So, the required admissions were around 7%. We'll have more about this, but I am for prophylaxis, and I'm definitely for doing this in the outpatient setting. 

Beth Faiman: I have for you patient selection, all institutions, when they started the bispecific, it was admission. But then there is a learning curve, there is confidence, there are precautions, there are biomarkers, and you feel comfortable with which patient to be admitted, which patient to be an outpatient, and what to tell the patient when to come, et cetera. So is it patient selection or both? Maybe 

Charise Gleason: It's a little of all of that, right? So, for patient selection from a, can you do this? Outpatient is really about that performance status, or do they not have a caregiver? And there are several slides that are going to show you how we've done it and how other institutions are doing it, and even Donna's, showing you how important patient selection is. And also, sometimes it's the choice of the clinician, and we just have some patients who absolutely do not want to do this, right? In the outpatient setting. I think that at academic centers, we did this on clinical trials; everybody was in the hospital for that, but we got so comfortable with it, as did our staff. And so I think what you need to do this is to really have protocols in place. And we've got some slides we're going to show you, or the organizations, on how they're doing it as well. 

Beth Faiman: Don't give away all the presentation yet. 

Charise Gleason: It's coming. It's coming. 

Donna Catamero: So maybe I'm the bad news bear, but within reason, guys. Right. So, just to level set the MAJESTIC trial, again, the majority of patients did have CRS. 72% of patients had CRS. And I think what's actually more concerning is the recurrence of CRS, granted that these patients, toci wasn't mandated in the protocol. We did see higher rates of subsequent. A third of patients had subsequent CRS, and those are the patients I'm actually worried about. Prophylactic to CRS, yes, I think it's a game changer. Now with the updated NCCN guidelines more readily available, but there is that small patient population I'm worried about, even if I give prophylactic toci, there is some breakthrough CRS that I'm worried about. 
Here is hospital utilization; this is actually the Mayo data, which I think this data has limitations. They had a very low CRS rate. It was around 30% and mainly grade one, so fever. But if you look at the right-hand side of the screen, over half of those patients end up in the hospital with a hospital admission. I will say that when I did look at this trial, I felt like these patients were a little cherry-picked. So, in real-world data, who you're selecting, I think, there is a selection bias. And again, this really speaks to, it's not for everybody. Even with the outpatient, half of those patients ended up with at least a 3-day admission once they had CRS. 

And then this is if you heard my prior talk, infections, infections, infections. So I think CRS, we are good at managing, but infections, the burden is still high. Even with this real-world data, we learned a lot from the trials. We are doing a lot of prophylactic measures to try to prevent infections, but we still see infections, and we even see those high-grade infections, and we can see these infections even during step-up dosing. So, a patient presents with a fever, we can't automatically assume it's CRS, give them Dex and make an infection worse. So that's what I worry about.