Round 2—Can Adverse Event Management in Clinical Practice Support Broader Adoption of Bispecific Antibodies for Late-Line Multiple Myeloma?

Watch Round 3 Here!

Charise Gleason: Alright, so can we effectively manage this in clinical practice? Do we have a broader application of this? I'm going to say yes, the data is showing us that more centers are going to outpatient and hybrid models. Again, beds are tight, and this is based on several publications. You're going to see a trend here: pre-dose education, education of your patient, who to call, when to call, and right where to go. And if you think about that, and are so looking at what to look out for, so this is what the clinical team is doing to get that patient ready, right? Consideration of toci as prophylaxis. Then, your step-up dosing vital signs at triage for CRS, whether you have triage apps doing this, nurses doing this, or you have a place for these patients to go. Escalation of triggers to define upfront so everybody knows what we're looking for and when a patient should contact you.  
Then, after the post step-up dosing maintenance, if the patient has done well, they're going to move to less frequent dosing quicker. We've got what the label tells us, and we have what most of us do in practice. For bispecific antibodies, most of us are going to try to get these patients to every 4-week dosing as soon as possible. Typically, they go at least a couple of weeks before you change that dosing. You're seeing more literature on how people are dosing. This is our plan at Emory. We have patient home monitoring—they just do it themselves. We don't have fancy tools for that. They check their temperature. As I said earlier, every 8 hours they monitor for changes in neurologic function or if they have a fever, as Donna said, we grade 1 CRS fever as standard. But, you can't make that assumption. These patients, this line of therapy, they're very immunocompromised, and they might already have infection issues. So, we still do an infection workup on these patients even though we give them prophylaxis.  

Audience Member: Do you measure IL-6 to differentiate between infectious fever?  

Charise Gleason: We do measure IL-6 when they come in with our labs.  

Donna Catamero: That takes a while to come back.  

Charise Gleason: It does. We don't wait on those results. 

Audience Member: How many doses do you give? 

Charise Gleason: So, we give at our center, we give the one prophylaxis prior to the first step-up dose. If they come into our immediate care center and they have signs of CRS, we give a second dose. As Donna said, you have breakthrough CRS even when giving prophylaxis. Typically, when you give that second dose, that's enough. The majority of our patients are monitored for about 8 hours. If their symptoms resolve, we let them go back home on. If the criteria for admitting our patient were, if they're having persistent grade one even after that second dose of toci, or if they're having greater than that, or neurologic changes, basically CAR T, you're more likely to use that. Correct. And I think that's the important thing, you bring up a good point, right?  

A lot of the things we see with CAR T are what really make some of our community providers hesitant to do this, right? We are here to tell you, and I think all of us would agree, that this needs to be given out in the community, and we're going to talk about that in a bit. I like this, and this is from the University of Washington, and this is a great algorithm to show you a center that went and said, This is how we're going to do it. We know if a patient is coming in from home, we know if a patient is in the clinic, and what to do, who's triaging, and what to work up. Ultimately, if they need to go to the hospital, they don't have a special fancy center, they don't have other tools, they have a good plan in place for their patients.  
I think this is a really nice one to look at, and everybody knows their part and the other pieces. Donna had a discussion earlier, I think, about infections. We know infections are a huge issue for these patients and are ongoing. So, when screening and monitoring these patients, what do their baseline counts look like when they come in? What are their prior infection issues? If this is the person who's been in the hospital three times this year with pneumonia, right? You need to keep that in the back of your mind. How do we vaccinate? How do we make sure these patients, family members, or those with whom they live are vaccinated? So they have that support. We prophylax with an antiviral if they have a history of hepatitis B; we're also going to put entecavir in there. Get a lot of pushback on that. By the way, I don't know about you guys. No. It's just not covered very easily. There are a lot of patients, though, it's surprising to them. ‘How did I get hepatitis B? I didn't have sex.’ But anyhow, we do PJP prophylaxis. We rarely do antibacterials or antifungals, but that is very patient-specific, right? I think you see that a little bit more with CAR T. IV IG or SubQ; they need this, and you're going to see that we're getting away from their level. You need to give this to this population of patients. So, we rarely get pushback from insurance on that one. I don't know about you guys.  

Donna Catamero: It's gotten better.  

Charise Gleason: It's gotten much better, but that starts right up. We started up with it when they went to their actual first dosing after the step-up.   

Donna Catamero: You think once it was made into the NCCN guidelines, it got easier to get the insurance?  

Charise Gleason: I agree. I agree. And I'll say that for prophylactic toci too. All right. So patient education, patient education, and knowing how to escalate. I think again, the University of Washington schema was really good. Here's another one that shows a clinic workflow and escalation. They have the home, the dosing patient gets self-monitoring at home, and then they do an APP telehealth visit with these patients afterwards. So, a great way to keep monitoring your patients. They do it after the next step-up. Then, really, once they're at full dosing, they kind of deescalate that…  

Donna Catamero: Down. My telehealth's been a mess because it reverted back to the pre-COVID. So, Medicare A and B aren't getting covered for telehealth visits as of…  

Charise Gleason: Last week. They're not. But we're all very hopeful that that's going to continue. That's a whole other topic.  

Audience Member: Let also the guidelines be not to go to the ER because all those patients are immediately suppressed, and the worst place to go to is the ER

Donna Catamero: But what do you do at one in the morning?  

Audience Member: One in the morning?  

Donna Catamero: You're arguing my case.  

Audience Member: Well, there's always the hematology department at the hospital. They're usually getting their patients… 

Donna Catamero: But beds, having a bed available at one… 

Audience Member: That might be a problem, but it puts the patients at risk. All hospitals are a Petri dish for all kinds of…  

Charise Gleason: Or come to Emory. We have a 24-hour urgent care for oncology patients. Mayo has a great setup too.  

Audience Member: If it's not a General ER, that's different. But…  

Charise Gleason: No, you have to have a plan. Many centers are going to have to depend on their emergency departments. They just are. If we want this to roll out in the community, they are as…  

Donna Catamero: Well.  

Charise Gleason: I can't remember, Donna, keep going.  

Donna Catamero: I do have an ER story for you, and I can't remember which round I'm going to tell you about it. But the risks, yes, the highest risk for CRS is going to be during the step-up dose, but things that you need to consider. So, ICANS, we say step up dose, but I think Beth, you even shared a story too. I think we've all had one or two patients who have ICANS later on. I always say ICANS can happen at any point. More commonly going to be during step-up, but really can happen at any point. I have seen it four cycles in. So that's something to consider. Infections, I can't say enough about infections and it can happen during the step-up dose. I caution that when someone presents with a fever, not to write it. You have to follow your septic protocols.  

These are oncology patients. I know I always like to say common things happen commonly, but when it comes to infections, I can't say it's automatically CRS. We see infection risk throughout the duration of treatment. Cytopenias. Yes. These patients, remember this is a fifth-line treatment. These patients probably already have lower counts. Even during a step-up dose, these patients can be cytopenic and again with infections on top of that. Then, we see that talquetamab targets GPRC5D. I don't see as many infections, or I should say really severe infections, but there's a lot of off. Is it off tumor, on target side effects? Those oral toxicities and those happen really with the first drop of drug. Even though it's a tiny, tiny dose, patients start having symptoms during that step-up dose. So, what triggers an admission? So, this is using the outpatient workflow even at our institution, where you'll speak more about a hybrid model, but if someone presents with a fever, they're getting admitted. I think a lot of other institutions are trying to do an outpatient model and are admitting those patients. I know Emory, you're keeping them for 12 hours, and if no fever, you send them home. Is that  

Charise Gleason: After? Yeah. After they've had another dose of toci, they're monitored, and if it resolves, they keep them for about 8 hours.  

Donna Catamero: These patient comes in with fever, and maybe this is despite prophylaxis toci, we still have to monitor for hypoxia, hypotension. I don't want this to go from a grade 1 to a grade 2. There are other considerations. We're not always so focused on the fever. Other symptoms of CRS, and remember, CRS symptoms run the gamut. It's not just blood pressure, oxygen level, and temperature. Patients can get sick. Then the hospital, we saw from the Mayo trial that half of those patients on outpatient did end up spending about 3 days in the hospital. So, looking at the adverse events or the toxicities, how do we manage this? So, with CRS ICANS, this is going to really lead to, I would say, temporary holds. We are pretty efficient at managing CRS, where we don't necessarily have to delay the next dose because CRS will resolve ICANS rarely, but this might take a little bit longer to resolve.  
We do see these temporary holds. Same with infections, temporary hold. With bispecifics, we don't dose reduce, so we have to hold, and this is where I see the majority of my dose holds are from infections and cytopenias. I think we can manage quite well with growth factor support. This might be a temporary hold with supportive care. Then, there are the GPRC5D toxicities, so the oral and skin toxicities, and this is usually, I don't think, maybe managed as well in the community, and I feel it leads to higher discontinuation rates. Really understanding how we can manage these toxicities, providing that supportive care so that patients can maintain therapy, so strategies with GPRC5D. The oral symptoms, I think, are the most challenging. I would say in my experience, it is about 100% of patients who report taste disturbances.  

Either they lose some degree of taste or complete loss of taste, which then can lead to weight loss. The quality-of-life factor is huge in these patients. This leads to the discontinuation. We know this drug is very, very effective. 70% of patients respond to this. So how can I manage this? I don't, unfortunately, have a silver bullet, but we can use some supportive care. We have the oral rinses, dexamethasone, nystatin, and saliva substitutes. What I think works best is decreasing the frequency. So, we know that the majority of patients who are going to respond, and of those people who respond, we get them into deep responses. So as soon as I can get at least a 90% reduction, I'm decreasing that frequency. It's not in the label, but what we're doing is, as quickly as we can, we try to move to monthly dose dosing. Some of my patients were on dosing every month, and they're doing quite well. And what we've seen is that patients who've needed prolonged dose holds actually maintain their response. We're still figuring out how to best dose these drugs. With skin symptoms, this is usually self-limiting. It happens in the first month of treatment with the skin. Peeling ammonia, lactate, and heavy barrier creams. We can usually support patients through the nails. It's more aesthetic. This is going to be the duration of treatment. But I've not discontinued therapy due to nail symptoms.