Multiple Myeloma: Optimizing ICANS and CRS Management
Gain insight into strategies for monitoring for ICANS and CRS in myeloma treatment, including inpatient and outpatient administration, tocilizumab, dexamethasone, and impact on patient care.
Transcript:
Sagar Lonial, MD, FACP: I think before we get to the next topic for discussion let’s briefly talk about ICANS [immune effector cell-associated neurotoxicity syndrome] and CRS [cytokine release syndrome]. I think that’s something we all feel pretty comfortable with because we’re used to giving CARs [chimeric antigen receptors] and dealing with it. But as these treatments get moved out beyond the tertiary referral centers, that’s going to be something people have to see more of. Monitoring strategies, those kinds of things, [and] inpatient or outpatient administration. What are you all doing?
Luciano Costa, MD: I think that one important thing to keep in mind for using those drugs for the first time or among the first times is now the CRS is really a concern during the step-up dose and the first target dose…. And as we currently practice and how it’s in the label, that is taking place in the hospital. The reality is the majority of patients will have CRS to some extent. I think the rates are…70% across them all.
…It’s going to be hard to and I think it would be a very bad idea to make choices on therapy based on the rate of CRS, at least those current rates. So you just have to be prepared to deal with it. And I think different centers have adopted different strategies. Ours is very early, the closest to prophylactic without calling it that, use of tocilizumab, sometimes with steroid.… I remember the early days of doing trials of those drugs; there’s all this concern, I’m going to give steroids, I’m going to blunt the reaction, decrease the efficacy, and none of that is the case.
So I think we can be quite liberal during those first few days. And beyond that, when those drugs move to outpatient, I hear that from patients…every week, this is the easiest therapy [they have] ever had. We need to have an infrastructure that can recognize and treat should the odd…case have CRS later on, but [there] should really not be any reason for it, right? It’s a very time-limited problem.
Neurotoxicity,…I think it really is a bit of a cultural heritage here of CAR T[-cell], right? Because we all use the same template to grade and to recognize toxicity. We all are aware of ICANS because of CAR T. The rates have been very low, all less than 10%, and very, very rare cases of grade 3 or anything higher than that. I wonder how much of that is just an old person in the hospital at 2 o’clock in the morning with fever, but somebody gives a…score to do it, you know? So that picture that we have from CAR T of somebody [who]…for 2 days [is] getting high-dose steroid, it just doesn’t happen. It’s extremely rare, right? There are sometimes [patients where] there’s some confusion, a problem with word finding, [who we] usually treat with high-dose steroids, and I find that to be very short and very quickly reversible.
Cesar Rodriguez, MD: I would agree, even in commercial use of bispecifics, the rate of CRS is not increasing, despite the fact that the patients are sicker. We have analyzed the data for MajesTEC-1 and published earlier this year in terms of CRS, the role and the benefit of tocilizumab and/or dexamethasone, and based on those data we have incorporated tocilizumab administration at first sign of fever. We’re not waiting for a grade 2, and that has helped reduce the number of grade 2 or higher CRS in our commercial use. And we are also using dexamethasone if there’s a persistence of fever. We don’t use it right off the bat when we do the tocilizumab. If they do have persistence, we will give the dexamethasone, and we can give the dexamethasone every 8 hours if there’s a need, because they’re still having signs of CRS. But that has been very rare.
Normally the tocilizumab tends to do a very good job at it, and it also helps reduce the risk of a second CRS during the step-up doses when you compare it with those who only [received] dexamethasone. So for community practice, I definitely would suggest using tocilizumab for CRS. You can use plus/minus dexamethasone, but I wouldn’t replace dexamethasone for tocilizumab, if possible, just because it will help reduce the incidence of a second CRS.
But also keep in mind that if somebody is having a fever, we’re treating it for CRS, because that’s very likely what’s happening. But we also need to keep in mind that we need to [do a] work-up for infection and cover these patients for a potential infection until we’ve ruled it out because we don’t want somebody to be getting dexamethasone and then just making an infection completely get out of control.
Luciano Costa, MD: …To that point something that is very important to keep in mind is sometimes we report [those] data [and] we say, well 70% experienced CRS; there’s some nuance that doesn’t come out with those data, which is the fact that as counterintuitive [as] it might sound to someone, even though you’re going up on the dose, the rate of CRS goes down. So if you have a CRS with the first step-up dose, you address that properly with tocilizumab; the second dose is going to be higher, the rate is going to be less; and so forth for the third dose.
And that is very counterintuitive to a bedside nurse. Sometimes we have to go and explain why this person…was “sick yesterday,” and I’m going to do the same thing and by the way, I’m going to double up on it. Right? I think that part, it doesn’t come across; some have done a good job of showing a graph where you actually can see that. It’s uncommon to have an upstaging of CRS, and the frequency overall goes down with subsequent doses.
Transcript is AI-generated and edited for readability.
