Real-World Management of CRS in Patients With Relapsed/Refractory Multiple Myeloma


Following their review of data from MajesTEC-1, panelists consider how they manage patients with cytokine release syndrome in the real-world setting.


Thomas G. Martin, MD: I’m going to ask you about your clinical practices. Jeremy, how do you treat CRS [cytokine release syndrome] at City of Hope [Phoenix] in Arizona?

Jeremy Larsen, MD: The data are incredibly helpful. They highlight our gut suspicion, but it’s always nice to have data to back up your practice. I echo exactly what you’re saying. I’m a large advocate for jumping right in around that first fever. To use your verbiage of mini CRS, if you have fever light and you’re very borderline, there are instances where we’ll watch those patients for a few hours. If it’s a bona fide true fever, we’ll look at 1 dose of tocilizumab. In our experience—also backed up by this data—that’s often enough to get through the rest without recurrent CRS events. Steroids upfront with first fever isn’t generally part of practice. That’s definitely more post-tocilizumab if they have neurotoxicity concerns or are still febrile after tocilizumab.

Thomas G. Martin, MD: In the event that a patient gets subcutaneous teclistamab, we’ve followed it in the 50 patients we’ve treated at UCSF [University of California, San Francisco]. The earliest onset we’ve had of CRS has been 16 hours. When you give it on day 1, you’re not going to see the CRS until day 2. In that 16- to 48-hour time frame is when you’re seeing that CRS. I tell everybody that CRS occurs only at night because that’s when we need to get called and decide whether to give tocilizumab. Now we have … orders that just say, “Consider tocilizumab with first fever of 38 [degrees Celcius].” How do you guys do it [Winship Cancer Institute] at Emory [University]?

Ajay Nooka, MD, MPH, FACP: Before I start, you probably need to patent mini CRS because it will be used very often. This is a mini CRS. Based on the REMS [Risk Evaluation and Mitigation Strategy] program, every patient needs to be hospitalized for 48 hours after the first step-up dose, second step-up dose, and the target dose. We want to see how we can give this as an outpatient. We want to understand more about the dynamics in the real world. For the first 10 patients, we did exactly what was detailed in the protocol. After the first 10 patients, we went to back the drawing board to figure out the median time from the first step-up dosing to the first CRS event. It’s similar to what you alluded to: 16 hours for you. We got it by the days; it was 2 days. For the next 10 patients, we used prophylactic tocilizumab4 hours before the second dosing. We studied the next 10 patients to see exactly how we’re able to prevent CRS. CRS numbers have gone down drastically, but we had 1grade 3 event that required a hospitalization. We still weren’t there to finally move to an outpatient setting, where it would be more convenient for the patient. We’re still continuing to give the tocilizumab inpatient. As you have said, our threshold for giving tocilizumab is very low. Any time there’s earlier incidence, which usually happens at night, we typically go on with dosing with tocilizumab.

Thomas G. Martin, MD: For the IMWG [International Myeloma Working Group], we have an immunotherapy committee. We have committee meetings, and we’ve talked about this globally with teclistamab. There are definitely different opinions on how to treat CRS with bispecifics. There’s 1 group, as we do at UCSF, who we just go ahead and [use] tocilizumab for after the first fever. Go for it. We have the second group, which maybe Jeremy is more [part of].If the temperature is 38.1°C, give them Tylenol and a dose of dexamethasone. See if that goes away. If it doesn’t and the fever comes back within 24 hours, then give the tocilizumab. Others had said they would use acetaminophen and dexamethasonefor grade 1, and they would use tocilizumabfor grade 2. There are varying opinions on how to do this. There isn’t1right way. Everybody has to develop their practice plan so that everybody in the hospital—the nurses, etc—knows how to treat these patients when they have an episode of CRS. What’s your plan? What are you going to do going forward? Jeremy, have you tried to treat anybody as an outpatient?

Jeremy Larsen, MD: We haven’t. It’s something that’s in the works.Right now it’s more of a practicality limitation. What happens when that nighttime fever comes in overnight, the hospital bed limitations, and not wanting the patient to end up in an ED [emergency department] elsewhere where providers aren’t familiar with it. In the future, that’s where the puck is headed. But we’re still admitting patients by the book. In general, we’re trying to[release them]2 days later, as long as there’s not ongoing CRS, Maybe we’ll look at the 1-, 3-, or 5-day dosing to reduce the duration of the hospital stay for those patients who are doing fine with therapy and not needing CRS interventions.

Thomas G. Martin, MD: How about prophylactic use? We just heard from Dr Nooka that they’ve tried it a little. At ASH [American Society of Hematology Annual Meeting], Suzanne Trudel presented data using a different bispecific, cevostamab, targeting FCRH5.The use of prophylaxis decreased the CRS rates to more than 50%lower if you use prophylaxis. Do you do that at City of Hope?

Jeremy Larsen, MD: We haven’t started to. I’d love to see more prospective data. I’m glad Dr Nooka and other myeloma experts are starting to accumulate these data center by center. That’s 1 of the big things that could move this out even further into the community. We [need to] show that patients aren’t having high-grade CRS [and also] reduce the frequency of this as much as possible. We’re all spoiled being myeloma doctors, and we’re thinking about CRS and these things. If you talk to community practitioners, CRS isn’t something they’re wrestling with daily. As you highlighted before, [we need to] standardize management algorithms as much as possible. I understand why tocilizumab was not in the teclistamab label. Hopefully, over time, the FDA will start to consider these data, because they’re incredibly useful. It’s good for patients. It reduces hospital stays and the severity of CRS. There’s no prophylaxis, but hopefully [there will be] in the future.

Transcript edited for clarity.

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