Management of CRS in MajesTEC-1: Role of Tocilizumab in RRMM
Key opinion leaders Thomas Martin, MD; Ajay Nooka, MD; and Jeremy Larsen, MD, reflect on the use of tocilizumab in patients experiencing cytokine release syndrome on MajesTEC-1.
Transcript:
Thomas G. Martin, MD: We have more data we’re going to share. How about management of CRS [cytokine release syndrome]? Ajay, do you want to go over the study and what we looked at for management?
Ajay Nooka, MD, MPH, FACP: Absolutely. From a management perspective, tocilizumab is a readily available IL-6 antagonist that we have to treat CRS [cytokine release syndrome]. We saw that 50% of patients had grade 1 CRS and 21% had grade 2 CRS. We want to use tocilizumab based on the ASTCT [American Society for Transplantation and Cellular Therapy] guidelines, where patients who have grade 2 or higher would be receiving the IL-6 antibody. If you look at what you see here in terms of the tocilizumab use, instead of the 21% that you expect, more than 36% of patients received the tocilizumab. Why did that happen? We started to see that if you give the tocilizumab early in the course of the CRS, you’re able to prevent further propagation into a more severe CRS. This is a learning curve for us.
We started to use more of tocilizumab earlier in the course, so the recurrence event of a CRS has significantly declined. Looking at all 165 patients, if 36.4% of the patients received tocilizumab, these are patients who had a recurrent event that was significantly different in terms of patients who had CRS but didn’t receive tocilizumab. 14 patients were treated with steroids, and other patients had supportive care measures with low-flow oxygen with nasal cannula and IV [intravenous] fluids. All the supportive care measures were given. For patients treated with tocilizumab, they’ve received 1 dose, and 6 patients received tocilizumab for more than 1 CRS event. In terms of the steroids, 9 patients were treated with dexamethasone alone for CRS. Of these, 7 had subsequent CRS after the treatment with dexamethasone alone. In summary, of the 119patients who experienced a CRS, accounting for 72%of all patients enrolled in the trial, 55 developed more than 1 CRS event.
Thomas G. Martin, MD: Jeremy, how about a little more on this in terms of the management by grade in tocilizumab as shown on the slide?
Jeremy Larsen, MD: When we break this down into 2 categories of patients—those who received tocilizumab vs those who didn’t—a story emerges that can inform our clinical practice. As we start to usher in bispecifics, this tells us that early intervention iswhere we need to focus. When we look at subsequent CRS events, of the 68 patients who received tocilizumab, 19% of patients still had a subsequent CRS event. We’ll break that down into severity below, but half of patients [had a CRS event without tocilizumab]. That’s a dramatic reduction. What’s incredibly informative is that if I highlight the grade 2 or higher CRS events, of those patients receiving tocilizumab for those subsequent CRS events of any grade, 24% [received tocilizumab] vs 40% [who did not]. We’re preventing grade 1 events but also significantly reducing the number of grade 2 CRS events. If you look at all comers, this suggests that patients with more severe CRS were more likely to receive tocilizumab if you look at the breakdown of patients who received this. The real takeaway is that I can think of the rule of 20% vs 50%. As Dr Nooka pointed out, we can that patients who had intervention earlier were much less likely to develop severe CRS later in their course.
Thomas G. Martin, MD: [We need to] be more aggressive than what’s laid out in the ASTCT for tocilizumab with grade 2. We’ll all use tocilizumab if they have grade 2 or higher. No doubt about it. But the big question is, will you use it in grade 1? We’ll talk more about your clinical practicesin a minute, now that teclistamab is approved.
What we concluded from our journal article [in Future Oncology] was that most CRS events occurring during step-up doses from teclistamab in the MajesTEC-1 were grade 1—50%—with some grade 2s. They were all essentially in that first week that patients were hospitalized for dosing. Clinically, we need to be aware of CRS, especially during the initiation of tocilizumab during that first week,but we can’t forget about it after that first week. Once they go home, they still might have fevers. That’s something we need to ask them each time they come in. “Have you had fevers?”Tell them, “If you have a fever, you need to call in and tell us about the fever,” because maybe we want to start something as an outpatient for them.
The data support management of CRS with tocilizumab. This manuscript was an important defining manuscript for an advocate for the use of tocilizumab. In our clinical practice, we use tocilizumab for first fever. [At the] first onset of grade 1, we give tocilizumab in the hope that it will decrease the risk of having a subsequent fever. These are older patients, sometimes with multiple days of fever. They can start to have delirium. They can start to get a little confused. You’re worried. Is it infection? Is it not infection? We like to jump in and do it. Opinions vary, and it’s different from place to place. As we concluded in the article, patients treated with tocilizumab appear to have less frequent subsequent CRS events.
Transcript edited for clarity.
