Dexamethasone Emerges as a Practical Alternative to Tocilizumab for Low-Grade CRS

New multicenter data are giving oncology pharmacists increased confidence in using dexamethasone in place of tocilizumab (Actemra; Genentech) to manage low-grade cytokine release syndrome (CRS) associated with T-cell–redirecting bispecific antibodies. In this interview at the Hematology/Oncology Pharmacy Association 2026 Annual Conference, Donald Moore, PharmD, BCPS, BCOP, DPLA, FCCP, FASHP, discusses why his team revisited this question with talquetamab (Talvey; Janssen), what the recurrence patterns mean for patient counseling, and how pharmacists can approach escalation from steroids to IL-6 inhibition within modern CRS protocols.

Q: Can you give a brief overview of what prompted your team to look at dexamethasone as an alternative to tocilizumab, and why this question matters practically for oncology pharmacists managing these patients?
Donald Moore, PharmD, BCPS, BCOP, DPLA, FCCP, FASHP: Yeah, so the backstory and how we came to doing the study is kind of the spiritual successor to a study that this group did last year. And so this study that we looked at with dexamethasone versus tocilizumab was a multicenter study that included 7 US academic medical centers. We did one last year that was actually presented at the Hematology/Oncology Pharmacy Association (HOPA) and was subsequently published in Blood Cancer Journal that looked at the same question but with teclistamab (Tecvayli; Janssen).

Seeing in that study that dexamethasone was a very feasible treatment option for low-grade CRS, and that it did not seem to impact response rates between those who received dexamethasone or tocilizumab, nor progression-free survival with teclistamab, really prompted us to go, “Let’s make sure that we see the same thing with one of our other bispecific antibodies.” And so we all came together for the next round of this type of study that we’re looking at. We looked at it with talquetamab.

Q: Recurrent CRS after a subsequent step-up dose was notably higher in the dexamethasone group (50% vs 15%). From a pharmacist’s perspective, how should clinicians counsel patients and set expectations before each step-up dose if dexamethasone was used upfront?
Moore: So with the recurrence rates, certainly we did see a bit of a difference with dexamethasone versus tocilizumab. I think it is important to also recognize that, number one, the CRS that did recur with future step-up doses was not of a higher grade. It was either the same grade or a lower grade. It was also generally responsive to dexamethasone, too. So that is pretty encouraging.

I think the important takeaway from this—what I would really counsel a patient on—is letting them know that CRS is probably not going to be a one-and-done type of adverse event as they go through their step-up doses if we are going to be utilizing pocket dexamethasone, which I think many of us within the study were doing, and now many of our colleagues around the country are also starting to do as well. It is a very cost-effective, easy way to treat low-grade CRS, keep these patients outpatient, and avoid bringing them in for an expensive intravenous infusion if we really do not need to.

It’s a matter of letting them have at home a few doses of pocket dexamethasone and letting them know, “I know you had CRS with the first step-up dose. Just FYI, it could also happen with the second one. You should follow the same steps, because it otherwise resolved with that dose of dexamethasone.”

Q: There’s a theoretical concern that corticosteroids could blunt the antitumor immune response of T-cell redirecting therapies. Did your response-rate data, which showed no significant difference, give your team more confidence in using dexamethasone, or do you still have reservations about routine steroid use?
Moore: I would say it certainly is going to add to the literature to say that we probably do not need to be worrying about this as much as some people may have thought in the very beginning. We saw that with the teclistamab study, where we did not see a difference in overall response rate or depth of response, nor in progression-free survival, with those who received tocilizumab treatment versus dexamethasone as treatment for CRS.

We saw virtually the same thing with talquetamab. We saw again no difference between overall response rates or very good partial response, depth of response or better. We did not really get into progression-free survival because a significant proportion of the patients in the study were receiving it as bridging therapy, and they had a very time-limited window before they were bridged to go to CAR T-cell therapy.

Q: If a pharmacist is helping develop or update a CRS management protocol for talquetamab at their institution today, what would you recommend as the trigger to escalate from dexamethasone to tocilizumab, and how quickly should that decision be made?
Moore: It’s a good question, and I think we probably all do something a little bit different with a lot of our institutional protocols. But I know one thing that we tend to do is that if a patient is having refractory grade 1 CRS and continues to have fevers after several doses of dexamethasone—which could be in the order of about 24 hours—that might be a time to pull the trigger on tocilizumab.

I think certainly also that if a patient does have higher-grade CRS, which is grade 2 or higher, we would have a much lower threshold for giving that patient tocilizumab right away. With the grade 2 aspect of our cohort, it was not really clear what might be the best approach because of a relatively small sample size, but higher-grade events would prompt escalation much more quickly.