Managing BCMA/GPRC5D-Associated CRS and ICANS in the Real-World Setting

Depending on a patient’s relative risk for cytokine release syndrome (CRS), prophylactic steroid or tocilizumab (Actemra) use may help prevent CRS in those undergoing treatment with bispecific antibodies for multiple myeloma.

Prior to the 2025 Immune Cell Effector Therapy (ICE-T) Congress, CancerNetwork® hosted a panel discussion encompassing emergent toxicities and access to CAR T-cell therapy and bispecifics. The panel included Prerna Mewawalla, MD, director of apheresis in the Division of Hematology and Cellular Therapy at Allegheny Health Network and associate professor at Drexel University College of Medicine; Shebli Atrash, MD, medical oncologist at Atrium Health Levine Cancer Institute and clinical associate professor at Wake Forest University; and Jeries N.J. Kort, MD, assistant professor of hematologic malignancies and cellular therapeutics at Kansas University Medical Center.

Kort began by explaining that despite most CRS events being lower in severity, among patients characterized as higher risk for CRS complications, such as those who are older or those who may have cardiac comorbidities, the data show that prophylactic use of steroids or tocilizumab may help prevent these events. Additionally, he suggested that early use of tocilizumab may prevent further toxicities that occur during step-up dosing, emphasizing that CRS primarily occurs during step-up dosing.

Mewawalla concurred, adding that prophylactic tocilizumab may help facilitate outpatient treatment for those undergoing bispecific treatment for CRS while moving them back into the community setting. She further pointed out that in the real-world setting, patients are often older with poorer performance statuses and more comorbidities. For these patients, she asserted, early prophylaxis would be particularly helpful in mitigating CRS events and preventing infections.

Atrash contributed by explaining that 2 key differences emerged when comparing the real-world findings with clinical trial data: the criteria used when determining bispecific use and the relative dosing frequency. By looking at the real-world data, he explained that it helped to elucidate the most optimal risk/benefit ratio in bispecific treatment. Atrash concluded by highlighting the benefit of early management with tocilizumab and dexamethasone, which effectively managed CRS symptoms without sacrificing efficacy.

Transcript:

Kort: To answer this question, I will answer it in 2 parts: 1, trying to prevent the toxicities; and 2, early management of the toxicities. For patients who are at high risk for CRS complications—for example, older age, other cardiac comorbidities that we are trying to prevent—there are good enough data now to suggest prophylactic use of either steroids or tocilizumab, even before giving the medicine, [may] prevent and cut that risk. Most of the time, the CRS grade is 1 or 2. It is rare that we see grade 3 or 4, but still, it is inconvenient. For patients who are at risk, if we can prevent them from having a fever or having to be admitted or be monitored for a few days in the hospital, why not? [Because] the data are also showing that it is not affecting the efficacy of the drug, and that is the big question here. If the efficacy is the same, and we can prevent it, we recommend, sometimes, in certain scenarios, to give prophylaxis steroids or tocilizumab.

The second point is treatment, and with CRS, early introduction of tocilizumab showed that it does not just stop the acute event that happens but prevents further toxicities with follow-up dosing. That is why we are trying to incorporate it and treat those toxicities early on, rather than to wait for them to accumulate and get worse throughout the treatment course. We must remember that in all these trials, we saw that the risk of CRS happens with the step-up dosing. It does not happen after that. It is very rare to happen after that.

Mewawalla: I completely agree with it. Prophylactic tocilizumab is also another way to get these patients [to the outpatient setting], even during the step-up dosing, and get these patients to the community by decreasing CRS. The CRS is reduced to less than 15% by using prophylactic tocilizumab. I completely agree with that.

Another difference is, in trials, we always have patients who are younger, with fewer comorbidities, and better performance status. In the real world, we have older patients, patients with poor performance status, [and those with] higher comorbidities. Anything we can do to prevent the CRS that we see with these drugs would go a long way. Again, with bispecifics, I cannot stress enough how infection prevention is such a big part of it because the infection risk just lasts for months, even after a bispecific is stopped. Using the right preventative strategies––prophylactic IVIG, antibacterials, antivirals––in a timely manner and treating infection right away as soon as there is a sign of infection is [quite] important in these patients.

Atrash: In regard of the real-world vs clinical trial data, what’s the difference that we have seen? It’s [quite] interesting. We worked with multiple hospitals as a group of physicians, where we looped our data together. [What] you can tell from the first look of it is: 1, each hospital has slightly different criteria for selecting patients into bispecifics vs different modalities; [and 2], the scheduling of the treatment. Whether it’s BCMA or GPRC5D, do you give it every week? Do you give it every 2 weeks? When do you move to every 2 weeks? Or when do you move to [a monthly dosing schedule]? Some of us are giving it every other month. The variety of scheduling [is something] you see [significantly] more [often] in real-world data than you see it with clinical trial data, as everything is regimented. This variation in dosing helped us to [ask], “Do we have more toxicity if we give it weekly vs if we give it every other week or if we give it every other month?”

Also, the question about efficacy: “Are we having a less efficacious approach if we get the treatment every 2 weeks or every month vs continuing every week?” One of the things that we learned is with the management of the toxicity, as Kort mentioned, this early management with tocilizumab and dexamethasone, helped with avoiding long-term problems, but it also did not seem to affect the efficacy of the treatment. It seemed easy to manage the CRS symptoms, especially in the startup dosing, and we did not see big problems, even in the real-world data, with the management of the CRS.