Pharmacists Prepare for Bispecific T-Cell Engagers: What Sets Their Toxicity Profile Apart

Bispecific T-cell engagers (BTCEs) are rapidly expanding into both academic and community oncology settings, bringing a toxicity profile that differs sharply from traditional therapies. While cytokine release syndrome (CRS) and neurotoxicity remain the most visible risks, pharmacists are increasingly responsible for recognizing subtler adverse events, coordinating early intervention, and supporting outpatient monitoring. In this conversation, Megan May, PharmD, BCOP, FHOPA, FAPO, and Emilie Aschenbrenner, PharmD, BCOP, share firsthand insights on implementing BTCEs safely, educating patients and caregivers, and adapting workflows to meet the demands of this evolving drug class.

Q: For pharmacists who are just starting to encounter BTCEs in their practice, how would you characterize the adverse-event profile that distinguishes this drug class from other oncology therapies they may already be familiar with?

Megan May, PharmD, BCOP, FHOPA, FAPO: So for my institution, we're a large community hospital, and we had never given CAR T cells before or anything like this. So for us, it was a big, scary unknown. But with a lot of education, we were able to learn more about CRS and ICANS, which are the two big black box warnings that we look for with these bispecific T-cell engagers. I think with enough education and enough resources laid out, anybody can do it. You just have to prepare as best as you can for these unique side effects that we don't really see with the other agents that we use in the community right now.

Emilie Aschenbrenner, PharmD, BCOP: I don't have too much to add to that. From Megan's perspective, as we implemented these from our academic to our community sites, again, that was a little bit scary. We are a center that does bone marrow transplant and offers immune effector cell therapies or CAR T-cell therapy. So I think for us, this is a little bit different. The timeline is a little bit different. Usually, the rates and grades are different. We’ll get into a little bit more of that background, but really highlighting the differences and that this is really an upfront mitigation strategy with toxicity management, and it doesn't necessarily carry the same risk as we move forward with maintenance dosing.

Q: Cytokine release syndrome and neurotoxicity are the headline toxicities, but what are some of the more underappreciated or underreported adverse events that pharmacists need to have on their radar?

Aschenbrenner: I can start with that. In our presentation that will be upcoming today, I'll lead the section on immunosuppression and infections. We definitely see that a lot in our malignant heme population. And I know that Megan takes care of a lot of patients with lung cancer and tarlatamab, so there certainly is a difference. Knowing that, we need to watch patients closely, follow their blood counts even back into the community setting, and treat them appropriately with antimicrobials. There is a lot more evidence with immunoglobulin replacement, especially in our multiple myeloma population. I don't know if, Megan, you want to comment on some of the other unique toxicities with the agents. One of our presenters, our lead presenter, will hone in on some of those as well.

May: Yeah, one thing that sticks out to me is that with tarlatamab for extensive-stage small cell lung cancer, we do see a lot of dysgeusia. Helping patients overcome that unique side effect and learning different tips—for example, I've learned that if they smell cloves, it might help, or having more peppermint, or rinsing your mouth with bland rinses with salt and baking soda before you eat can help get that taste back for patients. So there are some side effects we don't typically think of. We always think of CRS and ICANS, the big ones up front, but there are some longer-term toxicities we need to be thinking about as well when we use these agents. Yeah, for sure.

Q: Walk us through how your institution approaches the monitoring and mitigation of toxicities. What does that look like practically, from the moment a patient receives their first dose?

Aschenbrenner: We are certainly trying to default more to outpatient infusion sites as the standard of care, although we do admit a fair number of patients, either through step-up dosing or at least for observation, like with tarlatamab. Ideally, if we're able to treat them and they have a caregiver identified—which is the key step in the process—through the outpatient step-up pathways and subsequent maintenance dosing, for step-up at least, they will be followed for two days after. At a lot of sites, they’ll leverage their APPs or pharmacists to call the patient.

We are leveraging our clinic, our nurse, and our clinical nurse specialist. They will ideally do an in-person visit the day after and then the following day—so day two and day three after each step-up dose. If we're not able to do that, we will leverage our virtual visits. If we're not able to do that, that's when we do the phone call. We are able to follow through at our centers and have a pathway to perform this even on the weekend, even if it's not an in-person visit, so those patients are followed up appropriately.

We’re going to discuss in our presentation today some of the strategies health systems that are not integrated are using, like remote monitoring. We have had some high-level discussions about that—measuring, for example, blood pressure at home—but right now, we are an institution that's just doing routine temperature tracking with a thermometer and having the patients call in for any fluctuations.

May: One thing to add: we aren't doing official remote monitoring, but I do provide patients now with a blood pressure cuff, a pulse ox, and a thermometer and allow them to take their measurements at home. You can get free boxes from some organizations, no matter which bispecific T-cell engager you're using, and you can hand them to your patients. I also make sure they have a very detailed list of what to look for and a log to monitor it: when to call us and the number to call us. So we’re really educating the patient and the caregiver on how to monitor these at home. Because we're doing something very similar—we’re trying to move these bispecific T-cell engagers to an outpatient setting—so we really need to rely on the patients as well to monitor at home.

Aschenbrenner: Yeah, for sure. We can leverage some of the tools that our manufacturers or pharma partners give us. We have chosen to have our own handouts at Freighter to MCW that will employ some of those tools. For example, they can have an electronic link or a barcode scanned to a wallet card to carry with them if they don't carry the actual wallet card. Then we’ll incorporate, to Megan’s point, when to call—the who, the what, the whens—the very important points, and just the general layout of what to expect for dosing and side effects. So it’s customized education while still leveraging tools from national organizations like HOPA and CODA, ACCP, etc.

May: One other thing that I like to tell my patients during education is: when you call in, tell the provider, “I'm on a bispecific T-cell engager. I got it yesterday, and I have a fever.” So if you call in the middle of the night, it triggers the oncologist: “Okay, this is not a typical fever. What do I need to do, and how do I act quickly?” So we’re really trying to empower the patients to make sure they get the appropriate interventions they need quickly.