Addressing Challenges When Implementing Bispecific Antibodies in Diverse Settings

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With as many bispecific antibodies as there are on the market today, many more are expected to become available in the near future, explained Melissa Royero, PharmD, during a presentation at the 2024 Hematology/Oncology Pharmacy Association (HOPA) Annual Conference in Tampa, Florida. However, there are health care centers that have not yet felt comfortable taking the leap and implementing bispecific antibodies in their practice.

“It’s safe to say bispecifics are not going away anytime soon,” Royero, clinical oncology pharmacist at OhioHealth Riverside Methodist Hospital in Columbus, said during the HOPA session. “But there are some considerations when onboarding bispecific antibodies.”

Notably, site of care is a major consideration when onboarding bispecifics. Specifically, Royero explained that there are 6 bispecifics that have recommendations in the package inserts related to the need for patients to be hospitalized when receiving certain doses associated with the highest risk of cytokine release syndrome (CRS). Those therapies include teclistamab-cqyv (Tecvayli; Janssen Biotech, Inc), which is indicated for multiple myeloma (MM); elranatamab-bcmm (Elrexfio; Pfizer Inc) for MM; talquetamab-tgvs (Talvey; Janssen Biotech, Inc) for MM; mosunetuzumab-axgb (Lunsumio; Genentech) for follicular lymphoma; epcoritamab-bysp (Epkinly; Genmab A/S, AbbVie) for diffuse large B-cell lymphoma (DLBCL); and glofitamab-gxbm (Columvi; Genentech) for DLBCL.

“If we use glofitamab-gxbm as an example, we have just a single dose [that requires hospitalization], so that’s step-up dose 1 on cycle 1, day 8, requiring hospitalization per the package insert,” Royero said during the HOPA session. “This would mean the patient would get obinutuzumab [Gazyva; Genentech] as an outpatient. Then a week later, [the patient] would come into the hospital setting for administration [of glofitamab-gxbm] and remain hospitalized for at least 24 hours.”

Royero explained further that if there are no complications from the treatment and the patient tolerated the dose of glofitamab-gxbm, then subsequent doses would be able to be given in the outpatient setting. “But as you can imagine, this is a large burden not [only] on health care systems but [also] the patients themselves when asking them to come into the hospital to receive part of the step-up doses,” Royero said. “It’s no surprise that there are health care centers that have already found ways to safely move these doses recommended to be given in a hospital setting to the outpatient setting.”

One strategy used at certain institutions is additional prophylaxis prior to the step-up doses. For example, although there are not robust data supporting this approach as of yet, tocilizumab (Actemra; Genentech) prophylaxis has been evaluated at several institutions as a strategy. Data presented at the American Society of Clinical Oncology Annual Meeting and the American Society of Hematology Annual Meeting & Exposition in 2023 have shown that there was a reduction in the incidence of CRS when tocilizumab prophylaxis was used, according to Royero.

“[As we get more data], it will be exciting to see how all this pans out and how regularly institutions may utilize additional prophylaxis. Of course, despite our best attempts at preventing CRS [and] other toxicities, they will still happen for patients,” Royero said during the session. “For patients with higher-grade CRS, it’s important that health care centers have the ability to initiate timely management with different therapies, such as corticosteroids, tocilizumab, and other supportive care.”

Additionally, Royero noted that although it is beneficial to follow the suggested timing outlined in the package insert, there may be some variability. For this reason, Royero outlined several scenarios that can occur to illustrate this variability, using the example of talquetamab-tgvs step-up dosing.

“In our first scenario, with weekly dosing for the patient, we’d be coming into a hospital setting for step-up dose 1 and remaining in the hospital through treatment dose 1 plus 48 hours of observation, so this is a minimum of 9 days,” Royero said during the session. “In scenario 2, the patient would receive administration of doses in the outpatient setting but then be hospitalized in between doses for monitoring.”

In scenario 3, Royero explained that the patient would have outpatient administration and monitoring for their weekly dosing schedule. However, with the biweekly dosing schedule, the patient in the fourth scenario would come into a hospital setting to start treatment dose 1 or step-up dose 1 through treatment dose 1 plus 48 hours, but this would require a minimum of 12 days of hospitalization. In scenario 5, the patient would have outpatient administration with monitoring in a hospital setting in between doses.

“In our sixth scenario, the patient, again, would have outpatient administration and monitoring,” Royero said during the session. “As you can see, this is very complex, especially if the health care system utilizes multiples of these scenarios based on patient factors.”

Additionally, Royero noted that a scenario that may work for one patient may not work for another. For this reason, it is critical that institutions develop an algorithm or a communication pathway to minimize the confusion this can generate for both patients and health care teams, Royero explained.

From a medication safety standpoint, there are also many look-alikes that exist in the bispecific antibody world, which Royero noted is important to be aware of when onboarding these agents. Specifically, it may be valuable to implement strategies, including “tall man lettering,” to try to minimize the risk of medication errors at various points in the medication use process, according to Royero.

“Compounding can also be difficult for some of these bispecific antibodies,” Royero said during the session. “With epcoritamab-bysp, for example, due to subcutaneous administration, it’s required to be in a smaller volume. There’s also a wide range of doses from that first step-up dose all the way to the treatment doses. For this reason, there’s 2 concentrations of vials that would be utilized for different doses. Additionally, there are dilutional steps that happen for some of the step-up doses.”

With all these complexities and variations with the same drug and compounding of the various doses used, Royero noted that it’s critical to keep this in mind when putting together medication records. Further, providing additional education to pharmacy staff who may be involved in the compounding process may be beneficial.

Additionally, it’s important to create standardization with observation, labs, and symptom monitoring and reporting. Royero also explained that it’s critical to have an expedited process for hospitalization for patients who do develop toxicities, which can often happen after-hours when the patient’s core team is not present.

“Insurance barriers are also important. Making sure that’s being worked on early in the process, [when] it’s been identified that a bispecific antibody may be appropriate for a patient, [can help ensure] that there isn’t a delay in treatment or financial toxicity for the patient,” Royero said during the session. “From an inpatient implementation standpoint, of course, these are expensive medications. So, keeping in mind strategies to try to minimize that cost [can be beneficial], and these may include restrictions.”

Additionally, from a restriction standpoint, Royero noted that it may be necessary, especially in a larger health care system, to think about restricting administration to certain locations, at least initially, to try to iron out some of the problems that may pop up with these agents.

“Staff training is also key,” Royero said during the session. “I want to call special attention to the consult services, who would be outside of that core group of oncology staff who would be primarily managing the patient. So, involving neurology if the patient were to develop a more severe case of neurotoxicity, thinking about our [intensive care unit (ICU)] teams if the patient required an ICU admission due to the severity of their CRS, and then thinking of those points of entry into the health care system. If the patient were to arrive to an emergency department or an urgent care with some of these toxicities, it’s important that those staff are at least aware that these are up-and-coming and they’ll be seeing more and more patients potentially experiencing toxicities from these agents.”

Reference

Royero M. New flavors: bites in hematologic malignancies. Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2024; April 3-6, 2024; Tampa, FL.