Addressing the Challenges of Implementing Bispecific Antibodies in Health Care Centers

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, clinical oncology pharmacist, OhioHealth Riverside Methodist Hospital, during a presentation at the Hematology/Oncology Pharmacy Association (HOPA) Annual Conference 2024 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 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) for MM; talquetamab-tgvs (Talvey; Janssen Biotech) for MM; mosunetuzumab-axgb (Lunsumio;Genentech) for follicular lymphoma (FL); epcoritamab-bysp (Epkinly;Genmab and 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 one 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 the patient a week later 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.

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“But as you can imagine, this is definitely a large burden, not just on health care systems, but 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. Presented at the American Society of Clinical Oncology Annual Meeting and the American Society of Hematology Annual Meeting and Exposition in 2023, data have shown that there was a reduction in the incidence of CRS when tocilizumab prophylaxis was used, according to Royero.

“It will be exciting to see as we get more data, how all this pans out and how regularly institutions may utilize additional prophylaxis. Of course, despite our best attempts at preventing CRS or 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 do 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 with timing. 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 that this can generate for both patients and health care teams, according to Royero.

From a medication safety standpoint, there are also many lookalikes 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. Then 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 actually 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 of 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 making medication records and recipes. 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. Also, Royero explained that it’s critical to have an expedited process for hospitalization for patients who do develop toxicities, which can oftentimes happen after hours when the patient’s core team is not present.

“Insurance barriers are also important. Making sure that that's being worked on early on in the process at the point in time where 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 very 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 also thinking of those points of entry into the health care system. So, 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; Tampa, Florida; April 3-6, 2024.