What It Takes to Move Bispecific Step-Up Dosing Into the Outpatient Setting

As bispecific T-cell engager therapies move into earlier treatment settings and become available to more patients, oncology practices are increasingly exploring whether step-up dosing can be administered safely outside the hospital. Although outpatient administration may reduce pressure on hospital capacity and improve convenience for patients, it requires careful patient selection, multidisciplinary coordination, clear escalation pathways, and access to supportive medications.

In an interview with Pharmacy Times, Manale Maksour, PharmD, BCOP, BCPS, associate director of Pharmacy Services at American Oncology Network, discussed the growing use of outpatient bispecific step-up dosing, operational barriers to implementation, management of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), payer challenges involving tocilizumab, and the importance of patient and caregiver education.

Pharmacy Times: What factors are driving the growing use of outpatient step-up dosing for bispecific T-cell engager therapies, and which patients may be the best candidates for this approach?

Manale Maksour, PharmD, BCOP, BCPS: There is a major shift from administering treatment in the hospital to administering it in the outpatient setting. First, it is becoming more difficult to find hospital beds for patients who may need to remain there for multiple days during treatment. Outpatient administration can also be more convenient for patients. They typically do better when they are in their home environment rather than in the hospital.

We have also gained more experience with bispecific therapies, so care teams are becoming more comfortable administering them in the outpatient setting. That said, outpatient treatment is not appropriate for everyone, and patient selection is crucial.

Patients should have good cognitive function and should not have a significant number of comorbidities because treatment can be difficult on the body, and they need to be able to tolerate it. They must also agree to and understand the outpatient process. They need to know that they will be going home, monitoring themselves, and calling the care team if they feel unwell or require medical attention.

Most importantly, patients need a caregiver who can remain with them 24 hours a day during the first few days. The caregiver must also understand the treatment, know what symptoms to monitor, and know whom to call if a problem occurs.

Pharmacy Times: What are the most significant operational barriers health systems and oncology clinics face when establishing outpatient bispecific therapy programs?

Maksour: It is a complex treatment and not a straightforward process. It requires a multidisciplinary approach, with many different people involved and a significant amount of education.

Everyone must understand what bispecific therapies are, how they work, what should be monitored, and which symptoms may indicate a complication. Hospitals can also present a major operational barrier because they need to be involved and prepared.

Many emergency departments have not previously managed CRS or ICANS, so their teams must understand what these toxicities are and how to respond. Even when the treatment is administered entirely in the outpatient setting, a hospital needs to be available in case the patient requires admission.

Another barrier involves payers and access to tocilizumab, which may be used for the prevention or treatment of CRS. Practices can sometimes encounter difficulties obtaining approval, particularly when the medication is being used prophylactically.

Pharmacy Times: What infrastructure, staffing, and coordination are necessary to safely operationalize outpatient step-up dosing across pharmacy, nursing, physicians, emergency departments, and other members of the care team?

Maksour: It requires the entire multidisciplinary team to be involved and understand its role. The process includes selecting the patient, obtaining and administering treatment, monitoring the patient, conducting follow-up calls, and coordinating with the hospital when escalation of care is necessary.

All of those responsibilities need to be clearly defined, including who is responsible for each step. At American Oncology Network, we have developed a standardized approach and created guidelines that delineate the responsibilities of each team member within the program.

Pharmacy Times: How do outpatient clinics prepare for, monitor, and manage CRS and ICANS, particularly during the step-up dosing period?

Maksour: CRS and ICANS were among the main barriers to moving step-up dosing into the outpatient setting. We use guidelines that outline how treatment and monitoring should be conducted.

The first step is patient selection. We must ensure that the patient is able to tolerate the treatment. However, even with appropriate patient selection, the incidence of CRS and ICANS can be high, although many cases of CRS are lower grade.

In some cases, we administer prophylactic tocilizumab, along with fluids and other premedications. Patients may return on the second and third days for additional fluids and dexamethasone, which can help mitigate the risk.

Patients are also instructed to monitor their temperature and vital signs at home. They need to call immediately and return for evaluation if they develop concerning symptoms, particularly fever.

Depending on the severity of the reaction, a patient may return to the clinic for treatment with tocilizumab. Patients with more severe symptoms may be sent to the hospital for additional treatment and possible inpatient admission.

Pharmacy Times: What payer or reimbursement challenges arise when clinics need to obtain and administer tocilizumab for patients receiving outpatient bispecific therapy, and how can these barriers affect treatment planning?

Maksour: Up to this point, we generally have not had significant problems obtaining payer approval for the bispecific therapies themselves. Payers are usually willing to authorize the bispecific for outpatient administration.

Tocilizumab is a different situation. When it is being used to treat active CRS, we typically do not encounter significant coverage issues. The problem arises when tocilizumab is used prophylactically.

We have experienced resistance from payers because they may not recognize the benefit of administering it before CRS develops. They may prefer to cover it only after the patient requires treatment.

Unfortunately, some physicians may not feel comfortable administering a bispecific therapy to a particular patient in the outpatient setting without upfront tocilizumab. In those cases, the patient may need to receive treatment in the hospital.

We try to work with payers, and sometimes an appeal can reverse the decision. In other situations, we may proceed without prophylactic tocilizumab when appropriate, or we may refer the patient to the hospital if the care team is not comfortable proceeding without it.

We hope payers will eventually recognize the potential benefit of approving tocilizumab upfront compared with the costs that may occur if the patient develops CRS and requires hospitalization.

Pharmacy Times: How should pharmacists and other clinicians educate patients and caregivers about outpatient bispecific therapy, including which symptoms to monitor, when to seek emergency care, and what to expect from the overall treatment experience?

Maksour: We want patients to feel comfortable with the therapy and be able to make an informed decision about whether they want to proceed. Bispecific therapy is a novel and effective treatment, and it can be administered safely in the outpatient setting for appropriate patients, but it is associated with adverse effects, including CRS and ICANS.

ICANS may present with symptoms such as confusion or headache. Patients need to understand that this is not a typical chemotherapy visit in which they receive treatment and immediately return home without additional monitoring.

During the first few step-up doses, patients may remain in the clinic for an extended period for observation. After they return home, they need to continue monitoring their temperature, blood pressure, and heart rate. They must also know when to contact the physician or seek emergency care.

Patients and caregivers need to be fully engaged in the process. Once the patient moves beyond the first couple of weeks, treatment generally becomes more routine and the risk of acute adverse effects decreases significantly.

It is not necessarily the easiest treatment to receive, but it is effective. As bispecific therapies move into the first- and second-line settings, we are going to see more patients receiving them, and care teams are becoming increasingly comfortable administering them.

Pharmacy Times: Is there anything else you would like to share with practices considering outpatient bispecific therapy?

Maksour: There are already several bispecific products on the market, and the development pipeline is extensive. We are going to see additional products and greater use in earlier lines of therapy.

Practices should not be afraid to begin offering these treatments, but they need to complete the necessary work upfront. They need bispecific-specific guidelines and standardized operating procedures.

Once a practice has treated its first few patients and established the process, the benefits become clearer, and patients can do very well on therapy.