How AON Built an Outpatient BiTE Therapy Program for Multiple Myeloma

Bispecific T-cell engager therapies have become an important option for patients with relapsed or refractory multiple myeloma, particularly those who have received several prior lines of therapy. Because these agents can be administered as an off-the-shelf treatment, they may offer a practical advantage in the community oncology setting compared with CAR T-cell therapy, which often requires referral to a specialized treatment center and additional lead time before treatment can begin.

In an interview with Pharmacy Times, Nicole McMullin, regional clinical pharmacist at American Oncology Network, discussed how AON developed an all-outpatient approach to step-up dosing for bispecific therapy in multiple myeloma. She highlighted the importance of patient selection, multidisciplinary coordination, pharmacist-led workflows, home monitoring, staff and patient education, and safety protocols for managing risks such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome.

Pharmacy Times: What makes bispecific T-cell engager therapy a meaningful advancement in the treatment of relapsed or refractory multiple myeloma, particularly in the community oncology setting?

Nicole McMullin: BiTE therapy has really revolutionized the way that we treat patients with multiple myeloma. In the research trials for BiTE therapy, these drugs produced an overall response rate of about 60% to 70% in a heavily pretreated population. These patients were refractory to several prior lines of therapy, so this response is really practice changing for patients who have limited remaining treatment options.

One of the other advantages of BiTE therapy is that it provides an off-the-shelf option for patients compared with CAR T-cell therapy. This makes BiTE therapy a great option, especially in the community setting, because patients do not have to be referred to a CAR T-cell treatment center.

Patients can also be treated more immediately with BiTE therapy compared with CAR T-cell therapy, which requires preparation of the CAR T cells and lymphodepleting chemotherapy. That process can require a lead time of up to 1 month before patients are able to receive treatment.

Pharmacy Times: AON has developed a comprehensive outpatient approach for step-up dosing with BiTE therapy. What were the key clinical, operational, and safety considerations that went into building that model?

McMullin: The first thing we did at AON was develop a standard operating procedure for the initiation of cellular therapy. We started specifically with BiTE therapies, such as the ones used in multiple myeloma, and more recently expanded that to CAR T-cell therapy.

The first clinical consideration was patient selection. We had to determine which patients were eligible and could be treated in an outpatient-only setting. We worked with providers to develop patient selection criteria for all-outpatient step-up dosing. Some of those criteria included that patients had to be located within 1 hour of the clinic, they had to have a reliable caregiver available 24/7 during the step-up period, and they could not have disease-specific characteristics that would place them at higher risk for cytokine release syndrome, or CRS, or immune effector cell-associated neurotoxicity syndrome, or ICANS. We also wanted patients to have access to a hospital within a reasonable distance.

In addition to patient selection criteria, one of our recommendations was to develop a multidisciplinary team at each clinic. These teams typically consist of a physician champion, an oncology pharmacist, clinic nurse managers, infusion nurses, and the financial team. Each member of that multidisciplinary team has a role in helping coordinate care for patients receiving bispecific therapies.

From a safety perspective, it was also important for patients to have immediate access to tocilizumab and other emergency medications if they experienced CRS or ICANS. We implemented home monitoring for CRS and ICANS during step-up dosing, and we required patients to be within 1 hour of a hospital in case they needed emergent treatment.

Education was another major initiative. The regional clinical pharmacists helped roll out education to the clinics. We developed education for each clinic, including recorded and live training, that walked through all the steps required to implement all-outpatient step-up dosing. This included education for staff on how to care for and triage these patients, as well as education for patients.

Another key recommendation was coordination with a local hospital. If patients develop symptoms of CRS or ICANS, it is important that they can be triaged to a local hospital. Building a strong partnership with that hospital, sharing standard operating procedures, and ensuring that the hospital has access to tocilizumab are all important parts of the model.

Pharmacy Times: What role does the oncology pharmacist play in preparing patients and care teams for outpatient BiTE therapy, particularly during step-up dosing and the early treatment period?

McMullin: Our regional clinical pharmacists receive a notification through our internal service ticket system when a patient is ordered one of the BiTE therapies for all-outpatient administration. When that comes across our screen, one of the first things we do is go into the patient’s chart and create a pop-up alert notifying anyone accessing the chart that the patient is receiving bispecific therapy.

We also place a memo in the chart so that anyone reviewing it knows the patient is receiving bispecific therapy. This is very important because if patients have delays in treatment, there are specific protocols that need to be followed to determine whether they need to be re-dosed with different step-up doses.

When step-up dosing is initiated, the regional clinical pharmacist also sends an email to the clinic that provides a breakdown of all the steps that must be in place before the patient can receive all-outpatient step-up dosing. This includes making sure the patient meets the selection criteria, asking the provider whether they want to use prophylactic tocilizumab, ensuring that the patient receives appropriate education, and including our standard operating procedures in one centralized communication.

The pharmacist also reviews the chemotherapy plan and makes sure all supportive care is in place for the patient.

Pharmacy Times: What safety protocols are most important when administering BiTE therapy in the outpatient setting, and how does your team monitor for potential complications during and after step-up dosing?

McMullin: The biggest concern with administering bispecific therapy in the outpatient setting is the increased risk for CRS and ICANS. We have focused on making sure patients are monitored effectively during the time period when CRS and ICANS are most likely to occur.

One of the first things we did was develop policies for monitoring CRS and ICANS, as well as a nurse triage document. If patients call in with symptoms of CRS or ICANS, nurses have a standard procedure for how to triage those patients appropriately.

For all patients receiving outpatient step-up dosing, we provide a patient monitoring kit. That kit contains a blood pressure cuff, thermometer, and pulse oximeter. For the first 3 days after step-up dosing, patients undergo monitoring at home every 6 hours. If they experience signs or symptoms of CRS or ICANS, they can call the clinic and be triaged by the nurse.

In addition to home monitoring, all patients are given a prescription for dexamethasone to have at home. We call this our “pill-in-pocket” dexamethasone. If patients experience symptoms of CRS, they can call the clinic nurse, who will triage the patient and contact the physician. If appropriate, the patient can immediately receive dexamethasone, which is one of the standard first treatment options for CRS.

Pharmacy Times: What patient and caregiver education is essential before initiating BiTE therapy, particularly regarding symptom recognition, when to contact the care team, and when to seek urgent evaluation?

McMullin: Having the patient and caregiver involved, screening them, and making sure they are able to appropriately follow the monitoring procedures is vital.

All patients undergoing outpatient step-up dosing receive a patient monitoring kit. The nurses or nurse educators at the clinic sit down with patients before treatment and provide comprehensive education on monitoring for CRS and ICANS. They review common adverse effects of BiTE therapy, signs and symptoms of CRS and ICANS, and how to use the blood pressure cuff, pulse oximeter, and thermometer.

Patients are also asked to demonstrate that they can use the equipment correctly. In addition, patients receive education materials on when to contact the care team. Fever is one of the biggest things we emphasize. We always educate patients that the first sign of CRS is often fever. If they develop a fever, they should call the clinic immediately so the nurse can follow triage procedures, contact the physician, and determine the next steps for management.

Pharmacy Times: As more community oncology practices consider outpatient BiTE administration, what lessons has AON learned that could help other teams build safe, scalable programs?

McMullin: One of the biggest recommendations I would have for other community oncology practices is to develop a multidisciplinary team at each clinic. This is vital to ensuring the success of these patients.

That multidisciplinary team should include a physician champion who wants to take on that role for the clinic. If colleagues have questions or need to collaborate on whether a patient is appropriate for outpatient step-up dosing, that physician champion can help guide those discussions.

It is also important to use advanced practice registered nurses. When patients are monitored after step-up dosing in the clinic, we require that they are seen in clinic for 2 days after receiving their step-up doses to monitor for CRS and ICANS. During those visits, patients can also meet with the APRN.

The pharmacy team is also important, including both the regional clinical pharmacist and the pharmacists or pharmacy technicians in the clinic. They help ensure that the correct medications are ordered, particularly during step-up dosing, because some BiTE therapies have different vial sizes that must be ordered correctly.

Financial counselors are another vital part of outpatient step-up dosing. They help ensure that authorization is in place for the BiTE therapy and, if clinics choose to use prophylactic tocilizumab, that authorizations are in place for both prophylactic and emergent use if patients develop CRS or ICANS.

Multidisciplinary coordination is really vital to a successful all-outpatient step-up dosing program. Practices should also consider prophylactic tocilizumab in patients. At AON, we have treated approximately 60 patients using this all-outpatient approach, and it has significantly reduced the rates of CRS that we have seen. Less than 20% of patients developed CRS during step-up dosing, and all of those cases were grade 1.

The final recommendation is to develop standard operating procedures so that everyone is on the same page and care is standardized. Assign roles within the multidisciplinary team, develop a triage document for managing CRS and ICANS, define how patients should be educated, and have a plan in place for educating all team members at the clinic who will be caring for patients receiving bispecific therapies.