Standardized Protocols Help Bring BiTE Therapy Into the Outpatient Setting

Bispecific T-cell engager therapies have become an important treatment option for patients with relapsed or refractory multiple myeloma (RRMM), particularly those who have received multiple prior lines of therapy.¹˒² These agents are designed to redirect T cells toward malignant plasma cells, and pivotal studies have shown meaningful activity in heavily pretreated populations.¹˒² In the pivotal MajesTEC-1 study (NCT04557098) supporting teclistamab (Tecvayli, Janssen Biotech, Inc.), the overall response rate was 61.8%, and in the phase 2 MagnetisMM-3 study (NCT04649359) of elranatamab (Elrexfio, Pfizer Inc), the overall response rate was 61.0%.¹˒²

In an interview with Pharmacy Times, Nicole McMullin, PharmD, BCOP, regional clinical pharmacist at American Oncology Network, discussed how bispecific T-cell engager, or BiTE, therapy is changing the treatment landscape for relapsed or refractory multiple myeloma and how AON developed an all-outpatient approach to step-up dosing. McMullin emphasized that safe outpatient administration requires patient selection, pharmacist-led workflows, home monitoring, caregiver education, access to emergency medications, and standardized protocols for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).³˒⁴

BiTE Therapy Offers an Off-the-Shelf Option in RRMM

“BiTE therapy has really revolutionized the way that we treat patients with multiple myeloma,” McMullin said. “In the research trials for BiTE therapy, these drugs produced an overall response rate of about 60% to 70% in a heavily pretreated population.”

For patients with RRMM, McMullin stated one of the major advantages of bispecific therapy is that it offers an “off-the-shelf” option compared with CAR T-cell therapy. CAR T-cell therapy can require referral to a specialized treatment center, manufacturing of patient-specific cells, lymphodepleting chemotherapy, and additional lead time before treatment begins.⁵ In contrast, bispecific therapy may allow some patients to begin treatment more quickly and closer to home, which can be especially important in the community oncology setting.⁴˒⁵

“This makes BiTE therapy a great option for patients, especially in the community setting, as they don’t have to be referred to a CAR T-cell treatment center, and patients can be treated immediately compared to CAR T-cell therapy,” McMullin said.

Building an Outpatient Step-Up Dosing Model

Outpatient administration requires careful planning because CRS and ICANS remain key safety concerns with immune effector cell therapies.³˒⁴ The American Society for Transplantation and Cellular Therapy consensus grading system defines and standardizes grading for CRS and neurologic toxicity, underscoring the need for consistent monitoring, escalation, and management across treatment settings.³

McMullin elaborates that one of AON’s first steps was developing a standard operating procedure for cellular therapy initiation, beginning with bispecific therapies used in MM and later expanding to CAR T-cell therapy. A central component of that work was determining which patients could safely receive step-up dosing in an outpatient-only model.

“The first clinical consideration that went into this process was to develop patient selection—which patients are actually eligible and can be treated in an outpatient-only setting,” McMullin said.

At AON, patient selection criteria include proximity to the clinic, caregiver support, disease-specific risk factors, and access to emergency care. McMullin said patients should be located within 1 hour of the clinic, have a reliable caregiver available 24/7 during the step-up dosing period, and have access to a hospital within a reasonable distance if urgent evaluation or treatment is needed. Patients also should not have disease-specific characteristics that place them at higher risk for CRS or ICANS.

AON also developed multidisciplinary clinic-based teams to support outpatient implementation. According to McMullin, these teams typically include a physician champion, oncology pharmacist, clinic nurse manager, infusion nurses, and financial team members. This type of coordinated infrastructure aligns with broader recommendations for outpatient bispecific antibody administration, which emphasize institutional readiness, team education, toxicity management pathways, and access to urgent care.⁴

“Each player in that multidisciplinary team has a role in helping with the coordination of care of these patients receiving bispecific therapies,” McMullin said.

Pharmacists Support Chart Alerts, Supportive Care, and Treatment Readiness

The oncology pharmacist plays a central role in preparing clinics and care teams for outpatient BiTE therapy. McMullin explained that regional clinical pharmacists receive an internal notification when a patient is ordered a bispecific therapy for all-outpatient administration. Pharmacists then review the patient’s chart and create pop-up alerts and chart memos to notify anyone accessing the record that the patient is receiving bispecific therapy.

This chart visibility is particularly important when treatment delays occur, McMullin said, because some bispecific therapies require specific redosing or repeat step-up dosing procedures after treatment interruptions.¹˒² Pharmacists also help ensure that supportive care medications and monitoring processes are in place before outpatient treatment begins.

“When step-up dosing is initiated, we send an email to the clinic, and it gives them a breakdown of all the steps that have to be in place before the patient can receive all-outpatient step-up dosing,” McMullin said.

That communication includes confirmation that the patient meets outpatient selection criteria, whether the provider wants to use prophylactic tocilizumab, whether patient education has been completed, and links to the standard operating procedures. Pharmacists also review the chemotherapy plan and confirm that supportive care measures are in place.

Home Monitoring and Triage Protocols Help Manage CRS and ICANS Risk

Safety planning is another core component of AON’s outpatient model. McMullin said the greatest concerns with outpatient bispecific therapy are CRS and ICANS, toxicities that require rapid recognition and standardized escalation.³˒⁴ AON developed policies for CRS and ICANS monitoring, as well as nurse triage documents to help standardize how symptoms are assessed when patients call the clinic.

“For all patients that do receive all-outpatient step-up dosing, we will give them a patient monitoring kit,” McMullin said. “That monitoring kit contains a blood pressure cuff, a thermometer, and also a pulse oximeter.”

For the first 3 days after step-up dosing, patients monitor at home every 6 hours. If they experience signs or symptoms of CRS or ICANS, they are instructed to call the clinic and speak with a triage nurse. McMullin said AON also provides patients with a prescription for dexamethasone to keep at home.

“We call it our pill-in-pocket dexamethasone,” McMullin said. “That’s readily available if patients do experience symptoms of CRS.”

If a patient develops symptoms, the nurse can triage the patient, contact the physician, and determine whether immediate dexamethasone administration is appropriate. McMullin also emphasized the importance of access to tocilizumab, which is commonly used in CRS management for immune effector cell therapies.³˒⁴ AON recommends coordination with local hospitals to ensure patients can be rapidly evaluated and treated if CRS or ICANS occurs.

Patient and caregiver education is also essential before outpatient step-up dosing begins. McMullin said nurses or nurse educators meet with patients before treatment to 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 included in the monitoring kit. Patients are also asked to demonstrate that they can use the equipment appropriately.

“Having the patient and the caregiver involved…and making sure they’re able to appropriately implement these monitoring procedures is vital,” McMullin said.

One of the most important symptoms patients are taught to report is fever. Fever is a defining symptom in CRS grading and can be an early sign that patients require further evaluation.³ McMullin said AON instructs patients to call the clinic immediately if a fever develops so the nurse can follow triage procedures, contact the physician, and determine next steps.

“We always educate our patients that really the first sign of CRS is going to be a fever,” McMullin said. “If they do develop a fever, they want to call immediately to the clinic.”

Lessons for Community Oncology Practices

For other community oncology practices considering outpatient bispecific therapy, McMullin said the most important lesson is to build a multidisciplinary team and standardize every step of care. She highlighted the importance of physician champions, advanced practice registered nurses, regional clinical pharmacists, in-clinic pharmacy staff, infusion nurses, and financial counselors.

Financial counselors play an important role in securing authorization for bispecific therapy and, when used, prophylactic or emergent tocilizumab. McMullin said this work is necessary to prevent access barriers from disrupting the outpatient treatment model.

McMullin also emphasized the need for standard operating procedures, clear role assignment, CRS and ICANS triage documents, patient education materials, and training plans for all clinic staff involved in the care of patients receiving bispecific therapies. These steps are particularly important as more practices explore outpatient bispecific administration and work to balance access, safety, and operational feasibility.⁴

At AON, McMullin said approximately 60 patients have been treated using the all-outpatient approach. According to McMullin, less than 20% developed CRS during step-up dosing, and all CRS cases were grade 1.

“What we found with our patients…is that it has significantly reduced our rates of CRS that we’ve seen,” McMullin said.

As bispecific therapy continues to move into community oncology, McMullin’s experience highlights the expanding role of pharmacists in supporting complex immune-based therapies outside the hospital. For outpatient step-up dosing to be safe and scalable, practices need more than clinical protocols; they need coordinated teams, educated patients and caregivers, real-time monitoring pathways, medication access planning, and standardized workflows that allow every team member to respond quickly when symptoms emerge.

REFERENCES

1. Baines AC, Kanapuru B, Zhao J, et al. FDA Approval Summary: Teclistamab-A Bispecific CD3 T-Cell Engager for Patients with Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2024;30(24):5515-5520. doi:10.1158/1078-0432.CCR-24-1872

2. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9

3. Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758

4. Garfall AL, Banerjee R, Frenzel L, et al. A roadmap to implementing outpatient administration of bispecific antibodies in multiple myeloma. Front Oncol. 2025;15:1630146. Published 2025 Jul 30. doi:10.3389/fonc.2025.1630146

5. FDA. FDA grants accelerated approval to elranatamab-bcmm for multiple myeloma. Published August 14, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-elranatamab-bcmm-multiple-myeloma