Blinatumomab Administration in Pediatric B-Lineage ALL: Expert Recommendations From the Children’s Oncology Group

Abstract

BACKGROUND

The addition of blinatumomab to chemotherapy is the new standard of care for most pediatric patients with B-lineage acute lymphoblastic leukemia (B-ALL), and its use has increased rapidly. Administering blinatumomab to pediatric patients is associated with a spectrum of unique challenges, resulting in variable practices across institutions.

OBJECTIVES

This article presents expert recommendations for blinatumomab administration in patients with pediatric B-ALL.

METHODS

Pediatric oncology nurses, physicians, and pharmacists collated current evidence and Children’s Oncology Group institutional experiences to identify considerations for planning for blinatumomab administration, initiating and managing infusions, and monitoring for adverse events.

FINDINGS

Engaging patients, families, and clinicians promotes care transitions between inpatient and outpatient settings and minimizes complications. Ongoing institutional commitment to monitor and capture emerging trends in blinatumomab administration can inform future optimal care practices.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) is the most common malignancy in children, with 5.4 new cases per 100,000 children per year in the United States (National Cancer Institute [NCI] Surveillance, Epidemiology, and End Results Program, 2025). Survival rates for childhood B-lineage ALL (B-ALL) have improved dramatically over the past 50 years (Hunger & Mullighan, 2015). However, attempts to improve cure rates with intensification of traditional chemotherapy have failed (Angiolillo et al., 2017; Attarbaschi et al., 2020; Conter et al., 2024; Kirkwood et al., 2022; Maloney et al., 2020; Mattano et al., 2014). Blinatumomab, an anti–cluster of differentiation(CD)19 and anti-CD3 T-cell engager, has been shown to improve outcomes among adults with ALL (Litzow et al., 2024). In pediatrics, blinatumomab has been studied in the Children’s Oncology Group (COG) trial for relapsed ALL (AALL1331; NCT01471782), informing a new standard of care in the relapsed setting (Brown et al., 2021). Given efficacy in relapsed/refractory disease, blinatumomab was then studied in a COG trial (AALL1731; NCT03914625) for children with NCI standard-risk (SR) B-ALL. Results of this trial demonstrated exceptional outcomes for children with SR-average or SR-high B-ALL treated with two nonsequential postconsolidation cycles of blinatumomab in addition to standard chemotherapy, with a combined three-year disease-free survival of 96%, compared to 87.9% with standard chemotherapy alone (Gupta et al., 2024). The excellent outcomes for SR-high patients who received blinatumomab (94.1%) in comparison to those who received chemotherapy alone (84.8%) have been extrapolated to patients with NCI high-risk B-ALL, where the addition of blinatumomab is recommended as the new standard of care (Gupta et al., 2024). Patients classified as favorable risk did not receive blinatumomab on AALL1731 and are not projected to receive blinatumomab due to their excellent outcomes with chemotherapy alone. However, other pediatric B-ALL populations have also demonstrated survival advantages with the addition of blinatumomab, including infants with KMT2A-rearranged ALL. In a pilot study conducted by the Interfant network (EudraCT 2016-004674-17), the addition of one cycle of blinatumomab to chemotherapy increased two-year disease-free survival to 81.6% from 49.4% reported on the prior Interfant-06 trial (van der Sluis et al., 2023). Given the projected dramatic increase in the use of blinatumomab in pediatric B-ALL, it is important to review and share blinatumomab best practices and challenges. Updates to guidelines and published resources have not kept pace with clinical experience. Published best practices can inform institutional practices and processes that optimize delivery and the patient and family experience.

Blinatumomab cycles, or “blocks,” are administered via continuous IV infusion over 28 days; they are typically initiated in the inpatient setting and often transitioned to the home setting if the child tolerates the infusion well (Montgomery et al., 2024). Therefore, blinatumomab administration often presents significant challenges. Pediatric and adult oncology clinicians report difficulties with managing issues with central venous access devices (CVADs), such as line selection, infusion interruptions, blood back flow, flushing, occlusions, and management of transitions between the inpatient and outpatient settings (Montgomery et al., 2024; Szoch et al., 2018; Withycombe et al., 2024). Solutions to these challenges differ between adult and pediatric practice and are often attributed to institutional policies, provider preferences, or clinician comfort or abilities, or by requirements unique to age and/or developmental stage. For example, it is more common for adult patients to receive blinatumomab through a peripherally inserted central catheter (Szoch et al., 2018), whereas pediatric patients typically receive blinatumomab via an implanted port (Withycombe et al., 2024). Furthermore, adult clinicians describe collaborating with home infusion companies to manage outpatient blinatumomab infusions (Szoch et al., 2018), whereas only 43 of the responding 150 COG-affiliated institutions report partnering with a home infusion company (Withycombe et al., 2024).

Pediatric and adult oncology clinicians rely on interprofessional collaboration to safely administer blinatumomab to patients (Bernhardt et al., 2021; DePadova et al., 2016; Montgomery et al., 2024). Despite consistency in the types of institutional processes developed for safe delivery of blinatumomab, there remains a lack of a published, systematic, standardized approach to addressing these common challenges of blinatumomab delivery. This gap is problematic as institutions request additional support to facilitate blinatumomab administration (Montgomery et al., 2024). The need for additional support and guidance will be exacerbated by the immediate need to deliver blinatumomab to most pediatric patients newly diagnosed with B-ALL. The increase in patient volume will be acutely felt by 75% of COG institutions that previously reported treating fewer than 10 patients per year with blinatumomab (Withycombe et al., 2024).

Purpose

The COG Nursing Discipline has previously characterized blinatumomab administration practices (Withycombe et al., 2024) and explored challenges and facilitators to administration (Montgomery et al., 2024). Pediatric researchers and clinicians from individual institutions have also described administration issues and published guidance for blinatumomab administration (Bernhardt et al., 2021; Moody et al., 2024; Oranges et al., 2020). Many of the previously reported complexities of care, including line selection and care, management of inpatient and outpatient care, and administration issues, have evolved since COG trial AALL1731 opened to accrual in June 2019 because of experience gained treating a younger population with SR B-ALL receiving blinatumomab within COG. The COG Nursing Discipline presents considerations and expert recommendations for blinatumomab administration in pediatrics organized by key processes: (a) planning for blinatumomab administration, (b) initiating and managing blinatumomab infusions, and (c) monitoring for adverse events.

Recommendations for Blinatumomab Administration in Pediatrics

Planning for Blinatumomab Administration

There are several key steps associated with planning for blinatumomab infusion (see Table 1). It is imperative to assess both patient/family and institutional characteristics that may affect the blinatumomab administration plan, including intrathecal chemotherapy prophylaxis, which is recommended to prevent central nervous system ALL relapse. Other considerations when determining setting(s) in which the patient will receive blinatumomab include the patient’s age, developmental level, and activity level; distance from residence to treating institution; caregiver’s perceived coping and support; frequency of bag changes; type of CVAD and line securement; and the patient’s and caregiver’s educational needs. It is also important to determine the ambulatory infusion pump type, supplier-associated agreements, and financial support for blinatumomab-specific patient/family resources (e.g., medication carrying bag).

TABLE 1.

KEY ELEMENTS AND NURSING CONSIDERATIONS WHEN PLANNING BLINATUMOMAB ADMINISTRATION

KEY ELEMENTS	NURSING CONSIDERATIONS	EXAMPLE OF INSTITUTIONAL CARE STANDARD
Patient and family characteristics	■ Assess patient and family needs. □ Consider the developmental level of patient; younger and/or very active children and those with disabilities may require additional care planning. □ Conduct a psychosocial assessment to assess patient’s and family’s coping with a 28-day infusion delivered mostly outpatient, ability to care for the CVAD and pump tubing, and ability to travel to and from the treating institution.	■ Involve child life specialists to assist with coping, normalizing the continuous infusion. ■ Engage social work team to assist with financial and other resources when appropriate.
Institutional characteristics	■ Determine availability of a home health agency to support outpatient blinatumomab infusion, including supplying ambulatory infusion pumps. ■ Determine the ambulatory infusion pump type, supplier, and payment considerations. ■ Note that hospitals in the United States will need to consider insurance coverage for commercial supply.	■ When needed, initiate the process to obtain a third-party payer prior authorization for inpatient and outpatient infusion weeks prior to planned start. □ Submit a request for both inpatient and outpatient infusions. □ The third-party payer then reviews the request and decides whether to approve or deny coverage □ Denials may require further action (submission of data, peer-to-peer review).
Drug initiation and admission duration	■ Determine start date and tentative length of inpatient stay. □ Establish institutional guidance for the preferred inpatient dosing and associated medication bag duration (e.g., 24-hour bag). □ Establish institutional criteria for standard recommended length of hospitalization with initiation of cycles and criteria for hospital discharge. □ Review U.S. Food and Drug Administration prescribing information on bag size selection, including insurance coverage.	■ First blinatumomab block: minimum 72-hour LOS for patients in remission with negative MRD (MRD-negative) ■ Second blinatumomab block: minimum 48-hour LOS for patients in MRD-negative remission
Timing of bag changes with outpatient delivery	■ Determine tentative schedule for bag changes and follow-up visits. □ Involve family in the planning process. □ Determine location where bag changes will occur (hospital/clinic versus home via home health agency).	■ Create a modifiable patient/family calendar that includes planned admission date(s), bag change dates, and clinic visits. ■ Instruct families to arrive 1 hour before bag change is due to account for unexpected delays. ■ When possible, coordinate bag changes between noon and 3 pm.
Patient/family education	■ Ensure families receive verbal instruction and have written education materials regarding possible side effects of blinatumomab, equipment and troubleshooting, CVAD/dressing care, hygiene and bathing, strategies to secure the tubing at home, and contact telephone numbers of care team/home health agency. ■ Adapt patient/family education tip sheet template with institution-specific details. ■ Assess language preferences and need for interpreters.	■ Pediatric oncology nurses provide 1:1 patient/family education using standardized content prior to or during admission (e.g., CVAD care at home, side effects, bathing). ■ Patients/families receive written visual materials, including diagrams of ambulatory pump with explanations of settings and anticipated home infusion–related issues and pump alarms (e.g., air-in-line alarm, reservoir volume low, occlusion). ■ Contact telephone numbers for varied hours of the day and weekend provided
Clinician education	■ Pediatric oncology nurses should receive specific education regarding safe delivery of blinatumomab. ■ Institutional line-flushing practices ■ Coordination of care to avoid interruptions of more than 1 hour	■ Institutional nursing care sheet specific to blinatumomab with information on flushing policies, infusion interruptions, and use of the line infusing blinatumomab for clinical care

CVAD—central venous access device; LOS—length of stay; MRD—minimal residual disease

Note. Based on information from Amgen, 2024; Withycombe et al., 2024.

Early planning regarding details of the initial blinatumomab infusion, including admission duration, bag size, and ambulatory pump type, is recommended. The hospital observation period for a patient’s first exposure to blinatumomab varies and is reported as between one and nine days (Moody et al., 2024; Oranges et al., 2020). Just over one-third of COG institutions previously reported the length of hospital stay for the first exposure to blinatumomab as 72 hours or less (Moody et al., 2024; Oranges et al., 2020; Withycombe et al., 2024). However, the current U.S. Food and Drug Administration (FDA) prescribing information recommends that clinicians monitor patients for a minimum of 72 hours with first blinatumomab exposure in the consolidation phase (Amgen, 2024). In the context of administering blinatumomab in pediatric patients who achieve minimal residual disease (MRD)–negative remission, institutions have endorsed shorter observational periods. Institutional-level decisions for inpatient observation periods should consider FDA recommendations, institutional experience, and published toxicity rates.

Blinatumomab is mixed in different bag sizes to accommodate infusion over time, including 24-, 48-, 72-, 96-, and 168-hour (i.e., seven-day) bags (Amgen, 2024). For patients who received investigational blinatumomab on prior COG ALL trials, 72-hour and 96-hour infusion bags were the most commonly used in the outpatient setting and are familiar to COG institutions (Withycombe et al., 2024). While accounting for specific patient characteristics (e.g., active toddlers), benzyl alcohol content, and potential for drug waste should disconnection/contamination occur, blinatumomab bags allowing the longest interval between changes should be planned and ordered. These decisions regarding bag sizes and durations affect the institutional and home health pharmacies that prepare the blinatumomab bags and the patient’s and family’s quality of life.

Preferably, pediatric patients should receive blinatumomab via an ambulatory infusion pump for both inpatient and outpatient administration. There is substantial variability across COG institutions regarding the carrying bags and source of the pump. Bags may be purchased by the families or provided by the institution, and pumps may be owned by the institution and loaned to the patient, rented from another company, or provided by a home health agency. Variability also exists in the infusion time/bag size, location of bag changes (such as home versus clinic), and central line type (Montgomery et al., 2024; Withycombe et al., 2024). These practice variations affect how institutions prepare patients and families, along with clinicians, for the initial blinatumomab infusion. Templates for education for clinicians, and for patients and families, should be used to improve efficiency and consistency across sites whenever possible. Sharing and testing of standardized resources for the provision of patient and family education is an important next step.

Initiating and Managing Blinatumomab Infusions

Initiating blinatumomab in the hospital and transitioning to the outpatient setting involves an interprofessional approach (see Table 2). Regardless of the anticipated length of hospital stay, blinatumomab is best administered via an ambulatory infusion pump, allowing for the same low CVAD infusion rate that will be continued at home. The continuous ambulatory drug delivery and CURLIN infusion pumps are the most used ambulatory infusion pumps reported by COG institutions (Withycombe et al., 2024). Use of such pumps during inpatient blinatumomab administration avoids the need for companion IV solutions and promotes patient and family education and comfort with the pump that will be used for outpatient administration. Infusion rates for pediatric patients are variable (0.6 ml per hour to 10 ml per hour) and are determined by the medication bag size and volume.

TABLE 2.

KEY ELEMENTS AND NURSING CONSIDERATIONS FOR ADMINISTRATION OF BLINATUMOMAB

KEY ELEMENTS	NURSING CONSIDERATIONS	EXAMPLE OF INSTITUTIONAL CARE STANDARD
Equipment (infusion pump, power source, CVAD emergency kit, medical backpack)	■ Use ambulatory infusion pumps (e.g., CADD) if possible during hospital admission to facilitate outpatient transition. □ If an inpatient infusion pump must be used, a companion solution of normal saline can be used at the lowest rate possible to maintain the infusion through the central line (e.g., 10 ml per hour). □ During initial days of inpatient stay, consider use of smaller bag sizes and observe for patient tolerance. □ Consider using the medication bag size that allows the longest infusion duration possible after the patient tolerates the medication to reduce the frequency of bag changes. □ Provide medical-grade, pediatric-friendly backpacks to hold pump and medication safely.	■ Use 24-hour bags during the hospitalization when blinatumomab is initiated. ■ If 24-hour bags are tolerated, use bag size that allows for the longest infusion between changes. ■ Consider implementing an ambulatory infusion pump agreement form with families for institution-owned pumps. ■ Provide families with “blinatumomab go-bags” with necessary additional supplies for home (e.g., pump batteries, dressings, line guards).
Initiating infusion	■ Coordinate with the medical and pharmacy teams to determine the optimal start time. □ Consider drug preparation time. □ Consider risk for initial infusion-related reactions. ■ Ensure required observations and clinical assessments have been completed prior to infusion start. ■ Verify premedications have been ordered and given prior to infusion start.	■ Administer subsequent bags close to the same time as the previous bag. ■ Altering the bag change time can be considered and discussed with the medical team if blinatumomab was initiated in the evening and evening bag changes are not feasible in the outpatient setting.
Patient assessment	■ Nurse-to-patient ratio should consider patient’s risk for toxicity (linked to disease status; patients in MRD-negative remission low risk for grade 3 or higher toxicity). ■ Patients with Down syndrome are at increased risk for neurotoxicity/seizures during blinatumomab infusion. ■ Determine preferred CVAD for infusion (e.g., implanted port). ■ A second CVAD or placement of a peripherally inserted venous device is not recommended for patients who have achieved MRD-negative remission prior to receiving blinatumomab.	■ Vital signs including temperature: every 4 hours if patient is stable or per institutional policy ■ Neurologic assessments: Institutions employ a range of intervals (every 4–24 hours). □ Observe child’s behavior and ask caregivers whether child’s behavior is typical. □ Use age-based tasks such as sticker charts or writing samples (e.g., patient’s name). □ Cornell Assessment of Pediatric Delirium or Immune Effector Cell–Associated Encephalopathy assessments
Infusion pump programming	■ Ensure all nurses are educated and competent in managing ambulatory infusion pumps. ■ Determine whether blinatumomab can be added to the ambulatory infusion pump drug library. ■ Determine the available drug formulations, including bag sizes and associated infusion rates. □ All medication bags will contain overfill; there should be leftover drug with every bag change. ■ Most ambulatory infusion pumps have a 10% or less margin of error, and infusions may end earlier or later than expected. □ If an infusion time exceeds the 10% variance, it is recommended to send the pump to medical engineering for assessment and to switch to an alternate pump.	■ Blinatumomab infusion bags range from 24-hour to 168-hour (7-day) in varied concentrations. Infusion rates typically range from 0.6 ml per hour to 10 ml per hour, depending on prescribed concentration and dosage.
Infusion pump tubing	■ Determine the specific tubing supply and preferred setup, and ensure compatibility with blinatumomab and selected pump. ■ Refer to the latest version of the National Institute for Occupational Safety and Health guidelines or institutional policy regarding the use of CSTDs. □ A CSTD will add extra weight to the line and can affect the accuracy of the pump.	■ Requires a dedicated lumen of a CVAD ■ Drug preparation: Removal of air from the bag is crucial when infusing via CADD pumps, especially when preparing 72-hour, 96-hour, and 168-hour (7-day) bags. ■ Tubing: DEHP-free tubing □ Tubing should be changed and primed with drug with each new bag. ■ Filter: 0.2-micron in-line filter is required for 24-hour and 48-hour bags. □ Do not use an in-line filter for 72-hour, 96-hour, and 168-hour (7-day) bags. □ No added CSTD after institutional review and agreement to have an exception to policy
Flushing and blood work	■ Follow institution-specific guidelines for drawing blood work and flushing the line. □ Blood may be drawn from the same CVAD lumen as the infusion for laboratory work when clinically indicated. □ Flush the line to ensure patency with each bag change.	■ Minimize CVAD flushing volume for CVAD care, drawing blood for laboratory work, administering medications for procedural sedation, and completion of infusion.
CVAD care	■ Follow institution-specific guidelines for process and frequency of CVAD care (e.g., dressing, cap, and implanted port needle changes). ■ CVAD care should be coordinated with bag changes. ■ The use of topical anesthetic is encouraged to minimize pain with implanted port access. ■ Consider quicker-acting topical anesthetic to reduce time of infusion interruption.	■ 96-hour bags: Establish a policy exception to allow CVAD dressing and implanted port needle changes to occur every 8 days and cap changes every 4 days. ■ 168-hour (7-day) bags: Establish a policy exception to allow CVAD cap changes to occur every 7 days.
Infusion interruptions	■ Interruptions will be necessary for CVAD care (cap and implanted port needle changes) and bag changes. □ If the medication bag or tubing sterility is compromised, a new bag should be obtained. ■ If a line becomes occluded, the infusion will be interrupted to administer thrombolytic medications per institutional policy. ■ Document and notify the medical team for any interruptions of 1 or more hours. ■ If the infusion is interrupted for 4 or more hours, reinitiation of the infusion in a medical facility with monitoring and/or hospitalization is recommended. ■ Infusions can be interrupted to administer supportive medications, including procedural sedation.	■ For infusion interruptions totaling more than 24 hours, the medical team may choose to administer the cumulative missed dose beyond the planned infusion duration. ■ If the time of infusion interruption is expected to be extended (more than 4 hours), administering blinatumomab using a peripheral IV can be considered in the hospital setting. ■ Consider an order for a contingency bag or an emergency bag that is checked and verified by an oncology pharmacist and can be activated should a new bag be needed during nights, weekends, and/or holidays.
Patient/family readiness for discharge	■ Reassess patient and family needs, and tailor the plan for outpatient infusion. ■ The following is based on who will manage the outpatient infusion: □ Option 1: treating institution manages blinatumomab infusion □ Option 2: home health agency and treating institution co-manage blinatumomab infusion	■ Option 1: Blinatumomab supply, bag changes, CVAD management, and CVAD dressing changes are handled by the primary institution, and no home health agencies are involved in the care of the patient. ■ Option 2: The home health agency may provide medication, infusion pump, and home nursing support. The home health RN may meet the patient at the hospital prior to discharge to initiate the home infusion of blinatumomab. The patient should return to the institution at intervals for needle change/laboratory tests and provider visits; this is typically coordinated with the day of bag change. The patient should contact home care for any infusion complications with the pump/tubing/needle/access and primary oncology team for any clinical symptoms or concerns.
Outpatient bag changes	■ Coordinate with the medical and pharmacy teams to determine the optimal time for bag changes. □ Consider drug preparation time. □ Coordinate appointment time with pharmacy/home health. ■ Ensure required observations are completed at the outpatient visit.	■ Administer subsequent bags close to the same time as the previous bag. ■ Home health agency to coordinate visit times around school and individual family needs

CADD—continuous ambulatory drug delivery; CSTD—closed-system transfer device; CVAD—central venous access device; DEHP— di(2-ethylhexyl)phthalate; MRD—minimal residual disease

Note. Based on information from Amgen, 2024; Herr et al., 2020; Traube et al., 2014; Withycombe et al., 2024.

The relatively low blinatumomab infusion rates have created challenges and uncertainties related to infusion interruptions for necessary clinical care, such as CVAD flushing, laboratory draws, bag changes, cap changes, and implanted port needle changes. Institutions have also described infusion interruptions to administer sedation for required procedures, such as delivery of intrathecal chemotherapy (Withycombe et al., 2024). In these cases, it is not recommended to place additional lines for routine cancer care. Minimizing interruptions to less than one hour through careful care coordination is recommended in COG clinical trials. Consideration should be given to aligning flushing and central line care practices with current institutional practice; however, deviations from current practices and policies may need to be considered after review of potential risks and benefits. One example is extending the length of time between implanted port needle changes to align with planned bag changes, therefore minimizing infusion interruptions.

SEVEN-DAY (168-HOUR) BAGS

The goal of using seven-day blinatumomab bags is to minimize infusion disruptions and allow for greater intervals between appointments or home health visits for bag changes. Due to low infusion rates (0.6 ml per hour), concerns for line patency and blood backup, as well as flushing volumes and potential drug waste, have been raised with the seven-day blinatumomab infusion bags. Drug waste is a consideration, as a disconnection or dislodged CVAD needle early in the course would result in waste of a large volume of drug. To reduce the risk of blood backing up in the line, an ambulatory infusion pump must be used, and in-line filters should not be used. Careful consideration of appropriate patients for seven-day bags is warranted. Although there is positive anecdotal experience of delivering blinatumomab with seven-day bags to children, formal collection of data to document feasibility of this approach could facilitate adoption across institutions of varied size and experience with blinatumomab administration in pediatrics.

INFANTS

Administering blinatumomab to infants presents unique challenges, including line selection, risk of fluid overload with blinatumomab formulations requiring infusion rates of 10 ml per hour, and, importantly, the potential risk of toxicity with the use of 72-hour, 96-hour, and 168-hour (seven-day) bags that contain benzyl alcohol preservative. In December 2024, the FDA approved changes to the blinatumomab U.S. prescribing information that included the addition of 72-hour and 96-hour bags prepared with bacteriostatic 0.9% sodium chloride injection (containing 0.9% benzyl alcohol) (Amgen, 2024). The U.S. prescribing information states that the use of 72-hour, 96-hour, or 168-hour (seven-day) blinatumomab bags containing 0.9% benzyl alcohol is not recommended for patients weighing less than 5.4 kg. As a result of this change, infants who weigh less than 5.4 kg who are treated at U.S. cancer centers should receive 24-hour or 48-hour bags of blinatumomab prepared with preservative-free 0.9% sodium chloride. Blinatumomab prescribing information in other countries (e.g., Canada, Switzerland, Ireland, the Netherlands) has not been amended as of May 2025 and allows for use of preservative-free 0.9% sodium chloride to prepare 72-hour and 96-hour bags at volumes and infusion rates significantly different than those approved by the FDA in the United States (European Medicines Agency, 2024). Institutions should refer to their country-specific prescribing information or the study protocol (for patients registered on clinical trials) when deciding on blinatumomab bag selection and preparation.

Monitoring for Adverse Events

The most reported toxicities of blinatumomab are cytokine release syndrome (CRS) and neurotoxicity (see Table 3). Although blinatumomab has a favorable toxicity profile, it is common for patients to experience fever as a sign of low-grade CRS with initiation of blocks (Amgen, 2024). The risk of CRS can be mitigated with the use of dexamethasone prophylaxis prior to the first dose of blinatumomab during the first block, with a planned dose escalation, and when restarting an infusion after an interruption of four or more hours. In some cases, the use of corticosteroid premedication may also be warranted prior to initiation of blinatumomab during the second block, depending on provider preference.

TABLE 3.

KEY ELEMENTS AND NURSING CONSIDERATIONS WHEN MONITORING FOR ADVERSE EVENTS WITH BLINATUMOMAB

KEY ELEMENTS	NURSING CONSIDERATIONS	EXAMPLE OF INSTITUTIONAL CARE STANDARD
Fever	■ Common adverse event, especially during initial days of infusion ■ May extend the hospital length of stay if fevers persist ■ Follow institutional guidelines for fever management.	■ It is acceptable to interrupt the infusion to obtain blood cultures and other laboratory values and to use the lumen infusing blinatumomab to administer antibiotics if indicated.
CRS	■ Mild CRS is expected and should be anticipated with blinatumomab. ■ Moderate to severe CRS is uncommon and could involve stopping the infusion and consideration of other medications for management. ■ Institutions should consider CRS grading and management standards and associated tools.	■ Vital signs monitoring per institutional guidelines, typically every 4 hours during hospitalization ■ Anticipatory guidance to patients and families that mild CRS is common, with associated fever
Neurotoxicity and ICANS	■ Central neurotoxicity is more common than peripheral; therefore, monitoring of neurologic status is required. ■ Neurotoxicity and ICANS typically occur in the initial days of infusion, but can occur in any cycle and at any point in a cycle. ■ Patients with Down syndrome are at higher risk of neurotoxicity, including seizures.	■ Institutions employ a range of neuroassessment intervals (every 4–24 hours) during inpatient stays following initiation of blinatumomab. ■ All patients with Down syndrome should start antiepileptic prophylaxis at least 12 hours prior to blinatumomab infusion and continue for the duration of the infusion.
Immune function	■ Hypogammaglobulinemia is a common adverse event. ■ Monitor IgG levels during therapy.	■ Replete with IV immunoglobulin to maintain IgG level per institutional standard.

CRS—cytokine release syndrome; ICANS—immune effector cell–associated neurotoxicity syndrome; IgG—immunoglobulin G

Note. Based on information from Li et al., 2021; National Cancer Institute Cancer Therapy Evaluation Program, 2017; Wo et al., 2022.

Fever management, both at blinatumomab initiation and during the 28-day block, would benefit from standardization. Pediatric patients will have a CVAD for administration and are considered immunocompromised but are unlikely to be neutropenic during blinatumomab administration. Guidelines for fever management in pediatric oncology, such as the COG-endorsed supportive care guidelines (COG, 2023), typically recommend obtaining a complete blood count and blood cultures and considering empiric antibiotic treatment.

The neurotoxicity reported with blinatumomab, immune effector cell–associated neurotoxicity syndrome, is a distinct and noteworthy complication of immunotherapy. Symptoms commonly manifest in the first two weeks of blinatumomab cycles and can include headache, tremors, ataxia, confusion/disorientation, encephalopathy, malaise, seizure, somnolence, speech disorders, and coordination or balance disorders (Amgen, 2024). Children with Down syndrome are at increased risk for seizures, and antiepileptic prophylaxis is recommended (e.g., levetiracetam or alternative agent) starting at least 12 hours before the blinatumomab blocks and continuing through completion of each block (Li et al., 2021). The underlying pathophysiological mechanism resulting in blinatumomab-related neurotoxicity remains unknown. There is currently no standardized formal assessment strategy or recommended frequency for neurologic evaluation, with some institutions considering routine clinical observation and engagement with the patient to assess appropriate behaviors as an adequate strategy. Pediatric patients appear to be less susceptible to blinatumomab-associated neurotoxic side effects, with much lower rates of reported neurotoxicity compared with adults (Bhojwani et al., 2021; von Stackelberg et al., 2016), and there are currently no standardized recommendations for pediatric patient activities; however, given the lower risk of reported neurotoxicity, adoption of adult guidelines is not appropriate.

In addition to these risks, patients receiving blinatumomab have a high likelihood of developing hypogammaglobulinemia and an increased risk for infections. Monitoring serum immunoglobulin G (IgG) levels and replacement with IV immunoglobulin (IVIG) is often recommended in clinical trial protocols, although optimal time points for the checking of IgG levels and the benefit of administering IVIG have not been established (Wo et al., 2022). The anticipated duration and resolution of hypogammaglobulinemia post–delivery of blinatumomab is also unknown. Development of guidelines for replacement of IVIG in this population is underway.

Discussion

Institutions caring for children with B-ALL must be prepared to administer blinatumomab to an increasing number of patients. When administered in the postconsolidation phase of therapy to patients who have achieved MRD-negative remission, the toxicity profile of blinatumomab is favorable (Gupta et al., 2024; Marrapodi et al., 2022). It is important to address issues such as facilitating optimal outpatient care for patients and families, answering persistent clinical care questions, standardizing patient and family education, and gathering evidence to support blinatumomab administration.

Given that the standard-of-care therapy for most patients with pediatric B-ALL will now include blinatumomab, the diversity and unique needs of each family must be considered. Care planning for blinatumomab should include patient and family assessments specific to the burden of care with home administration. Previously, it was recommended that families stay a reasonable distance from the treating institution when a home health agency was not available to ensure timely access to expert care for medical concerns, bag changes, and infusion-related complications. This may not be sustainable moving forward, as institutions may be unable to support housing near the treating institution for a growing patient population. In addition, requiring families to be away from home for prolonged periods could be considered an added burden. The use of 168-hour, or seven-day, bags may help to reduce necessary visits and align with once-weekly provider visits.

Early patient and family assessments should include perceived coping difficulties with outpatient or home infusion of blinatumomab. Assessment can lead to the involvement of child life, psychology, and/or developmental pediatric specialists to support individualized care planning. Patient and family education should be presented in phases and ideally initiated weeks in advance of starting blinatumomab, with more detailed education reinforced during the initial hospital stay.

Institutions will need to consider how to support families traveling to and from home for management of medical concerns and infusion complications. In a retrospective review of blinatumomab administration at a single specialized pediatric cancer institution, almost half of the cycles administered required clinical staff intervention, but less than 10% required hospital readmission (Moody et al., 2024). Developing processes that incorporate specialized oncology care can minimize both infusion interruptions and unplanned hospital visits. Some institutions have developed processes such that families can call oncology nurses, at all hours, to assess and troubleshoot infusion-related concerns, increasing the likelihood of solving the infusion-related problems. If a hospital visit is needed for an infusion-related concern, arranging for care by oncology nurses familiar with implanted ports, ambulatory infusion pumps, and blinatumomab can lead to rapid resolution and minimize infusion interruptions. In addition, hospital visits for medical concerns warrant consideration for expedited care by oncology experts. One example includes diverting febrile patients receiving blinatumomab to pediatric oncology units instead of emergency departments. Future goals should also include developing flexible options for outpatient care and exploring innovative care delivery such as telehealth and an expert on-call blinatumomab service for community-based clinicians.

Implications for Nursing Practice

In late 2024, the COG Nursing Discipline summarized recommendations from pediatric oncology clinicians related to blinatumomab administration, encompassing a range of topics including increasing active learning opportunities, sharing institutional experiences, enhancing infusion-related guidance, and creating family education materials (Withycombe et al., 2024). Despite increasing experience with administering blinatumomab to pediatric patients with B-ALL, nurses continue to share concerns related to blinatumomab. Continuing concerns include flushing practices, central line care, access to the drug, support for outpatient delivery, and best practices for preparing patients and families. This article takes the initial steps to provide more detailed guidance in response to the need for institutions to share experiences and more specific details regarding how to administer blinatumomab across care settings. With the goal of a “quality approach to blinatumomab delivery” (Withycombe et al., 2024), institutions should implement systems that support developing, evaluating, and revising blinatumomab-specific processes. Institutions should monitor and characterize facilitators, barriers, and unexpected complications.

Conclusion

Blinatumomab, administered in combination with chemotherapy, has led to superior disease-free survival compared with chemotherapy alone for children with SR B-ALL. Blinatumomab administration is associated with unique benefits and challenges for pediatric patients of all ages, requiring multi-institutional and interprofessional collaborations to promote safe and effective care. Sharing expert recommendations through publication is one way to reduce inefficiencies and promote consistent care across institutions. New challenges are likely to emerge as institutions administer more blinatumomab to an increasing number of patients. It will be imperative for clinicians to identify and circulate their experiences, including both challenges and successes, through their professional practice communities and scholarly publications to foster collaboration and continuously update best practice guidelines for blinatumomab administration.

IMPLICATIONS FOR PRACTICE.

• ■ Recognize that although blinatumomab improves outcomes in children with standard-risk B-lineage acute lymphoblastic leukemia (B-ALL), its administration is associated with unique challenges that can affect patients, families, and clinicians.

• ■ Assess patient, family, and institutional characteristics to develop a comprehensive approach to blinatumomab delivery across care settings.

• ■ As blinatumomab transitions into standard-of-care therapy for some children with B-ALL, continue to update expert recommendations regarding best practices for blinatumomab administration.