Delivery of Care for Pediatric Patients Receiving Blinatumomab: A Children’s Oncology Group Study

Abstract

Background:

Blinatumomab is an immunotherapy agent utilized in pediatric oncology for the treatment of B-lineage Acute Lymphoblastic Leukemia (B-ALL). Administration of blinatumomab, via continuous 28-day infusion cycles, can present multiple decision points and challenges related to patient care. Nurses are at the forefront of coordinating and delivering care for patients receiving blinatumomab.

Objective:

To describe the current state of practice across Children’s Oncology Group (COG) member institutions regarding blinatumomab administration in both inpatient and home/outpatient settings.

Methods:

Between August and December 2021, a cross-sectional survey was utilized to determine current institutional practices related to blinatumomab administration. A single targeted respondent who was actively engaged in coordinating blinatumomab administration completed the survey on behalf of each COG institution.

Results:

Survey participation rate was 78% (150/192). During the first 28-day blinatumomab cycle, 71 institutions (53%) reported patient hospital stays between 73 hours and 7 days; 42 (31%) reported hospital stays ≤72 hours; and only 12 (9%) reported hospitalization for the full 28-day infusion. Small- to medium-sized institutions were more likely to report longer hospitalizations (p=.03). Most blinatumomab administration occurred in the outpatient setting, with low rates of unplanned clinic/emergency room visits.

Conclusions:

The majority of COG institutions have navigated the complex coordination of care required for children to receive blinatumomab at home. Wide variations in practice were noted across institutions.

Implications for Practice:

This study describes current institutional practices surrounding administration of 28-day blinatumomab infusions in children with leukemia and offers a starting point for institutional benchmarking and standardization of practice.

Introduction

Targeted therapies that harness the immune system to treat malignancies have rapidly been incorporated into cancer treatment. Blinatumomab is one such immunotherapy, which has improved outcomes in B-lineage Acute Lymphoblastic Leukemia (B-ALL) in adult and pediatric settings.^1–3 Blinatumomab is a bispecific T-cell engager (BiTE), a single-chain protein with murine anti-CD19 and anti-CD3 antibodies. Blinatumomab exerts its anti-leukemic effects by engaging the patient’s T-cells through CD3 binding to selectively target the CD19 antigen expressed on B-ALL cells.⁴

Recently the Children’s Oncology Group (COG) demonstrated improved overall survival (OS) with the substitution of blinatumomab for standard post reinduction chemotherapy in pediatric patients experiencing first relapse of B-ALL.⁵ Blinatumomab was found to have significantly lower rates of toxicity, notably for infection and sepsis, when compared to chemotherapy.⁵ However, blinatumomab is associated with other unique toxicities including cytokine release syndrome (CRS) and neurotoxicity. Given the success of blinatumomab in relapsed pediatric B-ALL, clinical trials groups are currently studying whether inclusion of blinatumomab in frontline pediatric B-ALL therapy can further reduce the risk of relapse.^6–8

Blinatumomab administration currently requires continuous infusion via a central venous catheter for 28-day cycles. Inpatient administration is strongly recommended for initiation of cycles followed by home administration with outpatient visits for medical assessment and to change the blinatumomab infusion bags. Compared to standard chemotherapy, blinatumomab presents unique health-system challenges related to preparation, administration, toxicity monitoring, and medication error prevention.⁹ Planning and coordinating care requires significant effort by health care providers, especially to support outpatient (i.e., home) administration. Oncology nurses have been described as core team members central to patient care and communication across the continuum of cancer care delivery to patients.¹⁰ Given that blinatumomab is now included in frontline B-ALL protocols, and considering the complexities involved in its delivery, determining optimal administration strategies to minimize the impact on patient and family quality of life during blinatumomab administration is key. However, there are currently no reports, to our knowledge, detailing institutional practices regarding blinatumomab administration in the pediatric oncology setting.

The majority of children and adolescents with cancer, within the United States, will receive care at a COG member institution. Over 200 children’s hospitals across North America, New Zealand and Australia are united as institutional members of COG, a cooperative group, to conduct research specific to children, adolescents and young adults with cancer. Individual institutions can apply to become a COG member institution if they care for this population of patients and meet established membership criteria (i.e. ability to meet set enrollment numbers on clinical trials and other studies, as well as maintaining compliance with protocol specified care).¹¹ Although treatment trials provide criteria for protocol directed therapy, many decisions related to care delivery are still left to the discretion of the treating center. This allows for potential variance in how care may be provided across member institutions.

The purpose of this study was to describe the current state of practice across COG institutions regarding blinatumomab administration in pediatric oncology patients with B-ALL in both the inpatient and outpatient settings. Findings regarding institutional practices and experiences from this study can provide data to begin building consensus for safe and efficient practices that promote quality patient care. A framework for research, Resilience in Individuals and Families Affected by Cancer, is used as an organizing guide for nursing studies conducted in affiliation with COG.^12,13 Theoretically, this current study aligns with the COG Nursing Research Framework as the results may assist institutions with promoting home blinatumomab delivery which, in turn, may decrease illness related distress in children and families caused by prolonged hospitalization.

Methods

A cross sectional survey was used to characterize blinatumomab administration practices at COG institutions across the United States and Canada. Initial survey questions were drafted by study team members, who were COG nurses with clinical research expertise and protocol nurses assigned to COG trials utilizing blinatumomab. Candidate questions were reviewed and edited by a panel of pediatric oncology clinicians (nurses and physicians) considered experts in blinatumomab delivery. Finalized survey questions were entered into a Qualtrics^® platform (Provo, UT).¹⁴ A copy of the survey questions are available (see Appendix).

Eligibility criteria for study participation included: nurse (registered or advance practice; physician if no nurse available), with a minimum of 6 months experience in current role and actively engaged in coordinating blinatumomab administration at a COG institution. To ensure that the correct survey respondent was identified for each institution, we followed a process that was successfully utilized in a prior COG study.¹⁵ In brief, an email was sent to the Responsible Investigator (RI) Nurse listed on the COG member website for each institution (or site principal investigator if no RI nurse), outlining the study and asking for their assistance in identifying the most appropriate respondent to participate in the survey. The identified respondents were then entered into the Qualtrics system which generated an introductory email, including a copy of the study consent, and the survey link. The identified clinicians were asked to confirm review of the consent form and provide consent (yes or no) to the voluntary study. The system also sent two email reminders, approximately 2–3-weeks apart to non-responders. Non-responding institutions also received a personal phone call or email from a study team member to ensure that the study invitation had been received (i.e., not blocked by institutional firewalls). Quick Response (QR) codes were generated and distributed to institutions when firewalls prevented receipt of emails with embedded survey links.

The study was reviewed by the Institutional Review Board (IRB) at Clemson University and deemed exempt. All co-investigators obtained local IRB review before assisting with the study. Survey responses were collected between August 2021 and December 2021. One survey response per COG institution was allowed. The survey respondent was asked to report basic demographic data for themselves and their institution. COG registration data (3 year rolling average of the number of patients registered with COG between 2019–2021) was obtained from the COG Operations Center, through an approved data request process, and utilized as a proxy for institutional size, categorized as small (≤ 20 annual registrations), medium (21–40), large (41– 75) or very large (>75). As the survey items requested information pertaining to both inpatient and outpatient/home practices, the survey respondent was asked to collect and coordinate responses from other units/settings within their institution as needed.

Descriptive statistics were used to summarize survey responses. Chi-square tests were used to determine associations between variables of interest (e.g., institutional size, number of patients treated with blinatumomab, length of hospital inpatient stay during the first blinatumomab cycle). Institutional size categories were combined (small and medium vs. large and very large) for chi-square analysis to minimize small variable counts. A chi-square test of independence was performed to examine the relationship between institution size and the length of hospitalization around the first cycle of blinatumomab.

Results

Survey Population

There were 213 active COG member institutions within the United States and Canada in July 2001. Of these, eligible survey respondents were identified at 192 (90.1%) sites, and 150 of these eligible respondents returned completed surveys (78% response rate) (Figure 1).

Figure 1.

Study Participation Rates.

Characteristics of Survey Respondents

Survey respondents were primarily female (95%), nurses (95%), and 36 to 45 years (32%) of age. Respondents were in their current role an average of 8.6 (range 0.5 – 35) years and had worked in pediatric oncology an average of 17.6 (range, 1.5 – 41) years (Table 1).

Table 1.

Demographics of Respondents and Institutions (n=150)

Characteristics	N (%)
Respondents
Female	142 (95%)
Age (years)
20–35	31 (21%)
36–45	49 (32%)
46–55	39 (26%)
56 or above	31 (21%)
Occupation
Nurse	143 (95%)
Oncologist	8 (5%)
Average (range) time in current role (years)	8.6 (0.5 – 35)
Average (range) time in pediatric oncology (years)	17.6 (1.5 – 41)
Institutions
Geographical Location
United States	137 (91%)
Canada	13 (9%)
Institutional size (based on annual registrations)a
Small (≤20 registrations/year)	49 (33%)
Medium (21–40 registrations/year)	57 (38%)
Large (41–75 registrations/year)	27 (18%)
Very Large (> 75 registrations/year)	17 (11%)
Proportion of non-English speaking families (n=138)
≤ 25%	84 (61%)
26–49%	42 (30%)
≥ 50%	12 (9%)
Number of patients treated with blinatumomabb
> 10	39 (26%)
6–10	32 (21%)
3–5	47 (31%)
1–2	25 (17%)
0	7 (5%)

Abbreviations: COG, Children’s Oncology Group

^aInstitutional size categorized based on average number of annual COG registrations on 3-year rolling average between 2019–2021

^bIncludes all patients treated with blinatumomab at the institution (on and off study) prior to survey completion

Characteristics of Institutions

Institutions were primarily located in the United States (91%) and were categorized by size as small (33%), medium (38%), large (18%) or very large (11%) based on average number of COG annual registrations (Table 1). The proportion of non-English speaking families cared for at COG institutions was ≥ 50% at 9% of institutions, between 26–49% at 30% of institutions, and ≤ 25% of families at 61% of institutions. Institutional experience with blinatumomab administration ranged from more than 10 patients (26% of institutions) to 1 or 2 patients (17% of institutions). Only 5% (n = 7) of institutions reported no experience with blinatumomab. There was a statistically significant association between institutional size and number of patients treated with blinatumomab, with large and very large institutions more likely to have cared for >10 patients receiving blinatumomab (P < .001). The effect size for this finding (φ = .445) is considered medium to large.¹⁶

Inpatient Care

During the first cycle of blinatumomab administration, patients at most institutions (53%) were hospitalized between 73 hours and 7 days, while patients at 31% of institutions were hospitalized ≤ 72 hours (Table 2). Hospital stays during the first blinatumomab cycle were longer at small to medium sized institutions than at larger institutions, X² (2, N = 129) = 7.32, P = .03. All institutions that reported administering the entire 28-day blinatumomab cycle as inpatient therapy (n = 12) were small or medium size.

Table 2.

Characteristics Related to In-patient Care (n=134)

Characteristics	N (%)
Length of Hospitalization (blinatumomab first cycle)
≤ 72 hours	42 (31%)
73 hours – 7 days	71 (53%)
8–27 days	4 (3%)
28 days	12 (9%)
Other (i.e. varies with study status, on or off clinical trial)	5 (4%)
Pharmacist available nights/weekends
Yes	96 (72%)
No	38 (28%)
Process for back-up bag of blinatumomab (i.e. unexpected bag change)
Yes	85 (63%)
No	49 (37%)
Frequency of vital signs (during initial 72 hours, blinatumomab first cycle)
1–2 hours	27 (20%)
4 hours	79 (60%)
Other	3 (20%)
Frequency of neurological checks (during initial 72 hours, blinatumomab first cycle) (n=129)
2 hours	17 (13%)
4 hours	79 (61%)
6–12 hours	16 (12%)
Daily	11 (9%)
Other (only performed if status changes)	6 (5%)
Nurse to patient ratio (during initial 72 hours, blinatumomab first cycle) (n=132)
1:1 (1 nurse per patient)	17 (13%)
1:2	51 (39%)
1:3	44 (33%)
1:4	12 (9%)
Other	8 (6%)
Nurse to patient ratio lower (less patients/nurse) than normal (during initial 72 hours, blinatumomab first cycle)
Yes	68 (51%)
No	66 (49%)
Infusion pumps
Institutions normal in-patient pump	73 (54%)
CADD	56 (42%)
Curlin	4 (3%)
Type varies – dependent on study status (on/off clinical trial)	1 (1%)

Abbreviations: CADD, Continuous Ambulatory Delivery Device

Of the institutions reporting inpatient care practices, 96/134 (72%) had a pharmacist available overnight and on weekends, and 85 (63%) reported having a process in place for obtaining a back-up bag of blinatumomab for unanticipated bag changes (Table 2). During the first 72 hours of the initial blinatumomab cycle, there was variability in the frequency that institutions reported assessment of vital signs or neurological status. The most common interval was every 4 hours for both vital signs (60% of institutions) and neurological assessments (61%). Some institutions assessed vital signs more frequently around infusion startup, then tapered the frequency. Twenty-seven institutions (20%), however, reported vital sign assessment every 1–2 hours during the entire first 72 hours of blinatumomab. The most frequently reported staffing ratio during blinatumomab administration was one nurse for every 2 or 3 patients (n = 95; 72%), with 51% (n = 68) of institutions reporting that the nurse-to-patient staffing ratio during the first 72 hours of a blinatumomab administration was lower than the typical ratio on their units. Standard inpatient institutional infusion pumps were used for blinatumomab delivery at 54% (n = 73) of institutions, while outpatient infusion style pumps (e.g., Continuous Ambulatory Delivery Device [CADD]) were used for inpatient administration at 42% (n = 56) of institutions.

Of the 134 institutions sharing their care delivery practices during inpatient administration of blinatumomab, 31 (23%) reported having no issues with infusion pumps or equipment (Figure 2). The remaining 103 institutions reported at least one pump or equipment related issue. Institutions were allowed to select “all that applied” from a list of anticipated problems or select “other” to describe additional issues. The most frequently reported inpatient pump or equipment issues were: blood backing up in the line (36%), air in line alarm (31%) line break/line leak (21%), resistance alarm (13%), line clotting (9%) and line disconnect or deaccess (3%).

Figure 2.

Commonly Reported Pump or Equipment Issues during Inpatient and Outpatient Blinatumomab Infusions.

Outpatient Care

As most patients were discharged from the hospital during the first week of the 28-day blinatumomab cycle, the majority of care surrounding blinatumomab delivery occurred in the outpatient setting. The term “outpatient” is applied broadly and includes any location (i.e. patient’s home) in which care occurred outside of the inpatient setting. Institutions were asked to share the frequency of unplanned clinic or emergency room visits for blinatumomab-related administration issues. Reported by 126 institutions, unplanned visits were categorized as “never” (7%), “rarely” (55%), “sometimes” (37%), or “often” (1%) (Table 3).

Table 3.

Characteristics of Out-patient Care (n= 126)

Characteristics	N (%)
Home Health Agency Assisted with Care
Yes	43 (34%)
No	83 (66%)
Frequency of unplanned clinic or ER visits related to blinatumomab administration
Never	9 (7%)
Rarely	69 (55%)
Sometimes	47 (37%)
Often	1 (1%)
Infusion pumps
CADD	103 (82%)
Curlin	14 (11%)
Other	9 (7%)
Source of infusion pump for outpatient use
Provided by home health agency	43 (34%)
Loaned from institution	44 (35%)
Rented from durable medical equipment or infusion Company	33 (26%)
Other (i.e. “varies with study enrollment status”)	6 (5%)
Bag Type (in hours of infusion) (n=125)
Only one bag size provided (n=50):	50 (40%)
24 hours	2 (4%)
48 hours	5 (10%)
72 hours	12 (24%)
96 hours	21 (42%)
7 days	10 (20%)
Combination of bag sizes provided (n=75)	75 (60%)
Combinations included 72 or 96 hour bags	59 (79%)
Combinations did not include 72 or 96 hour bags	3 (4%)
Combination unknown (bag size not specified)	13 (17%)

Abbreviations: CADD, Continuous Ambulatory Delivery Device; ER, Emergency Room

Of the institutions that discharged patients to continue blinatumomab infusions at home (n = 126), only 34% (n = 43) utilized a home health agency. When home health agencies were not utilized, institutions reported securing outpatient pumps through rental agreements with other companies (such as durable medical equipment providers), or through institutional purchase of pumps. CADD pumps were utilized for home infusions by 82% (103/126) of facilities.

There was variability in the size of home blinatumomab infusion bags, with 75 (60%) of institutions reporting use of different combinations of bag size (Table 3). For institutions using multiple bag sizes, combinations that included 72- or 96-hour infusion bags were reported by 59 (79%). For the 50 institutions (40%) that utilized only a single bag size, 21 (42%) of these reported 96-hour infusion bags, while only 2 (4%) used 24-hour infusion bag sizes for outpatient administration.

Of the 122 institutions reporting care delivery practices during outpatient administration of blinatumomab, 11 (9%) reported having no issues with infusion pumps or equipment (Figure 2). The remaining 111 institutions reported at least one issue, selecting all applicable items from a list of anticipated problems or selecting “other” and describing the issues that were experienced. The most frequently reported outpatient pump or equipment issues were: line break/line leak (57%), blood backing up in the line (29%), air in line alarm (27%), resistance alarm (23%), line clotting (10%) and line disconnect or deaccess (8%).

Venous Access Lines

As the type of central line can vary with a patient’s treatment plan, the survey asked specifically about the most common central lines utilized for patients enrolled on COG protocol AALL1731 (Table 4) which included a blinatumomab randomization. Of the 143 institutions, central lines included port-a-cath (PORT, 90%), peripherally inserted central catheter (PICC; 7%), and single or double-lumen tunneled central line (3%). Other survey questions pertaining to venous access were not limited to patient enrollment on one specific clinical trial. When reporting practices related to secondary intravenous access devices, in any patient with a PORT receiving blinatumomab, 56 of 134 institutions (42%) shared that a PICC or peripheral intravenous (PIV) access were routinely placed during the first 72 hours of blinatumomab cycle 1. Placing a second IV access device, such as PIV (n = 83; 62%) or PICC (n = 18; 13%), was also common for patients with PORTs requiring sedation for procedures during a blinatumomab cycle. In contrast, 25% (33 of 134) of institutions reported temporarily interrupting the blinatumomab to use the line for administration of sedation. There was no statistically significant association between the institutional size and placement of a second IV access line during the first 72 hours of blinatumomab cycle 1, X² (1, N = 134) = 1.80, P = .19) or between institutional size and placement of a second IV access during procedures requiring sedation, X² (1, N = 134) = .34, P = .67.

Table 4.

Intravenous Access for Blinatumomab Infusion (n=143)

Characteristics	N (%)
Central line typea
PORT	128 (90%)
PICC	10 (7%)
Other (single or double lumen line)	4 (3%)
Unknown	1 (<1%)
Second IV access (PICC or PIV) during first 72 hours of blinatumomab Cycle 1, for patients with PORT (n=134)b
Yes	56 (42%)
No	78 (58%)
Second IV access (PICC or PIV), for patients with PORT, during procedures requiring sedation that occur during blinatumomab cycle (n=134)b
PIV	83 (62%)
PICC	18 (13%)
None – blinatumomab infusion interrupted	33 (25%)

Abbreviations: IV, Intravenous; PICC, Peripherally Inserted Central Catheter; PIV, Peripheral Intravenous; PORT, Port-a-catheter.

^aQuestion specific to the most common central line types utilized for patients enrolled on COG AALL1731.

^bResponses not limited to COG AALL1731 clinical trial enrollments.

Education

To support institutions administering COG protocols containing blinatumomab, an educational resource (Frequently Asked Question [FAQs]) was previously developed by study team members and posted on the COG AALL1731 study page on the COG member website. The majority of institutions (72%) reported being aware of this educational resource. Institutions shared that families primarily received blinatumomab education through informal bedside education provided by clinicians, or through written materials (primarily developed by the institution). Some institutions with higher percentages of non-English speaking families reported working through the process to develop needed patient/family educational materials in other languages.

Discussion

This study reports the collective experiences and practices of institutions related to administration of blinatumomab to patients across COG, a large pediatric clinical trials consortium. Engagement in the survey was high, as evidenced by a 78% survey completion rate, despite survey data being collected during the height of the COVID-19 pandemic. Respondents had an average of 17.5 years of experience working in pediatric oncology, suggesting knowledgeable clinician participation. Additionally, evidence of experience related to caring for pediatric patients receiving blinatumomab was evident, with 47% of respondents reporting that their institution had cared for six or more patients. Our data indicates that most institutions have successfully worked through the complicated care coordination process and have developed practices and policies that support children being discharged home on blinatumomab infusions. Only 9% (n = 12) of institutions reported routinely administering the entire 28-days of a blinatumomab cycle on the inpatient unit.

A very important finding relates to institutions reporting successful outpatient administration of blinatumomab with infrequent infusion-related issues requiring an unplanned clinic or emergency room visit. Additionally, most institutions reported the delivery of blinatumomab without the assistance of a home health agency. Outpatient blinatumomab infusions are important as this can reduce the number of inpatient days and potentially decrease the associated burden for families and improving overall quality of life. To facilitate outpatient delivery of blinatumomab, most institutions reported using a combination of 72 and 96-hour bags sizes, thus requiring two clinic visits per week and avoidance of weekend bag changes. Seven-day bags of blinatumomab are restricted to patients weighing over 22 kg, a weight typically achieved around 6 years of age in an average healthy child. Only 7% of institutions reported experience using 7-day infusion bags for blinatumomab. It is worth noting that the hourly infusion rate for 7-day bag preparations is considerably lower than other preparations, introducing concern for increased risk of line occlusions and dysfunction.

The finding related to increased length of hospital stays surrounding blinatumomab infusions in small to medium size institutions (defined as ≤40 pediatric oncology patient registrations/year through COG) is interesting but the authors are not able to provide rationale for why this occurred. We can speculate that smaller centers may care for a disproportionate number of patients that live in rural settings with limited access to healthcare should an urgent need arise. Additional research is needed to fully understand items that impact hospital stays related to blinatumomab administration.

Our results demonstrate considerable variation in current practices regarding the administration of blinatumomab. One clinically important example is the frequent placement of secondary IV access devices during blinatumomab cycles, in addition to the primary central venous catheter. In early phase clinical trials of blinatumomab, patient safety was a primary outcome of interest, given the concern and unknown risk of blinatumomab-related CRS and neurotoxicity. Therefore, placement of a double lumen central venous catheter was strongly recommended, in these early phase trials, to allow for a dedicated line for blinatumomab administration and access to an alternate lumen for supportive therapies. Importantly, early phase trials reported low rates of significant CRS and neurotoxicity.^1,7 Findings from the phase 3 COG clinical trial ALL1331, which included randomization to post-reinduction blinatumomab for pediatric patients with first relapse of B-ALL, also reported low rates of grade 3 or higher adverse-events specific to blinatumomab during Cycle 1 (CRS [1%], encephalopathy [2%] and seizure [1%]).⁵ Combined, these data support re-evaluating the need for more than one point of IV access, particularly for patients in morphologic remission and/or low disease burden. Our survey revealed that 42% of institutions continue to place an additional line, either a PIV or PICC during the first cycle of blinatumomab for patients with PORTs. Placing additional IV access involves another painful procedure and potentially increases the risk of infection. The benefits and risks of placing a second IV access should therefore be carefully weighed.

Avoidance of line flushing was also recommended during early phase pediatric clinical trials, secondary to concerns that flushing could result in a bolus of blinatumomab potentially increasing risk for CRS. Central line flushing typically involves 1.5 to 3mL of normal saline or heparin, resulting in the patient receiving a bolus of the remaining volume of solution within the line that contains blinatumomab.¹⁷ Line flushing is required to maintain patency and for routine clinical care such as bloodwork and administering other medications.¹⁸ One example is the delivery of care during procedures for intrathecal chemotherapy delivery, a critical component of pediatric B-ALL therapy that requires sedation in most children. Evidence from our survey demonstrates that while 25% of institutions interrupt the blinatumomab infusion to provide sedation for these procedures, the majority still place an additional IV (62% placing a PIV and 13% placing PICC lines) to facilitate administration of intrathecal chemotherapy or other minor procedures (i.e. changing PORT needles). Our findings provide preliminary evidence to suggest that brief interruptions of the blinatumomab infusion, including necessary line flushing, have been reported as current practice at institutions that do not place secondary lines. Although no issues were reported from this practice by survey respondents, additional research is recommended to guide future patient care recommendations.

Caring for patients receiving blinatumomab has unique considerations specific to minimizing interruptions of the infusion to less than one hour when possible. Institutions shared practices that supported this goal, such as developing a back-up plan in case a patient needs an unexpected bag change. Additionally, most institutions indicated that they have a trained pharmacist available overnight and/or on weekends to assist with blinatumomab bag preparation as needed. Having knowledgeable pharmacists available to prepare needed blinatumomab infusion bags can minimize prolonged interruptions and decrease risks for preparation errors.⁹ Variability in inpatient care was observed with the frequency of vital sign and neurological assessments during the first 72 hours of blinatumomab administration. While some institutions utilized more frequent assessments, the most commonly reported frequency was every 4 hours, during the first 72 hours of blinatumomab infusion. Additionally, 50% of institutions indicated that nurse to patient ratios during the first 72 hours of blinatumomab was either 1:1 or 1:2, and that these ratios were lower than usual to allow for more vigilant patient monitoring. Considering the low rates of significant CRS and neurotoxicity during previous clinical trials, an evaluation of current nurse-patient staffing assignments and frequency of patient assessments are needed to reflect both patient safety and staffing resources.

There were notable differences in reported issues with pump or infusion equipment, during blinatumomab administration, between the inpatient and outpatient settings. Infusion line breaks, leaks, disconnections, and accidental central line deaccess were more frequently reported during outpatient infusions when children are more likely to have increased activity. This finding suggests that institutions should provide anticipatory guidance to assist families with implementing preventative actions (i.e. well secured infusion line) while reinforcing the need to quickly notify institutions when emergency visits are warranted to resolve/restart blinatumomab infusions. Families have reported feeling overwhelmed and unprepared to provide care for their child with cancer after the initial hospital discharge.^19,20 The additional layer of complexity surrounding home administration of a continuous infusion may increase family concerns and indicate a greater need for early an on-going patient/family education prior to hospital discharge. The need for patient/family education to be delivered in non-English languages is also a priority consideration, especially for those institutions that provide care to a large proportion of non- English-speaking families. Patient and family education is a high priority for the nursing discipline within COG and this study provides guidance for extending resources specific to blinatumomab.¹²

Limitations and Strengths

Study limitations include lack of data regarding the practices at institutions that did not participate in the survey. Demographic information (location and size of institution) was not explored for non-responding institutions, so we do not know if differences exist between institutions that responded and those that did not. Institutions with more limited blinatumomab use may have been less likely to participate; nevertheless, the survey response rate was high and represented institutions of all sizes from across the United States and Canada. Additionally, it is possible that despite our request for survey participants to solicit input from other individuals at their institutions regarding areas with which the respondent was unfamiliar, this may not have occurred, potentially leading to less accurate information. Additionally, this survey only captures the institutional experience surrounding care for children receiving blinatumomab. We did not capture the experience from the family’s perspective; future studies should determine the full benefits and burdens of delivering continuous blinatumomab infusions at home from the family’s viewpoint. This study has many notable strengths including the high survey response rate (78%), careful targeting of survey respondents (primarily nurses), and questions that sought to gain insight into the practices surrounding blinatumomab delivery in children with cancer.

Conclusion

This study describes the experiences of 150 COG institutions that administered blinatumomab to pediatric patients with B-ALL in the inpatient and outpatient settings. As evidenced by the high response rate of this survey, nurses are intricately involved in delivering and/or coordinating care for patients receiving blinatumomab. The findings presented within this study may be used as a starting point to benchmark individual institutional care against the larger cohort. Furthermore, these findings provide evidence for developing standardized care practices and offer important implications for infusion-related processes in future clinical trials that include blinatumomab.