Central Infusion Research Articles

1015. Real World Use of Dalbavancin and Oritavancin for Optimized Outpatient Antimicrobial Therapy in Patients Inappropriate for Standard Therapy

Abstract Background Dalbavancin and oritavancin are long acting lipoglycopeptide antibiotics (LaLGP) approved for treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive organisms. These antibiotics have shown promise in treatment of non-FDA approved gram-positive infections including bacteremia, endocarditis, pneumonia, and osteomyelitis. The aim of this review was to determine indication, length of therapy, treatment failures, and adverse drug events (ADE) in patients receiving LaLGP at our institution. Methods Retrospective study of adult patients that received LaLGP within an integrated health system consisting of 3 hospitals and 2 outpatient infusion centers, between July 2016 and February 2022. Data collection included dosing regimen specifics for both LaLGP and non-LaLGP, indication and justification for LaLGP use, culture results, labs, ADE, incidence of readmission and Emergency (ED)/Urgent Care presentation, and treatment failure defined as readmission or return to the ED/Urgent care within 90 days of therapy completion. Results 36 patients received LaLGP during the study period. A majority of patients received LaLGP for an indication other than ABSSSI (64%)(Table 1). Four patients were lost to follow-up but included in analysis of indication and justification for LaLGP use. Staphylococcus aureus (30% MRSA, 26% MSSA) was the most commonly identified pathogen in patients who received LaLGP for non-ABSSSI indications. Justification for use of LaLGP over standard therapy is shown in Table 2. The median duration of standard therapy prior to transitioning to LaLGP was 7 days. Table 3 shows agent selection, number of doses, and outcomes for ABSSSI indications vs non-ABSSSI indications. ABSSSI patients received a maximum of 2 doses; non-ABSSSI indications received 1-8 doses. Re-admission rates were higher in the ABSSSI group compared to non-ABSSSI while ED/Urgent care presentations were higher in non-ABSSSI indications. Conclusion LaLGP is a viable option for therapy completion after improvement is seen while on standard therapy in patients where daily outpatient antimicrobial therapy is not feasible. While LaLGP is currently only approved for ABSSSI, they appear to be safe and effective for other indications. Disclosures All Authors: No reported disclosures.

674. Successful Management of ESBL Infections in Physician Outpatient Infusion Centers (POICs)

Abstract Background Infections with extended-spectrum β-lactamase (ESBL)-producing pathogens present treatment challenges with higher costs of care. Hospitalized patients (pts) with ESBL infections often require outpatient antimicrobial therapy (OPAT) following discharge. An Infectious Disease (ID) physician can facilitate optimal management in both the inpatient and outpatient setting, particularly when a POIC is an option. The increase of ESBL incidence led us to evaluate management and outcomes of genitourinary (GU) and intra-abdominal infections (IAI), the top two ESBL diagnoses treated in POICs. Methods Records were queried for pts hospitalized with ESBL infection and discharged to a POIC between 2019 and 2020. Primary outcome was completion of OPAT. Non-successful completion was defined as premature discontinuation of OPAT including hospital readmission. Adverse events (AEs) and re-treatment within 30 days were captured. Results A total of 112 pts (mean age: 59±17 years, 50% female) from 14 POICs were identified (93 GU, 19 IAI). Of these, 51% had their first ESBL infection and 52% were community-acquired prior to hospitalization. A total of 38% presented with concomitant bacteremia. ESBL E. coli was the predominant Gram-negative pathogen in both infection types (Table 1). Mean hospital LOS was 6±4 days (5±2 days GU, 11±6 days IAI) followed by 13±9 days of OPAT (12±7 days GU, 16±11 days IAI). Carbapenems were most frequently used as treatment (89% ertapenem, 7% meropenem). Overall, 106 pts (95%) successfully completed OPAT. Six pts (5%) discontinued due to hospital readmission. AEs were reported in 15 pts (13%), the majority of which were mild. Re-treatment in the POIC within 30 days post OPAT completion occurred in 6 GU pts. None were lost to follow-up. Table 1 summarizes primary outcome by clinical characteristics. Both GU and IAI pts had 95% successful OPAT completion. Table 1.Successful and non-successful completion of OPAT in patients with ESBL infections Conclusion Outpatient treatment of ESBL infections in POICs post-hospitalization showed high completion rates with low occurrence of readmissions and re-treatments. Consistent with a rise in ESBL infections, our incidence of community-acquired ESBL infections prior to hospitalization were high at 52%. Once ESBL infections were identified in the hospital, the ID physicians with a POIC rapidly facilitated discharge to OPAT. Disclosures Ramesh V. Nathan, MD, FIDSA, Eli Lilly & Co.: Grant/Research Support Brian S. Metzger, MD, MPH, AbbVie: Advisor/Consultant|Cumberland: Advisor/Consultant Lucinda J. Van Anglen, PharmD, Merck & Co.: Grant/Research Support|Paratek: Grant/Research Support.

1762. A Review of Antibiotic Outcomes Data Utilizing the Multidisciplinary OPTIONS-DC Conference for PWUD

Abstract Background Persons who use drugs (PWUD) admitted for serious infections face many challenges when long courses of intravenous (IV) antibiotics are recommended. OPTIONS-DC is a structured multidisciplinary care conference used to navigate some of these challenges with harm reduction principles to consider patient preferences, decrease length of stay when safe, and support successful completion of antibiotics1. We aimed to describe antibiotic course outcomes 4 years after implementation of OPTIONS-DC. Methods We conducted a retrospective review of patients who had an OPTIONS-DC from February 2018 to February 2022. Any PWUD diagnosed with a serious infection requiring > 2 weeks of IV antibiotic treatment were eligible for an OPTIONS-DC. Data was collected via a REDCap database. R version 3.3.2 (R Core Team, 2016) was used for statistical analysis. Results 144 conferences were included, for 129 unique patients. The mean age was 39.4 with 56.3% being male. The most common infections were bacteremia (52.8%) endocarditis (36.1%), and osteomyelitis (47.9%) with a mean recommended treatment duration of 5.62 weeks (Table 1). 87 (60.4%) patients with any substance use initiated medication assisted therapy (MAT) during admission including 74.5% (79/106) of those with opioid use disorder. 112 (77.8%) antibiotic courses were completed with 71 (63.4%) completed outpatient. Of those who initiated or continued MAT during admission, 83 (74.1%) completed antibiotic therapy. Course completion was similar for those discharged home at 84% (21/25) or to a Skilled Nursing Facility (SNF) 81.8% (9/11). All 18 patients who received antibiotics via home infusion vendor and 17 (81%) via infusion center completed their course. 39 (39.8%) patients received long acting IV antibiotics and 23 (23.5%) received oral antibiotics to complete their course. Average out of hospital antibiotic days for those who completed their course were 30.5. Table 1.OPTIONS-DC Table 1Table 1.OPTIONS-DC Table 1 continued Conclusion The OPTIONS-DC model continues to be a useful tool by incorporating harm reduction principles and patient preferences for PWUD at our hospital. Our completion rate of 77.8% and outpatient completion rate of 63.4% are higher while the patient directed discharge rate of 8.3% is lower than what is generally reported in literature for this population2-5. Disclosures Monica K. Sikka, MD, F2G: Site research investigator.

1006. High Adherence and Cost Savings with Home OPAT Provided through Infectious Disease Physician Office Infusion Centers

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) has been shown to be safe and effective for self-administration but can lead to non-adherence without supervision. A physician office infusion center (POIC) with pharmacy services provides a unique opportunity to impact adherence and OPAT management. Patients (pts) typically come to the POIC weekly for catheter care, laboratory collection, medication pick-up and as needed provider visits. Often, close provider oversight allows for de-escalation of OPAT. We evaluated adherence to therapy, visits and associated cost saving in pts receiving self-administered OPAT through POICs. Methods Pts receiving home OPAT in 2021 were randomly selected from participating sites based on annual pt volume. Adherence was assessed as % of OPAT doses dispensed vs. doses missed. Frequency of office visits for routine catheter care and labs along with OPAT completion were collected. Cost savings were calculated in days of OPAT saved due to therapy de-escalation and response to therapy, based upon published daily costs of OPAT. Pt characteristics, OPAT duration, infection type and regimen were captured. Results A total of 125 of 2180 pts from 13 POICs nationally were included (mean age 50±18 years, 52% male). Mean OPAT duration was 38±9 days. Predominant infections were bone and joint (38%), complicated skin (18%), intra-abdominal (15%) and bacteremia (14%). The most common antimicrobials were cephalosporins (54%) with 20 pts self-administering ≥2 drugs. Pts had a mean of 6±3 POIC visits during the therapy course with completion as scheduled in 703/706 visits (99.6%). OPAT was completed as planned in 118 pts (94%), with discontinuations for adverse events (n=3), hospitalization (n=2), or non-adherence (n=2). Overall adherence rate was 99.3% with 51 missed of 7315 doses dispensed. De-escalation during OPAT saved 533 doses equating to 307 days of OPAT (2.4 days/pt). Based on an average daily OPAT cost of $140, this saved $42,980 in the randomized cohort and an estimated $749,571 annually in the entire population. Conclusion Home OPAT through an ID POIC was associated with a very high rate of adherence and compliance to scheduled visits in pts. ID oversight resulted in healthcare cost savings through onsite antimicrobial stewardship and therapy management. Disclosures Lucinda J. Van Anglen, PharmD, Merck & Co.: Grant/Research Support|Paratek: Grant/Research Support.

996. Assessment of First-Dose Antimicrobial Infusion Reactions in Outpatient Parenteral Antimicrobial Therapy (OPAT) Service Patients

Abstract Background The 2018 Infectious Diseases Society of America (IDSA) OPAT guidelines recommend that an outpatient-initiated first dose may be administered at home under the supervision of healthcare personnel who are trained to respond to IgE-mediated hypersensitivity reactions. This may involve a home health nurse, but if resources are limited, agencies may require a first-dose infusion to be completed in a monitored healthcare setting. The objective of this study is to assess the incidence of immediate reactions in UVA OPAT patients who received a supervised outpatient first-dose infusion as part of care for long term antimicrobial management. Methods This single center, retrospective case series evaluated adult patients enrolled in the UVA OPAT program who received a first-dose antimicrobial infusion for initiation of or change in IV antimicrobial therapy at a UVA-affiliated infusion center between January 2019 and October 2021. The primary endpoint is the percentage of UVA OPAT patients who experienced an immediate reaction, which includes IgE-mediated and infusion-related reactions, after receiving a supervised first-dose infusion outpatient. Secondary endpoints include the percentage of UVA OPAT patients who previously received the same antimicrobial and timing of receipt in patients who experienced an immediate reaction and in those who tolerated the first-dose antimicrobial infusion. Data were analyzed using descriptive statistics. Results There were 93 OPAT patients who received 115 first-dose infusions during the study timeframe. Daptomycin, ceftriaxone, and vancomycin accounted for 64% of first-dose infusions. Six patients (6%) experienced an immediate reaction, which included itching, erythema, and nausea. All patients received treatment for their reaction and were able to complete their infusion. Two patients who experienced an immediate reaction had received the same antimicrobial more than 12 months prior. Conclusion After receiving a first-dose antimicrobial infusion, few UVA OPAT patients experienced an immediate reaction, none of which were consistent with IgE-mediated reactions. These findings support the IDSA guidelines recommending a monitored first-dose infusion at home, particularly among those who recently tolerated the same agent. Disclosures All Authors: No reported disclosures.

Patients, family members and healthcare professionals’ top ten research priorities for adults receiving home parenteral nutrition for malignant or benign disease

Home parenteral nutrition (HPN) is the primary treatment for chronic intestinal failure (CIF) due to non-malignant disease and is increasingly used in patients with a diagnosis of cancer. This project engaged with patients, family members and healthcare professionals to ascertain what questions they want researched. This study followed the five-stage process of the James Lind Alliance that involved (1) setting up a steering group, (2) carrying out an initial survey to gather participants' questions, (3) data processing, (4) an interim priority setting survey and (5) final priority setting workshop. Surveys were translated and back translated into Italian, Danish and French. The project was delivered by an international steering committee with representation from Denmark, Italy, the United Kingdom and United States consisting of three patients, six healthcare professionals and facilitated by University researchers. For the first survey, 633 questions were submitted by 292 respondents from 12 countries. There were 79 questions removed as out of scope or already in the published literature. Responses were collated into two interim surveys of 41 questions for benign CIF and 13 questions for HPN and cancer. In the second survey, 216 respondents prioritised their top ten questions. The ordering from the cancer and HPN survey was taken as definitive; top priorities were quality of life, survival, when to commence HPN, using HPN with anti-cancer treatments, access barriers, measuring benefit and ethical implications. For CIF with benign disease, 18 questions were discussed in two workshops attended by 13 patients and 7 healthcare professionals. The questions were ranked using a modified nominal group technique; the top research priorities were prevention and treatment of liver disease, improving central infusion lines, oral absorption, avoiding long-term negative consequences, vascular access, side effects, line infections, decreasing stoma output, quality of life and sleep. Priorities identified will assist researchers to focus on research questions important to patients, family members and healthcare professionals.

Impact of the COVID-19 pandemic on the routine of an infusion center of immunobiologicals from a Brazilian University Hospital.

Impact of the COVID-19 pandemic on the routine of an infusion center of immunobiologicals from a Brazilian University Hospital.

S49 Insurance Delays Biologic Treatment of Pediatric IBD in Tertiary Care Center

Background: Use of biologic medications, such as anti-TNF inhibitors, anti-integrins, and anti-IL-12/23s, for treating pediatric inflammatory bowel disease (IBD) has shown great success in controlling disease and inducing remission. They are often now the therapy of choice in pediatric IBD with evidence of enhanced utility when used early in the disease course. However, the process to get a biologic medication approved for IBD, particularly in pediatrics where FDA approvals lag, is often lengthy and delayed due in large part to the insurance pre-authorization process. While others have reported on insurance delays, it has not been well described how delays are associated with drug choice, payor, past drug failures, and year of initiation. Methods: Patients under 22 years of age at biologic order date were included from a Prospective BioBank Program, which includes longitudinal, clinical patient data, at the IBD Center and Infusion Center of a large, US tertiary care center from 2014-2022. Biologic medications with at least one infusion treatment were considered (infliximab and biosimilars, ustekinumab, vedolizumab). Biologic order date, first infusion date, and insurance at infusion time were recorded. Available prior biologic failures at time of order were also recorded. Results: Data from 211 infusion biologic orders (with known order and initiation date) was recorded, representing 158 individual patients (105 CD, 45 UC, 5 IBD-U; median age at biologic order = 15.12 years). There was a mean delay of 20 days (median = 15, IQR = 16) between medication order and first treatment infusion. Patients ordered ustekinumab (n = 86) experienced significantly more delays of greater than 2 weeks to first infusion than patients ordered infliximab (n = 81, P = 0.0044) or vedolizumab (n = 44, P = 0.035). Though limited sample size, patients with public insurance (n = 8) experienced a similar proportion of delays greater than 2 weeks as patients with private insurance (n = 151) (62.5% and 60%, respectively). There was no significant difference in delay when comparing patient health insurance company at time of infusion (Aetna, n = 23; Cigna, n = 23; Empire Bluecross Blueshield, n = 35; Oxford, n = 20; and United Healthcare n = 33). Over half (57%) of patients with a previously-failed biologic of known order-to-infusion delay time (n = 45) had a greater delay to get their second biologic than their previous biologic. Delays of greater than 2 weeks to first infusion were significantly more likely for biologics ordered 2018-2022 (n = 135) than biologics ordered 2014-2018 (n = 76, P = 0.0049). Conclusion(s): Long delays to receive crucial medication are commonplace in IBD in the US. Documentation of prior failures is often required to achieve approval, but history of prior failures lengthened the approval process. Though biologic treatments have advanced and shown success over the time period considered, patients were more likely to experience lengthy delays to treatment in more recent years. While insurance type and company do not seem to play an important role in treatment delay, biologic choice does. Further research is required to explore how delays may influence physician biologic selection and hinder attempts at precision therapy.

A Nurse-Led Education Intervention to Improve Infusion Center Management of Sickle Cell Pain

Problem Statement: Patients with Sickle Cell Disease (SCD) experience acute pain episodes for which they seek care in the Emergency Department (ED). SCD predominantly affects African Americans, and adults with SCD face significant disparities and bias when seeking care in the ED (Haywood, et al., 2013; Mills, et al. 2011). In January 2019, the UCSD Sickle Cell team established a same-day infusion center (IC) management strategy for SCD pain crises as an alternative strategy to seeking care in the ED. This program was well accepted by patients, and as the IC volume of sickle cell patient visits grew (270 visits in the two years pre-IC vs.1076 visits in two years post-IC), a need was identified to assess and improve IC staff knowledge and comfort of management of sickle cell pain. Methods: A 30-minute educational presentation (EP) was created and delivered in a hybrid (in-person/virtual) format to IC staff at three IC sites. A 9-question Google Forms survey was created with input from a validated survey tool and administered. This form comprised of 7 knowledge questions and 2 questions related to comfort levels assessing pain and administering pain interventions in persons with SCD. Responses were collected pre- and post-EP at 1-week (0-7 days). Results: Forty-three pre-surveys were recorded, and twenty-two post-surveys were returned. The overall average score of correct knowledge-based questions (7 total) increased from 2.98 to 5.18. The total responses of "Comfortable" and "Very comfortable" increased for both comfort level assessing pain in persons with SCD (40.4% pre-EP to 86.4% post-EP), and comfort level administering pain interventions in persons with SCD (47.5% pre-EP to 91% post-EP). Conclusion: Surveys confirm that knowledge deficits and comfort level gaps exist among IC staff. A nurse-led education intervention proves effective in increasing IC staff knowledge and comfort levels treating sickle cell pain in the IC setting. Implementing an education intervention to increase IC staff knowledge about SCD creates an opportunity to optimize IC staff competence and comfort in treating patients with SCD. This education is critical for compassionate care of this vulnerable population and transcending racial bias and disparities.

Progress: Responsiveness Validation of an Electronic Patient Reported Outcome (ePRO) in Adults with Sickle Cell Disease (NCT05407805)

Background: Vaso-occlusive painful crises (VOC) are a hallmark of sickle cell disease (SCD). Historically, efficacy of drugs intended to reduce frequency of VOCs has been evaluated solely on the frequency of VOC that require a medical intervention, such as a visit to the emergency department, an infusion center and/or hospitalization. Several studies (PiSCES, ELIPSIS) have now demonstrated that the majority of painful events are managed in the home setting.1,2 Therefore, accepted measures to evaluate disease burden do not represent the totality of the patient VOC experience. There is a need to improve and expand on existing clinical trial endpoints to capture the totality of the VOC experience. Moreover, participation in clinical trials for patients with SCD faces numerous barriers, such as transportation difficulties, burden to patient's family/work time and recently, concerns about Covid-19 exposure. We aim to quantify daily pain episodes and provide additional evidence supporting validation of responsiveness in a therapeutic setting for a novel SCD electronic patient reported outcomes (ePRO), that may be utilized in a decentralized or traditional study setting. To successfully assess this tool, it is essential that participants comply with the completion of this daily diary. Methods: PROGRESS (NCT05407805) is a prospective study characterizing VOCs in 2 cohorts of patients with HbS/S or S/B0 Thal ≥18 years of age. Group 1, "control" consists of up to 100 patients not on disease modifiers, and group 2," Hydroxyurea" (HU) includes 50 patients on a stable dose of HU. On Day 1, patients have a blood draw for biomarker evaluation and receive training for their SCD diary on an ePRO device. Patient's participation is approximately 7 months. The blood draw and the training on the SCD ePRO device may be performed remotely by a phlebotomist in the patients' home, or at a site. The SCD ePRO diary consists of up to 6 questions and is completed in the evening to reflect the past 24 hours. Strategies to assure the diary is completed include simplification of questions and responses, device alarms, allowance to complete until noon the following day, morning calls to patients if a diary has not been completed the night before and remuneration for the completion of the diary each day. A small bonus payment is provided when 6 or more diaries are completed over a 7-day period, with the bonus increasing during the final 3 months of the study. Results: To date, two sites have screened 15 individuals and enrolled 10 participants. Participants are generally able to complete the diary in approximately 1-2 minutes and the daily diary completion compliance is ~95% over an average of 75 days (range: 9 to 146 days). Discussion: Classical methods for measuring the rate of VOCs, based solely on utilization of medical resources, vastly underestimate the pain burden in SCD; therefore, developing new validated endpoints that measure the totality of pain episodes, including home VOCs is a priority. Demonstration of sustained compliance and responsiveness of a daily diary may provide additional confidence in the use of this tool as an endpoint in broader therapeutic settings.

Fe-Armacist Run Iron Deficiency Management Clinic to Optimize Intravenous Iron Infusions in an Ambulatory Oncology Clinic

Background At Boston Medical Center, patients across disciplines requiring IV iron are referred to a hematologist in the oncology infusion center. The high demand for patient appointments resulted in wait times up to 8 weeks from referral to visit across all hematologic indications. In addition, the absence of a standardized procedure led to increased drug denials, lack of reimbursement, treatment delays, and increased chair time. Pharmacist run clinics are becoming increasingly common and have offset time for general practitioners, improve access, and increase patient satisfaction. This quality improvement (QI) project aimed to increase the number of patients with iron deficiency anemia (IDA) managed by a pharmacist to improve physician access. Methods Patients 18 years of age and older requiring IV iron for IDA were referred for management under a pharmacy run protocol in an outpatient clinic. Providers placed referrals through the electronic medical record (EMR), Epic, that were reviewed daily by pharmacists. Key inclusion criteria were established IDA inadequately controlled by oral iron due to poor absorption, inability to take oral iron, or requirement of rapid replenishment of iron stores. Under a scope of practice with hematologists, pharmacists assessed symptoms of IDA, ordered and interpreted iron laboratory results, selected appropriate IV iron formulation, created a treatment plan within the EMR, and scheduled follow-up. A standard operating procedure (SOP) was developed outlining a treatment algorithm with all available IV iron. Standard documentation was utilized and documented in the hospital EMR for each visit. Per the IHI model, Plan-Do-Study-Act (PDSA) cycles were implemented to assess change over time. PDSA cycle 1 was implementation of a pilot clinic for referrals restricted to hematologists. Outcome measures included total number of referred patients and provider time offset. Process metrics included percentage of visits with appropriate labs as outlined in the SOP. Balancing metrics included number of infusion-related reactions, incidence of hypophosphatemia, and number of pharmacist hours. Results A total of 109 patients were referred to the pharmacy service from February 1, 2022 through June 17, 2022. Of 109 patients referred, 101 (92.6%) patients met inclusion criteria with an average of 5 patients referred weekly (Figure 1). Eight patients (7.3%) were excluded due to: complicated IDA that required further physician workup (4/8, 50%), the need to establish hematology care per the pilot protocol (2/8, 25%), adequate control on oral iron without previous IV therapy (1/8, 12.5%), or the absence of IDA (1, 12.5%). By June 17th, a total of 36 patients (35.6%) had an encounter with a pharmacist. The remaining patients (N=65) received an iron infusion at time of referral and did not require immediate follow-up. Time to next available appointment for patients requiring IV iron was < 7 days. Of patients seen by a pharmacist (N=36), 100% of patients had all per protocol iron studies completed. Six (16%) patients had phosphorus collected during their visit. Hypophosphatemia (phosphate < 2.7 mg/dL) was reported in 3 patients at time of initial pharmacist visit. There were no infusion-related reactions reported or documented in the patients evaluated. The total time spent by a pharmacist on all aspects of the protocol was 51.7 hours since clinic go-live for an average of 2.6 hours per week. More than 150 visits were projected to offset provider visits within 6 months based on the return to clinic time at referral, with a large majority of patients requiring follow-up at 6 months (37%, 37/101) or 3 months (33%, 33/101) (figure 2). Using the average reimbursement for an ambulatory oncology pharmacist visit, it was projected that this service would generate approximately $22,200 in visit revenue during the 6-month time period. Conclusion The pharmacist driven iron clinic was successfully implemented in our ambulatory infusion center. Pharmacists served as an ancillary service under a scope of practice to help improve clinic efficiency by standardizing IV iron and facilitating timely access for patients requiring treatment. Planned PDSA cycles include expansion of referring providers to general internal medicine practitioners. This QI project will continue to streamline workflow for patients with IDA and will aid in future development of similar pharmacist driven practices. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety of Subcutaneous Daratumumab/ Hyaluronidase after Intravenous Daratumumab for Patients with Multiple Myeloma

Monoclonal antibodies targeting CD38 (i.e., daratumumab and isatuximab) are emerging as mainstay of therapy for upfront as well as relapsed multiple myeloma (MM). These antibodies not only target CD38 on myeloma cells but also attach to CD38 antigens on non-hematopoietic tissue such as the bronchial tree causing potential Administration Adverse Reactions (AAR) during infusion/injection. This side effect is mostly explained by activation of CD38/cyclic ADP ribose (cADPR) systems contributing to airway smooth muscle tone and asthma-like symptoms (Malavasi, F, et al. Physiol Rev. 2008). After saturation of bronchial CD38 antigens, the chance of bronchospasm substantially decreases with subsequent doses. Daratumumab and hyaluronidase (DARA SC) is a subcutaneous injection approved in May 2020 for the treatment of multiple myeloma (MM). Efficacy and safety of DARA SC has been established. While clinical trials demonstrated a reduced rate of AAR with DARA SC compared to daratumumab intravenous (DARA IV), there is limited data published regarding safety of switching between the SC and IV formulation . The objective of this research was to evaluate AAR rates when switching from DARA IV to DARA SC at a tertiary medical center. Methods: From May 1, 2020 through May 1, 2022, adult patients with MM who received DARA IV prior to DARA SC were identified through the electronic medical record a single comprehensive cancer center. The supportive medication to mitigate the AAR was the same for both preparation (acetaminophen, Diphenhydramine, corticosteroids and montelukast for patients with history of COPD or asthma). The observation for first dose of DARA SC was 6 hours as standard of care. The primary endpoint of the study was to evaluate the incidence of AAR when switching from DARA IV to DARA SC. Results: 118 patients received DARA SC for treatment of MM were identified, and of those 36 patients switched from DARA IV to DARA SC. The median patient age was 70 years (range: 42-90) with majority of patients being male, N: 25 (69%). Twenty patients had Ig G MM (55%), 10 patients with Ig A (27%) and the rest, N: 6, were light chain MM (16%). The median time from the last dose of DARA IV to the first dose of DARA SC was 28 days (range:3-448). The distribution of patients based on the time interval between IV and SC preparation and AAR is shown in Figure-1. We did not detect any AAR except one patient who had grade II AAR (Erythema Face, Fever, Nausea/Vomiting, Rigors) occurred 3 hours and 36 minutes after administration of DARA SC. This patient received DARA SC 448 days after stopping DARA IV; the AARs were managed medically and patient was discharged to home and tolerated second as well as third dose without any AAR. No one else in the study cohort had any AAR to second or third dose of DARA SC. Conclusion: A low AAR rate was observed when switching from DARA IV to DARA SC in patients being treated for MM. Our results shows no AAR by transitioning from DARA IV to SC if the time interval between the two is less than a year. Therefore, the monitoring times following first dose DARA SC after receiving DARA IV may be able to be shortened in order to increase efficiency in the infusion center and decrease chair time for patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Consolidation of High-Risk Acute Promyelocytic Leukemia (APL) in Community Infusion Centers: A Single Center Experience

Intro: APL is one of the most curable forms of acute myeloid leukemia. Whereas all-trans retinoid acid (ATRA) and arsenic trioxide (ATO) are the standard of care for treatment of low/intermediate risk APL (APL0406 trial, LoCoco et al. NEJM 2013), the optimal treatment of high-risk APL remains unclear. In our institution, we use the APML4 regimen (Iland et al. Blood 2012) to treat high-risk APL patients, which uses idarubicin+ATRA followed by ATRA+ATO for induction. Then, there are two consolidation cycles of ATRA+ATO, the first of which is 28 consecutive days of treatment. Consolidation is followed by two years of ATRA + 6-mercaptopurine + methotrexate maintenance (PETHEMA LPA99, Sanz et al. Blood 2003). In the APML4 trial, the outcomes were excellent for all risk groups, particularly for high-risk patients. However, this regimen cannot be administered in community infusion centers (CIC) that are not open on weekends. In addition, the expertise required to give maintenance therapy makes it challenging to administer outside of an academic medical center. Here, we examine outcomes of high-risk APL patients who received induction at our institution to document the types of consolidation regimens they received and their outcomes. In particular, we focus on the outcomes of high-risk APL patients who received induction with idarubicin+ATRA+ATO (as per APML4) at our institution, and then for practical considerations received consolidation with ATRA+ATO (as per APL0406) in the community. Methods: We performed a retrospective analysis of all patients between the ages of 18-89 who were diagnosed with high-risk APL at the Knight Cancer Institute between January 2009 and July 2022. We identified 19 patients with the diagnosis of high-risk APL. One patient died soon after diagnosis due to intracranial bleed (excluded from final analysis). The remainder completed induction and consolidation. Result: Table 1 shows the main clinical features at diagnosis. The most common complications during induction were differentiation syndrome and coagulopathy. All 18 patients achieved complete morphologic remission (CR) at the end of induction but still had detectable PML-RARA by PCR. 4/18 (22%) patients received the APL2000 regimen (Adès et al. JCO 2006), and 1/18 (6%) patient received the PETHEMA regimen (Sanz et al. Blood 2003). All 5 patients were hospitalized for neutropenic fever, which required significant dose reduction and treatment delay. One patient (6%) received induction with ATRA+ATO+gemtuzumab ozogamicin followed by consolidation with ATRA+ATO (Estey et al. Blood 2006). The majority of patients (12/18, 67%) received induction as per APML4 protocol (Table 2). The APL0406 regimen was administered as consolidation in 11/18 (61%) patients; and all patients except one received consolidation at local CIC. Common side effects were headache and nausea, leading to dose reduction in five patients. One patient continued with APML4 consolidation. Molecular CR was confirmed in all patients at the end of consolidation treatment. 13/18 (72%) patients did not receive maintenance therapy after consolidation. All patients were subsequently followed by RT-PCR for PML/RARA for molecular relapse. At the last follow up, all 18 patients remained to be in molecular CR with no relapsed disease. Discussion: The benefit of ATRA+ATO for low/intermediate risk APL patients is well established, but the optimal management of high-risk APL remains a challenge, especially when consolidation is given in CIC. Our series of patients provides real world evidence that ATRA+ATO consolidation as per APL0406 regimen is effective in high-risk APL patients after induction with idarubicin+ATRA+ATO as per the APML4 regimen. Although the numbers are limited, all patients remain in molecular remission as measured from the end of consolidation, similar to the excellent outcomes of low/intermediate risk APL patients. Consolidation was well tolerated, with minimal treatment delays, suggesting that a standard consolidation regimen for low-, intermediate-, and high-risk APL patients can be successfully administered in the community (most centers typically treat 1-2 patients per year with APL). The majority of patients did not receive maintenance therapy but remained in remission, providing further evidence that maintenance therapy is unnecessary with sufficient ATRA+ATO consolidation, and simplifying therapy (Shah et al. Blood 2018). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Landscape of Maintenance Therapy Trials Following Autologous Transplant for Multiple Myeloma

BACKGROUND: The current standard for maintenance therapy following autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) is lenalidomide, an oral treatment with demonstrated overall survival benefit. Other options for MM may incur toxicities or require frequent visits to infusion centers and may thus not be best suited as maintenance. Patients with high-risk cytogenetic features have poorer outcomes than those considered to have standard risk disease, and national guidelines recommend doublet maintenance (with a proteasome inhibitor and lenalidomide in this setting). Currently, the role of minimal residual disease (MRD) in treatment decision making is unknown but MRD status in this setting may dictate treatment discontinuation in the future. We conducted a review of currently enrolling clinical trials to characterize therapeutic agents/strategies being used or evaluated in a maintenance setting, outcomes evaluated, the inclusion of high-risk patients, and the use of MRD response in guiding management decisions. METHODS: A comprehensive search was performed on the clinicaltrials.gov, clinicaltrialsregister.eu, and anzctr.org.au databases on March 2, 2022, using the keywords "newly diagnosed multiple myeloma", "transplant eligible multiple myeloma", and "maintenance in multiple myeloma". Only studies that were currently recruiting patients, or those listed as active but not yet recruiting were included. Studies that completed enrollment, were terminated, or had been presented or published were not included. Studies were included if patients were planned to undergo autologous stem cell transplant after induction therapy followed by maintenance strategy. If at least one arm received post-transplant maintenance therapy, and the maintenance therapy was specified in the trial description, it was included. Trials evaluating maintenance therapy after a salvage transplant or maintenance therapy in non-transplant settings were excluded. RESULTS: A total of 20 studies were analyzed. Table 1 highlights characteristics. Of the 20 studies, 11 (55.0%) were randomized and 9 (45.0%) were non-randomized. Six studies (30.0%) evaluated PFS as a primary outcome, and 2 studies (10.0%) included OS as a primary outcome. Four of the 20 (20.0%) studies included multiple primary endpoints in addition to time to event outcome, while 4 (20.0%) had a time to event outcome as the sole primary outcome being investigated. Of the 11 randomized studies, 2 studies evaluated OS (18.1%) and 5 evaluated PFS (45.5%) as primary endpoint. MRD negativity was included as a primary endpoint in 11 studies (55.0%) and a secondary endpoint in seven (35%). Of the 9 nonrandomized studies, 4 had a primary endpoint of MRD negativity rate (44.4%), 2 (22.2%) had response-based primary outcomes, and one (11.1%) had a time to event primary outcome. Of the total trials, two (10.0%) assessed or mandated discontinuation of maintenance therapy for those achieving MRD negativity. Table 2 describes maintenance regimens utilized. A total of 4 randomized studies assessed comparison of lenalidomide and another agent to lenalidomide alone with a primary endpoint powered for PFS/OS. Only one study limited enrollment to standard risk disease. No studies enrolled only "high-risk" disease. Amongst a total of 19 trials enrolling patients with high-risk disease, eight trials (42.1%) were offering or permitting patients with high-risk disease to receive single agent lenalidomide. CONCLUSION: Our study analyzing the landscape of current maintenance trials demonstrates that there are many promising clinical trial designs that adapt treatment based on the depth of responses and incorporate newer agents with enough statistical power to demonstrate OS advantage. However, there remains room for improvement, as evidenced by trials evaluating drugs with marked toxicity profiles in non-randomized single arm settings, patients with high-risk disease being permitted to receive treatment that may be inferior to what current guidelines recommend, and a lack of patient centered endpoints (such as OS or quality of life) being evaluated as primary endpoints. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Iron Infusions, Their Reactions and Efficacy Related to Dosing - a Single Center Retrospective Study

Background: Intravenous (IV) iron infusions are associated with a variety of adverse drug reactions (ADRs) including anaphylactic reactions. The Commonly used IV iron formulations are Iron sucrose (Venofer), Ferric carboxymaltose (Injectafer), Sodium ferric gluconate complex (Ferrlecit), and others. Iron sucrose has been approved by the FDA (Food and Drug Administration) for patients with iron deficiency who also have kidney disease. It is also often used off-label for iron deficiency anemia on its own. In our facility, multiple ADRs were noted with Venofer compared to other formulations. Hence, we aimed to study: 1. If altering the dose of Venofer will result in a lesser incidence of allergic reactions. 2. To determine if one preparation of IV iron has a higher incidence of adverse events than another. 3. To evaluate the efficacy after 6 to 8 weeks of completion of iron infusions, by comparing the response to various dosages and formulations. Methods: This is a retrospective chart review of 274 patients ages 18-92 who received at least one dose of Intravenous Iron at Einstein Medical Center Montgomery Outpatient Infusion Center from 01/01/21 to 10/31/21. Patients were divided into two groups based on the Venofer dosing schedule. Group D1 included patients that received any IV iron formulation from January to May 2021. In this group, Venofer dosing was 400mg x 1 followed by 300mg x2. Multiple ADRs were noticed in group D1 hence Group D2 was created. This group included patients that received any IV iron formulation from June to October 2021, where Venofer dosing was changed to 300mg x 3 doses or 300mg x 2 followed by 400mg. We collected data on age, gender, race, preparation, strength, pregnancy status, prior history of allergies and transfusion reactions, adverse drug reactions, the timing of reaction, total doses received, pre/post-medications provided to prevent or treat a reaction, outcomes of reaction, hemoglobin, iron studies before and after the infusions. Patient characteristics in both D1 and D2 groups were well balanced. Data were analyzed and summarized in descriptive measures. Efficacy of intravenous iron treatment was measured as a rise in Hemoglobin by 2gm/dl. Results: Out of 120 patients in group D1, 71 patients (59.2%) received Injectafer, out of these, 12 patients (16.9%) had ADRs, the most common reaction was hypotension, and 1 patient had an anaphylactic reaction requiring Emergency Room (ER) visit. Responders in this group were 28/71(39.4%). 10/71 (14.1%) were lost to follow-up. 48 patients (40%) received Venofer, out of which 11 patients (22.9%) had ADRs, the most common being pain in the back, and 2 patients required ER visits. Responders to the infusion in this group were 11/48 (22.9%) with 10/48 (20%) lost to follow-up. 1 patient (0.8%) received ferumoxytol, with no ADRs to report. In the D2 group, which involved a total of 154 patients, 76 patients (49.3%) received Injectafer, out of which 14 patients (18.4%) had ADRs, again the most common being hypotension, and 2 patients required an ER visit. Responders in this group were 29/76 (38.1%) and 10/76 (13.2%) were lost to follow-up. 77 patients (50%) received Venofer, out of which 9 patients (11.7%) had ADRs, the most common being hypotension and this group has not had any ER visits. Responders to the infusion in this group were 36/77(46.8%) and 9/77 (11.7%) were lost to follow-up. 1 patient (0.6%) received Ferumoxytol with no ADRs. [See Table 1]. Conclusions: Injectafer was overall the most used iron formulation in our institution. It was associated with more ADRs when compared to Venofer, including anaphylactic reactions. The most common ADR was hypotension with Injectafer, and back pain with Venofer. We found that Venofer dosing with 400mg x 1 followed by 300mg x2 was associated with the highest incidence of ADRs. Both strategies of Venofer dose modification with 300mg x 3 and schedule modification, 300x 2 followed by 400mg had greater efficacy and lesser frequency of ADRs as compared to Venofer 400mg followed by 300mg x2. Other studies have shown the benefit of Venofer in non-renal disease patients with iron deficiency. Although our study was not planned to demonstrate this outcome, our data may suggest that Venofer is beneficial for this group of patients. This should be looked into with further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Assessment of Emergency Department Care for Patients with Acute Pain Crisis after the Formation of a Multidisciplinary Team

Introduction:American Society of Hematology (ASH) guidelines recommend the rapid evaluation and treatment of patients presenting to the Emergency Department (ED) with pain from an acute vaso-occlusive episode (VOE) related to sickle cell disease (SCD). The treatment of severe pain from VOE in SCD is time dependent and time sensitive. Guidelines recommend that treatment for acute VOE with parental opioid analgesia occurs within 60 minutes of ED registration. With respect to the five-level Emergency Severity Index (ESI) triage tool, in which lower numbers indicate higher acuity, patients with SCD are to be assigned an Emergency Severity Index (ESI) of 2 indicating (a) greater disease burden, and (b) the need for high priority bed assignment. Objectives: We aimed to create a multidisciplinary team of providers to assess and address the existing barriers and facilitators to improving guideline adherence for the management of acute crises in our large academic health system. The primary outcome of this initiative was to improve guideline adherence by ensuring 90% or greater adherence to ESI 2 assignment to acknowledge illness severity as well as timely, within 60-minute opioid analgesia. Methods: In March 2020, we convened a multidisciplinary team of stakeholders to discuss the ED care of patients with SCD presenting with an acute VOE. The group comprises ED and infusion center nurse champions, nurse educators, nurse leaders, hematologists, palliative care specialists, primary care physicians, psychologists, advanced practice providers and other allied health professionals including social work and spiritual care. Initial monthly meetings established recommendations based on national guidelines and discussed interventions to improve guideline adherence including 1. a nursing driven pain management orderset with subcutaneous and intranasal opioids, 2. a best practice alert with the recommended guidelines. We conducted a retrospective review of ED visit data including all patients with a known diagnosis of sickle cell disease presenting to the ED with a chief complaint of acute pain related to VOE from January 2018-February 2020 and March 2020 to March 2022. We compared the before and after intervention using descriptive statistics. Results: Of the 760 unique encounters for acute pain related to sickle cell disease from 2018-2022, 406 visits occurred before the group formation and 354 visits occurred after the group formed. Mean age was 30.5 years (+/- 19.5) in the pre-intervention period compared to the 29.5 years (+/- 18.9) in the post intervention period. The time to the first opioid order placed pre-intervention averaged 53.3 mins (+/- 64.9) was not significantly different compared to the post period 75.2 mins (+/- 125.8; p =0.17). The proportion of patients assigned an ESI 2 changed from 49.3% to 50.5%. Conclusion: While there was a marginal increase in the ESI 2 assignment among SCD patients presenting in acute VOE, there was no significant change in the ED time to first opioid after the formation of a multidisciplinary team.

Identification and reduction of hazardous drug surface contamination through the use of a novel closed-system transfer device coupled with a point-of-care hazardous drug detection system.

Minimizing hazardous drug (HD) contamination is critical for protecting the health of healthcare workers (HCWs) and patients. Alarmingly, widespread HD contamination has been documented across a variety of clinical settings. Quantitative wipe sampling presents significant time and cost barriers, resulting in routine monitoring adherence rates around 25%. Closed-system drug transfer devices (CSTDs) and qualitative point-of-care tests can be implemented to overcome these barriers. In this study, we tested the effects of the BD PhaSeal Optima (Becton, Dickinson and Company), a recently introduced CSTD, on HD contamination at 2 chemotherapy infusion centers. Wipe samples were taken at 29 workstations at each location prior to and a year following CSTD implementation. Additionally, traditional liquid chromatography with mass spectrometry (LCMS/MS) analyses were compared against a novel lateral flow immunoassay HD testing device (BD HD Check; Becton, Dickinson and Company) to determine the validity of the qualitative assay. We found a 46% reduction in HD contamination after incorporating the CSTD into clinical workflows. Across time points and sites, HD contamination reported by the BD HD Check device was 91% accurate against LCMS/MS and 98% accurate within its limits of detection. Collectively, the evaluated CSTD and lateral flow immunoassay device may help to reduce HD contamination and provide real-time measures of contamination, respectively. As part of a multifaceted approach, these devices may help minimize barriers to routine monitoring, ultimately improving the safety of HCWs and patients.

Workflow Improvement after Implementing Remote Blood Allocation Devices at an Academic Medical Center Blood Bank

Abstract Introduction/Objective Patients with hematological cancer routinely receive red blood cell (RBC) transfusions in the outpatient infusion clinical setting as part of their clinical therapy. Typically, RBCs are delivered to the outpatient infusion clinic via the pneumatic tube (P-tube). However, due to the recent expansion of the hospital footprint and the new location of the transfusion services, the P-tube encountered challenges that impacted the reliability of the delivery of RBC, which can delay patient care and affect patient satisfaction. This study’s purpose is to evaluate the pre-and post-implementation of the Haemobank-20 (HB20), remote blood storage and dispensing device, by reviewing the turn-around time (TAT) and the number of orders fulfilled outside of the transfusion service. Methods/Case Report Blood products are stocked to the HB in the infusion center. An electronic transfusion schedule is reviewed the night before scheduled transfusions to ensure appropriate inventory. When a patient is ready for the transfusion, the clinical nurse will use the device to retrieve blood products for the patient from the HB20. The average timed delivery time from the transfusion service to the outpatient infusion center is about 11 minutes. Data was retrospectively gathered from a 10-month interval before and after HB20 implementation to evaluate the number of orders fulfilled by the HB20. Results (if a Case Study enter NA) The HB has helped maintain nurse-to-patient ratios, reduced traffic at the blood bank issue window, and significantly sped up the turnaround time of RBCs from 11 minutes to less than 60 seconds. Before HB implementation, staff at the blood bank received 2853 units of RBCs through the blood bank window. This has been decreased by 61.2 percent to 1136 RBCs. Conclusion Implementing the Haemobank-20 in the outpatient infusion center has successfully reduced the turnaround time and the workload within the Transfusion Services. The current results study demonstrate that the remote blood-release system is safe and helpful in improving the efficiency of blood issue for patients in remote outpatient locations.

Allocating Blood Products During a Time of Remarkable Shortage

Abstract The COVID-19 Pandemic adversely impacted the nation’s blood supply such that blood suppliers could not fill standing orders. To address the dwindling blood supply, the American Red Cross (ARC) implemented daily thresholds, which distributed red blood cells (RBCs) based on clients’ historical blood orders and the ARC’s inventory. The threshold system left the blood bank to devise a process to judiciously allocate the reduced RBC supply across our institution. Herein, we describe an internal RBC utilization audit, the data from which we used to devise an algorithm to predict our ability to meet transfusion requirements for operating room (OR) procedures. An OR adjudication committee used our report to prioritize elective surgical cases taking places the following day. Thirty-one non-consecutive days of blood inventory release slips were reviewed across three months of recent transfusions. Weekdays were disproportionally investigated to predict the blood utilization for days with scheduled OR procedures. For all RBCs released, the blood type requested and the final disposition (transfused vs returned to blood bank) of the units were recorded. Average use was calculated as well as interquartile range (IQR) to account for transfusion variability. Utilization data was then used to develop a worksheet-based tool to predict ability to meet RBC requirements. Overall, the hospital transfused an average of 80 RBC units each weekday (IQR: 64-92 units). Approximately 40% of all requested RBC units were released to the OR. In turn, the OR transfused only 39% of the RBCs released to them, which represented 20% of transfusions hospital-wide. The OR requested an average of 41 RBC units each weekday (IQR: 25-57 units). The OR transfused an average of 16 units of RBCs each weekday (IQR: 9-21 units). The outpatient cancer center infusion clinic used less than 15% of total RBCs. The biggest user of RBCs were inpatients, who were transfused 65% of RBCs during the week and 82% of transfusions during the weekend. These percentages and the average-to-third-quartile range were used to devise a blood allocation algorithm to inform the OR if the blood bank could support anticipated use. The data was also used to devise a blood allocation worksheet for the on-call transfusion medicine physicians to predict our ability to provide adequate blood for emergent, non-elective procedures that require transfusion support such as liver transplants and aortic repairs. The audit of RBC disposition informed blood inventory management practices during a time of remarkable shortage. Within the confines of the threshold system, the transfusion medicine service allocated the expected number of units based on historical request and transfusion data to predict whether inventory levels could support scheduled and nonscheduled OR procedures.

REAL-WORLD UTILIZATION OF IMMUNE GLOBULIN INTRAVENOUS 10% AT PHYSICIAN OFFICE INFUSION CENTERS

<h3>Introduction</h3> Immune Globulin Intravenous (human) 10% liquid (IGIV 10%) was FDA-approved in 2012, voluntarily withdrawn in 2016, and reintroduced in 2019 by a new manufacturer with an optimized manufacturing process. Given the manufacturing process changes and utilization of the product in the US, the assessment of post-marketing clinical experience is warranted. The objective of this study is to evaluate post-marketing tolerability of IVIG 10% in a real-world setting. <h3>Methods</h3> We conducted a retrospective observational review of a random sample of patients who received IGIV 10% from 8/2021-5/2022 at physician office infusion centers (OICs) throughout the US. Study data from electronic medical records included demographics, therapy details, and infusion-related adverse events (AEs). <h3>Results</h3> Twenty-three of 96 IGIV 10% patients were randomly-selected from 9 OICs. The mean age was 74±5.3 years with 78% female. Common comorbidities included hypertension (74%) and gastroesophageal reflux disease (61%). One patient was immune globulin (IG) naïve, and 22 patients (96%) were IG-treatment experienced. Most (91%) had primary immunodeficiencies, with one chronic lymphocytic leukemia and one dermatomyositis. The mean IGIV 10% dose was 432±129.2 infused every three or four weeks. IGIV 10% infusions were titrated over an average of 78±28.8 minutes with an average maximum infusion rate of 154±18.8 mL/hr. During the study, patients received a mean of 7±2 infusions. Of 155 infusions, five AEs were reported (fatigue, headache, nausea, dizziness) during 4 infusions (17%) for an overall AE rate per infusion of 3%. <h3>Conclusions</h3> IGIV 10% was successfully administered to patients in OICs and was well-tolerated over multiple infusions.