Rapid Infusion Protocol Research Articles

A Phase II, Open-Label Study of an Accelerated Infusion Rate of Daratumumab in Patients With Relapsed and Refractory Multiple Myeloma.

Daratumumab is an anti-CD38 monoclonal antibody initially approved as a single agent for the treatment of relapsed and refractory multiple myeloma. The infusion-related reactions (IRRs) commonly seen with intravenous daratumumab have been managed by prolonging the first infusion, temporarily stopping/slowing the rate if reactions occur and using adequate pre- and post-infusion medications. Several retrospective studies have evaluated shorter infusions after ≥ 2 prior doses administered at the standard rates. Although the shorter infusions were well-tolerated, patients in these reports were given heterogeneous daratumumab regimens and had often already received multiple doses at the longer standard rates. CMRG-009 is a prospective study designed to demonstrate the safety of accelerated daratumumab infusions commencing with the second dose. After an initial dose on Cycle 1 Day consisting of 8 mg/kg over 4 hours, all subsequent doses were given over 90 minutes. No grade 3 IRRs were observed with the 90-minutes infusions. Both the safety profile and anti-myeloma effects were otherwise similar to those observed with other single agent daratumumab studies using longer infusion times. This is the first formal prospective trial using infusion times shorter than the standard schedule directly after an initial 4-hours dose. This rapid infusion protocol has resulted in more efficient resource utilization and has become the standard protocol for the use in all intravenous daratumumab regimens in Canada. This approach has been particularly helpful in shortening chair time during the COVID-19 pandemic and providing a useful alternative in jurisdictions without access to subcutaneous daratumumab.

Effects of an Ocrevus Rapid Infusion Protocol: A Literature Review and Quality Improvement Project.

The administration of Ocrevus, an infusion therapy for the treatment of multiple sclerosis, is time and labor intensive, leading to poor patient adherence, treatment delays due to scheduling issues, and significant staff workload. This problem worsened during the COVID-19 pandemic, which created scheduling difficulties due to space restrictions. A US Food and Drug Administration-approved rapid infusion protocol for Ocrevus decreases the infusion time by 1.5 hours per patient. The purpose of this project was to complete a literature review on rapid infusion protocols and analyze the effects of the Ocrevus rapid infusion protocol on 2 outcomes of interest: total visit time and infusion reaction rates. Data were collected using retrospective chart review and analyzed by comparing the results of each outcome to the same data points prior to the implementation of the project. Results found a statistically significant decrease in visit time, with no increase in infusion reaction rates. These findings support the implementation of this rapid Ocrevus infusion protocol in the outpatient setting with the potential to improve patient scheduling, patient satisfaction, and nursing workload, while maintaining patient safety.

Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma.

BackgroundThe anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019.MethodsWe conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs.ResultsA total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol.ConclusionsOur findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.

Nine year experience of the Northern Ireland Inherited Cardiac Conditions Service (NI ICC of slow vs. rapid ajmaline infusion protocols for the diagnosis of Brugada syndrome (BrS)

Abstract Background BrS is diagnosed in patients with ST-segment elevation with type1 morphology ≥2mm in one or more leads among the right precordial leads V1 and/or V2 positioned in the second, third or fourth intercostal space, occurring either spontaneously or after provocative drug test with intravenous administration of sodium channel blockers (ie. ajmaline, flecainide, procainamide or pilsicainide). The specific protocol for Ajmaline provocation testing for diagnosis of BrS has been debated between ICC services worldwide. Concerns regarding safety and false positive rates are perceived to be associated with a more rapid infusion protocol. This retrospective observational cohort study describes the safety and positivity rates for patients undergoing ajmaline provocation challenge by both protocols over nine years. Method Consecutive adults undergoing ajmaline challenge test from Mach 2011 to Feb 2020 were retrospectively collected. Data on patient demographics, indication for testing, genetic information, adverse events and positivity rates were compared by test protocol used. Slow protocol was defined as total dose of 1mg/kg ajmaline capped at 100mg given at rate of 10mg/min over 10 minutes. Rapid protocol was defined as 1mg/kg ajmaline capped at 100mg given over 5 minutes. Results A total of 350 ajmaline challenges were included (275 (73%) slow vs. 75 (27%) rapid protocol) [Mean age 40±15 years; 53% male]. Indication for conducting the test was a) Family history of Brugada syndrome 164 (43%) b) Family history of SADS/SUD 103 (28%), c) OOHCA 22 (6%) d) abnormal ECG 39 (11%) and e) syncope 22 (6%). Among the positive test group, average time for test positivity is 5.92 minutes and average dose was 55mgs (p<0.05). There were no differences between positivity rate between the two protocols, group A vs. group B, p=0.45, ns. Comparison between all patients with positive vs. negative results regardless of the protocol, showed no statistical differences. Predominantly male in both groups (p=0.71, ns) and mean age of patients in their 40's (p=0.93, ns). There is a trend that positive patients likely to have family history of BrS p=0.08, ns). 2 patients had experience jaundice at later stage which resolved. Conclusion In NI ICC service to date, we have performed 350 Ajmaline test over the last nine years. Our positivity rate was 21% (75/350). We did not identify any significant evidence of ventricular dysrhythmia (0) or QRS broadening (2) that resulting in early termination of the protocol. Abnormal ECG with absence of symptoms yields low. Therefore we will continue fast protocol in our service for efficiency in our unit. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Belfast Health and Social Care TrustCormac Felowship

Rapid infusion protocol of iron polymaltose saves cost in management of iron deficiency anaemia

Rapid infusion protocol of iron polymaltose saves cost in management of iron deficiency anaemia

A budget impact analysis of iron polymaltose and ferric carboxymaltose infusions

Background In Australia, iron deficiency anaemia can be managed by ferric carboxymaltose, and iron polymaltose given via either a traditional slow or new rapid infusion protocol. These differ in their manufacturing, administration, and monitoring requirements, with unknown associated costs. Aim To compare the direct costs of iron infusions used in Australia; and explore potential savings associated with increased uptake of the least-expensive option at a local hospital. Method A time-motion method was used to determine the labour and consumables associatedwith each infusion protocol. Secondly, a frequency analysis identified the most common iron infusion doses prescribed at the study site. The total direct costs per protocol were compared at these doses and then the potential savings from switching to the lowest-costing of these protocols where possible were explored. Results The most common doses were 0.5g, 1g, 1.5g and 2g. At these dose points, ferric carboxymaltose infusions are the least expensive, but only if national health subsidies are applied. In cases where they do not apply, iron polymaltose prepared from ampoules and infused using the rapid protocol ('Iron Polymaltose Ampoules Rapid') is the least expensive. Switching all applicable ferric carboxymaltose infusions and iron polymaltose infusions administered using the slow infusion protocol to Iron Polymaltose Ampoules Rapid is projected to yield up to $12,000 worth of savings annually. Conclusions Increased use of the Iron Polymaltose Ampoules Rapid protocol when government-subsidised options are not available is projected to have cost-saving outcomes. Investigation of implementation strategies to increase the use of this protocol are warranted.

Assessment Of Hypersensitivity Reactions and Feasibility Of a 60 Minute Rapid Infusion Rituximab Protocol At a Comprehensive Cancer Center

IntroductionRituximab (R) is a chimeric monoclonal antibody with approved indications for non-hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Infusion reactions among patients with NHL are common during the first infusion (incidence of 77%), but decrease with subsequent infusions. Consequently, infusions have been gradually titrated, which may take more than three hours for completion depending on dose and tolerability. However, emerging data suggest that rapid infusion protocols may be safe for patients who receive the first dose with minimal infusion toxicity. MethodsThe purpose of this study was to assess the feasibility of a rapid infusion R protocol in a comprehensive cancer center's outpatient infusion center. The primary outcome measure was the incidence of grade 3 and 4 hypersensitivity reactions during a 60 minute infusion protocol of R in patients with B-cell malignancies. Secondary objective included infusion time savings of a 60 minute infusion of R versus a standard titration schedule, as well as nursing satisfaction. Patients were enrolled in this prospective, single institution, single arm study which was approved by the investigational review board. Inclusion criteria included age >18 years, diagnosis of indolent or intermediate grade B-cell malignancy, second R infusion within 3 months of first infusion, and planned outpatient treatment with a regimen including R therapy at a dose of 375mg/m2. Patients were excluded for diagnosis of an aggressive lymphoma histology, absolute lymphocyte count > 10 x 103/µL, enrollment on another clinical trial, allergy to murine-containing medications, exposure to R (<6 months from first dose) prior to enrollment in this study, or grade 3 or 4 hypersensitivity reaction during first R infusion. All patients received the first dose of R by the standard titration schedule as described in the package insert. The investigational protocol was instituted for the second R administration. The infusion began at 100mg/hr administered over 15 minutes and the remaining dose was given over 45 minutes. All patients received 50mg of oral diphenhydramine and 650mg of oral acetaminophen as premedication. To calculate time savings between rapid infusion and standard titration, each patient served as their own control. Nursing data collection included monitoring vitals every 15 minutes (blood pressure, heart rate, temperature, respiratory rate), start and stop times of R infusion, description and grade of hypersensitivity reactions, administration of rescue medications during infusion, and survey assessment of nursing satisfaction. ResultsFrom October 2010 to April 2013, 52 patients were enrolled to the study. Fifty received rapid infusion over 60 minutes during the second R administration. The 2 patients who did not continue on study were deemed ineligible. Patient 1 expired secondary to disease progression after signing consent and patient 2 experienced a grade 3 reaction following end of first infusion. The median age was 63 years (19-85) with 60% female. Chemotherapy regimens included: R-cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP, n = 19), single-agent R (n = 14), R-bendamustine (BR, n=7), R-cyclophosphamide, vincristine, prednisone (RCVP, n=4), R-gemcitabine, oxaliplatin (RGEMOX, n=3), R-fludarabine, cyclophosphamide (FCR, n=1), R-pentostatin, cyclophosphamide (PCR, n=1) and R-bortezomib (n=1). The rate of infusion related reactions (all grades) observed with the rapid infusion protocol was 0% (1-sided 97.5% CI 0-7.1%). The mean time for the rapid R infusion was 62.4 (95% CI 61.2-63.6) minutes. When compared to the standard second dose infusion recommendations, a mean time of 94.2 (95% 90-98.4) minutes was saved with rapid infusion. Post infusion nursing surveys demonstrated 100% satisfaction with administration of rapid infusion over standard titration practice. ConclusionsA 60 minute rapid rituximab infusion can be safely administered in an outpatient infusion center. The faster infusion allows for less resource utilization and increased nursing satisfaction. Disclosures:No relevant conflicts of interest to declare.

Real-World Utilization and Safety of Daratumumab IV Rapid Infusions Administered in a Community Setting: A Retrospective Observational Study.

BackgroundSome institutions have implemented a daratumumab intravenous rapid-infusion protocol in which patients with multiple myeloma (MM) receive their third and subsequent infusions within ~ 90 min instead of ≥ 3 h.ObjectiveThis study sought to understand the utilization, effectiveness, and infusion reactions (IRs) observed in patients with MM who received daratumumab rapid infusions.MethodsElectronic medical records from Florida Cancer Specialists & Research Institute were used. Adult patients with MM who received one or more rapid daratumumab infusion (full dose in ≤ 110 min) at their third or later infusion of the first daratumumab-containing regimen (index date: 16 November 2015 to 15 March 2019) were included. IRs included events that (1) occurred ≤ 24 h post-daratumumab infusion or (2) were stated as an IR in the patient charts. Non-IR adverse events (AEs) were events attributed to daratumumab in patient charts that did not meet the IR definition.ResultsIn total, 147 patients received one or more rapid infusion in their first daratumumab-containing regimen. Median time from initial MM diagnosis to index date was 2.5 years. Non-IR AEs occurred in 10.2% of patients during treatment, and 36.7% experienced one or more IR after receiving a daratumumab infusion. No IRs occurred after a rapid infusion. The overall response rate was 91.1% (after rapid infusions only: 71.3%).ConclusionsThis study provides real-world evidence on the practice patterns of daratumumab rapid infusions in a large community-based oncology clinic system. These results suggest that treatment regimens including daratumumab rapid infusions at the third infusion or later were well-tolerated, and their effectiveness was comparable to that observed in clinical trials.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-020-00226-3.

Fast and safe: Optimising multiple sclerosis infusions during COVID-19 pandemic

Background: The COVID-19 pandemic challenges multiple sclerosis services to be innovative in delivering infusible therapies. To reduce time in clinical settings, and potential staff or space losses, we implemented rapid infusion protocols for selected patients.Objective: To analyse the rate of infusion related reactions and patient experience of rapid infusions of natalizumab and ocrelizumab. To document time reduction patients spent in clinical settings during the COVID-19 pandemic.Methods: Patients with prior exposure to at least three natalizumab or two 300mg ocrelizumab infusions were approved for rapid protocols. A retrospective audit and survey were completed.Results: We analysed 269 rapid natalizumab infusions and 100 rapid ocrelizumab infusions. Infusion related reactions during the natalizumab or ocrelizumab infusions occurred in two patients (1.52%) and eight patients (8%), respectively. All infusion related reactions were mild to moderate and did not require infusion discontinuation. No infusion reactions occurred during the post-infusion observation. Patient experience was positive.Conclusion: Frequency or severity of infusion related reactions in rapid infusions were no different compared to published data. In the setting of COVID-19, pandemic rapid infusion protocols could potentially save hospital resources and limit patient exposure to a high-risk clinical setting while still maintaining ongoing treatment of multiple sclerosis.

Rapid Infliximab Infusion in the Pediatric Population.

To compare infusion reaction rates between rapid infliximab (REMICADE, Janssen Biotech Inc) infusions and previous standard 2- to 3-hour infusions; additionally, to assess patient satisfaction and reduction in chair time associated with rapid infliximab infusions. Pediatric rheumatology and gastroenterology patients receiving maintenance infliximab therapy using a standard 2- to 3-hour titrated infusion had the opportunity to enroll in the non-titrated rapid 1-hour infusion protocol following tolerance of induction dosing at 0, 2, and 6 weeks. Patients were included from December 1, 2017, to March 31, 2018, via retrospective chart review and patient satisfaction surveys. Data were collected on 55 patients receiving a total of 160 rapid infliximab infusions. There were 2 infusion reactions during the enrollment and data collection period, resulting in an overall infusion reaction rate of 1.3%. The patient satisfaction survey results showed all patients were at minimum satisfied with the information provided regarding rapid infliximab, decreased time spent in clinic, ease of scheduling, and overall process. Our data suggest rapid infliximab infusions are safe in pediatric rheumatology and gastroenterology patients receiving maintenance infliximab infusion therapy. The overall infusion reaction rate of 1.3% in this study is well below the accepted infusion reaction rate of standard-length infliximab infusions of 2% to 3%.

Safety of ninety-minute daratumumab infusion.

Daratumumab is the first anti-CD38 monoclonal antibody of the class approved for recurrent and refractory multiple myeloma. Grade 3 and 4 Infusion-Related Reactions (IRRs) are frequent during the first and second infusions. Due to the risks associated with severe IRRs, daratumumab is systematically administered over a period of 3.5 hours.The main objective of this study was to evaluate the safety of a 90-minute daratumumab infusion from the third infusion. All patients who had received two or more doses of daratumumab in monotherapy or in combination with standard infusion rates were included. We excluded patients enrolled in clinical trials. For the rapid infusion protocol, 20% of the dose was administered over 30 minutes and the remaining 80% over 60 minutes. From April 1 to May 31, 2019, 25 patients received 53 90-minute infusions of daratumumab. Premedication included corticosteroids, antipyretics, antihistamines, and if necessary a leukotriene receptor antagonist. No grade 3 or grade 4 IRRs were observed. From the third infusion, we found that a rapid administration of daratumumab (90 vs 210 minutes) was well tolerated and safe. It would be interesting to test this regimen from the second infusion.

Implementation and Evaluation of a 90-Minute Rituximab Infusion Protocol at the Richard L. Roudebush VA Medical Center

The use of IV rituximab for the treatment of a variety of malignant and nonmalignant indications has been associated with significant challenges related to time and labor. To help alleviate some of these logistic challenges, institutions have implemented protocols to shorten the time in which rituximab is infused. The purpose of this study was to support the safe implementation of a 90-minute rapid infusion protocol for rituximab at the Richard L. Roudebush VA Medical Center (RLRVAMC). A 90-minute rituximab protocol was developed, and proactive measures were taken to educate physicians, pharmacists, and nurses on ordering, processing, compounding, and administering rituximab. A weekly report of patients who received rituximab at RLRVAMC was generated November 1, 2018 through April 1, 2019. Patients then were screened for rapid infusion of the drug based on eligibility criteria, and health care providers (HCPs) were notified. After each patient received a rapid infusion, a retrospective chart review was performed to evaluate patient tolerability and assess for any safety concerns that would require protocol modification. The primary endpoint for this study was the incidence of grade 3 and 4 infusion-related reactions (IRRs) associated with rapid infusions of rituximab based on the Common Terminology Criteria for Adverse Events Version 5.0. Eleven patients received 24 rapid infusions of rituximab. Of these infusions, 1 (4.2%) resulted in a grade 3 IRR; no infusions resulted in a reaction of grade ≥ 4. The use of rapid infusion of rituximab when compared with nonrapid infusion saved 39.3 minutes on average per patient. The proactive measures that were used to implement the rapid infusion rituximab protocol improved HCP prescribing rates, nursing satisfaction, and the management of IRRs. This study confirmed appropriateness of rapid administration of rituximab in this veteran population and has increased interest in implementing other rapid infusion protocols.

Safety and Cost Benefits of the Rapid Daratumumab Infusion Protocol

IntroductionDaratumumab is approved for the treatment of multiple myeloma in both frontline and relapsed/refractory settings. Its major limitation is the long infusion time, especially with the first dose. Recent data demonstrated the feasibility of infusing daratumumab at an accelerated rate of 90 minutes starting from cycle 1 on day 15. Herein, we report the safety profile and cost associated with rapid daratumumab infusion protocol. Patients and MethodsA chart review was performed to identify patients who completed at least 1 cycle of daratumumab (single agent or in combination) from April 2016 to October 2018. Patients were divided into 2 cohorts: cohort 1 received rapid daratumumab infusion after its implementation in March 2018, whereas cohort 2 included patients treated with daratumumab administered at the standard rate. The primary endpoint was to compare differences in rates of infusion-related reactions (IRRs). An Excel (Microsoft)–based model was developed to estimate cost and productivity. ResultsA total of 100 patients with relapsed/refractory disease were included in this study (53 in cohort 1 and 47 in cohort 2). Of the 53 patients in cohort 1, 18 (34%) received rapid daratumumab infusion starting with cycle 1. Overall, there was no statistically significant difference in rates of IRRs between cohort 1 and 2 (1.9% vs. 4.3%, P = .59); 1 patient in cohort 1 developed an IRR. The total costs estimated for a 52-week regimen of daratumumab infused at standard and rapid rates were $137,200 and $122,200 (P < .001), respectively. ConclusionOur findings indicate that rapid daratumumab infusion is safe and tolerable and provides cost savings for patients with relapsed/refractory disease.

Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study

Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study

Rapid Infusion Daratumumab Is Safe in Patients with AL Amyloidosis

Introduction: Daratumumab (DARA) is an anti-CD38 human monoclonal antibody FDA-approved for the treatment of multiple myeloma (MM) and has demonstrated efficacy in AL amyloidosis. Infusion-related reactions (IRRs) occur in over 50% of patients treated with DARA, most commonly with the first infusion despite premedication with corticosteroids, antipyretics, antihistamines, and post-infusion corticosteroids. If DARA is tolerated without IRRs, the infusion rate can be escalated in standardized increments to a final infusion rate administered over 90 minutes in patients with MM (Barr et al. Leukemia 2018). Rapid infusions of DARA decrease length of infusion visits, potentially improving patient satisfaction and optimizing healthcare resources. Recent studies showed that DARA is safe and highly effective in treating AL amyloidosis (Khouri et al, Br J Haematol 2018), but no information is available regarding the safety of administering rapid infusions of DARA in patients with AL amyloidosis. We hypothesized that patients with AL amyloidosis, especially those with cardiac involvement, may not tolerate a rapid administration of fluids. Thus, a DARA rapid infusion protocol for patients with AL amyloidosis was implemented at our institution in April 2018. We report findings from the protocol implementation. Methods: A retrospective observational study was conducted to review adult patients with AL amyloidosis who received rapid infusions of DARA from April 2018 to October 2018. Data collected included relevant past medical history, vitals, premedications, infusion rates, and management of IRRs. Patients were eligible for rapid DARA after tolerating two prior doses of DARA at standard infusion rates. Rapid DARA was infused at 200 mL/hr for 30 minutes, then increased to 450 mL/hr for 60 minutes. Protocol premedications included acetaminophen, diphenhydramine, famotidine, and dexamethasone. No post-infusion corticosteroids were required. The first two standard and first four rapid DARA infusions were evaluated for each patient. Results: 27 patients with AL amyloidosis were included in the study with 162 doses of rapid DARA evaluated. Baseline characteristics included age (median 72 years old), gender (55.6% male), diastolic heart failure (59.3%), combined systolic and diastolic heart failures (11.1%), chronic obstructive pulmonary disease (7.4%), asthma (7.4%), and chronic kidney disease (25.9%). 62.9% of patients had cardiac AL involvement and 51.9% had renal AL involvement. 11/27 (40.7%) patients had IRRs to the first infusion of DARA (cycle 1, day 1) requiring hypersensitivity medications. All 27 patients progressed to rapid rate DARA after both initial and subsequent rates were tolerated. 22/27 (81.5%) patients initiated the first rapid DARA with the protocol premedications. Premedication usage decreased by the fourth rapid DARA dose with only 23.1% patients receiving diphenhydramine, 57.7% receiving famotidine, and 38.5% receiving dexamethasone (Figure 1). No patients received post-infusion corticosteroids. There were no clinically significant IRRs with the DARA rapid infusion protocol across all patients, regardless of organ involvement. There were 10 cases of CTCAE grade 2-3 hypertension that did not require intervention. No hypersensitivity medications were required for any rapid DARA doses. 11/11 (100%) patients who experienced IRRs requiring hypersensitivity medications during their first or second standard DARA infusions tolerated rapid DARA administration without recurrence of IRRs. Conclusions: Rapid administration of DARA is safe and well-tolerated in patients with AL amyloidosis, regardless of organ involvement. Patients who experienced an IRR with the initial DARA dose were able to safely transition to the rapid infusion protocol without recurrence of IRRs. Furthermore, decreased premedication usage after tolerance of rapid DARA infusion did not increase IRRs, suggesting premedications can be discontinued to mitigate associated toxicities. Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau. Valent:Celgene corporation: Speakers Bureau; Amgen corporation: Speakers Bureau; Takeda pharmaceuticals: Speakers Bureau. OffLabel Disclosure: Daratumumab for the treatment of AL amyloidosis

Prevention and Management of Daratumumab Mediated Infusion Related Hypersensitivity Reactions Pre-and Post-Implementation of Rapid Infusion Protocol

Background: Multiple Myeloma (MM) is defined as a clonal proliferation of malignant bone marrow plasma cells with high and uniform expression of CD 38 (Kumar et al, J Natl Compr Canc Netw. 2019; 3 and Lin et al, Am J Clin Pathol. 2004; 121:482-488). Daratumumab, a human IgGk monoclonal antibody, targets and binds to CD38, induces antibody dependent cell mediated cytotoxicity, complement activation, and antibody mediated phagocytosis (Prescribing information. Daratumumab; Janssen Biotech, Inc 2016). Daratumumab is associated with infusion related reactions (IRRs), which present with symptoms of rhinitis, cough, dyspnea, bronchospasm, chills and nausea. In two phase 3 trials, CASTOR (Palumbo et al, N Engl J Med. 2016; 375:754-66) and POLLUX (Dimopolous et al, N Engl J Med. 2016; 375(14):1319-31), IRRs occurred in 45% and 48% of patients, respectively. Of these, 98% and 96%, respectively, occurred during the first infusion. Grade 3 IRRs occurred in 5.3% and 8.6% of patients in CASTOR and POLLUX, respectively. No grade 4 IRRs were observed in either trial. Standard of care includes extended infusion times for the first, second, and subsequent infusions with a three-drug pre-infusion prophylaxis strategy including diphenhydramine, dexamethasone or methylprednisolone, and acetaminophen with slow prolonged infusion times is recommended(Bhatnagar et al, Oncologist. 2017; 22:1347-53). A single-arm safety study of accelerated infusion rate indicate that administering daratumumab using a time-saving 90-minute infusion protocol can be safe. Of 28 patients treated with accelerated daratumumab infusion during their third and subsequent infusions, no IRRs were observed, and there was only one mild reaction with no further reactions during subsequent infusions at the 90-minute rate (Barr et al, Leukemia. Mar. 2018). Subsequently, a similar protocol for all daratumumab infusions was implemented at The Johns Hopkins Health System including five premedications and three medications (5+3) during the first two infusions. Premedication can be eliminated for lack of tolerance. The purpose of this study is to evaluate the safety and success of rapid daratumumab administration in clinical practice based on infusion times, IRRs prophylaxis medication administration, IRRs frequency, and management of IRRs in the ambulatory setting of the Johns Hopkins Health System, pre- and post-implementation of the 90-minute infusion protocol using a more robust premedication regimen (5+3) than previously published. Study Design and Methods: This study is approved by the institutional review board at The Johns Hopkins Hospital (IRB 00195519). This is a retrospective, chart review of daratumumab infusions prior to implementing the accelerated infusion rate. The inclusion criterion was adult patients who received daratumumab infusion in the ambulatory infusion clinic July 1, 2016 to May 25, 2018 for pre-implementation and July 1 2018 to June 30 2019 for the post-implementation period. Patients who only received inpatient administration of daratumumab were excluded due to limited infusion related documentation. The primary endpoint is the proportion of patients who experienced IRRs after daratumumab infusion. Secondary endpoints include proportion of patients with grade 1/2 or grade 3/4 IRRs, infusion duration (hours), and the number of pre and post infusion prophylaxis medications given. Other data collected will include but not limited to demographics, prior history of anaphylaxis, eczema, asthma, or other drug allergies to identify risk factors not previously defined. Results: Data collection and analysis are ongoing. The sample size for pre-implementation of rapid infusion is ninety-three patients. Documented IRRs occurred in 18 (19%) patients. The mean infusion time was 7.4 hours for first infusions (n=70), 8 hours for patients with IRRs in the first infusion (n=18) and 7.1 hours for patients without IRRs in the first infusion (n=52). The mean number of IRR prophylaxis medications given was 7.8 (range 2-9) for first or second infusions. All IRRs documented were grade 1 or 2. Additional data analysis will include descriptive statistics as well as comparison of infusion duration, and will use paired t-test within samples and student t-test across different samples. Final results will report safety of daratumumab rapid infusion in largest single center patient population to date. Disclosures Ali: Celgene: Research Funding; Poseida: Research Funding.

PS1300 A NURSE LED IRON INFUSION CLINIC REDUCES POTENTIAL PATIENT HARM AND IMPROVES HOSPITAL EFFICIENCY

Background:The introduction of a rapid iron infusion protocol (ferric carboxymaltose) whilst more convenient and safe for patients has the potential to change the management of iron deficiency anaemia (IDA) away from best practice guidelines. Latrobe Regional Hospital (LRH) deliver all outpatient intravenous (IV) iron infusions through their chemotherapy day unit (CDU), providing an opportunity to study the total prescribing practices in a busy rural referral centre.Aims:To assess the appropriateness of intravenous iron prescribing in a regional setting and implement service improvement projects where deviations from best practice were identified.Methods:Baseline data of all IV iron infusions was collected from May 2017 to January 2018 (PRE phase 9 months). From February to October 2018 (POST‐phase 9 months), referrals from primary care physicians requesting an iron infusion were assessed by a haematology clinical nurse consultant (CNC) iron infusion clinic with physician supervision. All internal medicine specialist requests for iron infusions were coordinated by the haematology CNC. Iron infusion and prescribing rates were summarised for three groups, physician, local medical officer (LMO) and obstetrics and gynaecology (O &amp; G). All requests for iron infusions were assessed according to best practice guidelines.Results:Table one summarises the total 311 iron infusions delivered over the 9‐month pre‐phase data collection period. The physician group referred an older population of both males and females. The LMO referral group were predominantly female.Figure one shows the average monthly IV iron infusions delivered for the entire collection period and as per each referral group.There was a significant reduction in the average monthly IV iron infusions from 38 to 23. Monthly infusions delivered following referrals from the LMO group reduced significantly from 17 to 6. Whilst referrals from the physician group increased and O &amp; G group decreased, these were not significant.Summary/Conclusion:The development of an iron infusion clinic led by a haematology CNC provides a safe evidenced based assessment of patient referrals. This model significantly reduced the rate of iron infusions in our regional hospital, allowing more efficient use of the expert outpatient infusion centre services and reducing potential harm related to an inappropriate therapy.image

Decreasing Door-to-Door Times for Infliximab Infusions in a Children's Hospital Observation Unit.

Children with inflammatory bowel disease (IBD) often require infliximab infusions to manage their disease. Infusions administered in the hospital setting require the patient and their families to devote many hours away from home. Changing to a rapid infusion protocol has been shown in the literature to be safe and has the potential to decrease time spent in the hospital receiving infusions. We describe stepwise changes made over a 4-month period to improve infliximab infusion efficiency and lessen the time spent in the hospital by IBD patients and their families. These changes included the implementation of a standardized order set, defaulting to rapid infusions for eligible patients, eliminating the post-infusion observation window, and improving the pharmacy's efficiency in preparing infusion medications. We utilized several established quality improvement tools, including a smart aim, key driver diagram, plan-do-study-act cycles, and statistical process control charts to measure these interventions. Within three months of starting, the average door-to-door time patients spent in the hospital decreased by 128 minutes (2 hours 8 minutes). This improvement amounts to 768 minutes (12 hours 48 minutes) per year of time returned for normal childhood activities outside of the hospital. There were no infusion reactions during the period monitored. Implementation of a rapid infliximab infusion protocol made an impressive impact on freed family time without sacrificing patient safety. The changes we implemented could be helpful to other centers interested in decreasing in-hospital time for patients with IBD and their families.

Rapid Infusion Daratumumab Is Safe and Well Tolerated in Clinical Practice

Introduction: Daratumumab is an anti-CD38 monoclonal antibody, currently FDA approved for treatment of newly diagnosed transplant ineligible multiple myeloma (MM) in combination with melphalan, prednisone and bortezomib, in combination with lenalidomide-dexamethasone and bortezomib-dexamethasone for early relapse MM, and in combination with pomalidomide-dexamethasone and monotherapy for relapsed/refractory MM (RRMM). Recent data demonstrated the feasibility of infusing daratumumab at an accelerated rate over 90 minutes from Cycle1 day 15 onwards [1], reducing the standard infusion time of 3-4 hours. Considering these data, all daratumumab protocols at our institution were updated to implement the rapid infusion protocol in routine clinical practice. Herein, we report the safety profile of rapid daratumumab infusion at our center.Methods: Retrospective chart review was performed from April 2016 through July 2018 to identify patients who completed at least one cycle of daratumumab or any daratumumab containing regimen for RRMM or amyloidosis at the Levine Cancer Institute (LCI). LCI includes a large infusion center at the main tertiary center and several other small infusion centers distributed throughout the states of North and South Carolina. Patients were divided into two cohorts; cohort 1 included patients who received daratumumab administered at the standard infusion rate recommended by manufacturer, whereas cohort 2 received rapid infusion daratumumab following the institution-wide implementation of the rapid infusion protocol in March 2018. Cohort 2 patients started on daratumumab received the first two doses of cycle 1 at the standard infusion rate followed by a 90-minute infusion with third and subsequent doses. Furthermore, 20% of dose was given over 30 minutes and the remaining 80% over 60 minutes (overall duration: 90 minutes). Patients in both cohorts were pre-medicated with: acetaminophen, diphenhydramine, dexamethasone and montelukast (for first two doses of first cycle), given 30 minutes prior to initiating daratumumab. The primary endpoint was to compare rates of infusion related reactions between the rapid and standard daratumumab infusion protocols using Fischer's exact test. Data collected included but not limited to: patient demographics, comorbidities, plasma cell disorder, pre-medications, type and management of infusion reactions, as well as post-infusion monitoring if documented.Results: A total of 73 RRMM (37 in cohort 1 and 36 in cohort 2) and 6 amyloidosis patients (3 in each cohort) were included in this study. Baseline characteristics are shown in table 1. Overall, there was no statistically significant difference in the rates of infusion related reactions between the rapid and standard infusion cohorts (2.6% vs. 5.0%, p=0.6). Of 39 patients in cohort 2, 8 patients received rapid infusion daratumumab on day 15 (3rd dose) of first cycle, whereas remaining received a median of 7 cycles (range: 2-30) before the switch was commenced. Among those 8 patients where daratumumab was started on day 15, only 1 developed an infusion related reaction. Notably, this patient had a history of prior exposure, and subsequently daratumumab was administered at the rapid infusion rate on day 1 instead of day 15, approximately 4 months later. All infusion reactions reported in both cohorts were grade 1 which were managed according to institutional guidelines followed by resumption of infusion at lower rates.Conclusion and future directions: Our findings indicate that rapid daratumumab infusion beyond day 8 of cycle 1 is a safe, tolerable and convenient option for RRMM and amyloidosis patients. Additional studies are underway to evaluate cost benefits of rapid infusion daratumumab as well as patient/provider satisfaction.

Successful Transition to an Infliximab Biosimilar at an Academic Hospital

Introduction: Health systems face pressure from payors (government subsidized and commercial) to reduce medical expenses. The biosimilar infliximab-dyyb (IFX-dyyb, Inflectra) presents an opportunity to bend the cost curve, with a savings of 20-30% over infliximab (IFX, Remicade). In addition, organizations such as the Crohn's and Colitis Foundation are not opposed to a one-time switch between an originator and biosimilar by third parties (www.crohnscolitisfoundation.org/resources/biosimilars.html). However, many institutions struggle to operationalize biosimilar adaptation due to a lack of consensus amongst providers, lack of interchangeability designation from the FDA, and payor incentivization on the back end with significant rebates. Methods: After a review of clinical data, discussions with all prescribing providers and formulary committee approval, Boston Medical Center (BMC) decided to replace IFX with IFX-dyyb as the preferred formulary agent for all indications. Patients who had been on IFX for at least 6 months or who were new starts to IFX after 3/5/18 were identified to recieve IFX-dyyb. Those patients who received IFX via home infusion or in multiple locations were excluded. The BMC rapid infusion protocol remained unchanged for those patients transitioning to IFX-dyyb. Results: By end of May 2018, 124 patients were identified to receive IFX-dyyb. Patients receving infusions at home (n=1) or in multiple locations (n=4) were excluded. Payors, primarily Harvard Pilgrim Health Care, denied IFX-dyyb for 13 patients as it was not deemed medically necessary. Only 3 patients declined the switch to IFX-dyyb, but 1 was later excluded due to change in infusion location. A total of 108 patients are now receiving IFX-dyyb (8 new starts and 100 transitions). This represents a conversion rate of 98% (108/110 patients) excluding payor denials. Pharmacists spent an average of 5-10 minutes on the phone per patient providing education and answering questions. Conclusion: The transition from IFX to IFX-dyyb represents a reduction in health care costs to BMC. However, it is important to note that contracts between payors and pharmaceutical companies working against the biosimilar adoption leave health systems with the cost. Operationally, we felt that the educational telephone outreach to patients helped facilitate the adaptation of the biosimilar IFX-dyyb at our institution. The high patient conversion rate achieved at BMC shows that transition to a biosimilar is feasible with a team approach.1141 Figure 1. Flow chart detailing patient selection and tasks undertaken by the pharmacy team to inform patients of the switch to IFX-dyyb.