Rate Of Infusion Reactions Research Articles

P1306 Impact of HLA-DQA1*05 genotype in immunogenicity and response to treatment with Tumour Necrosis Factor-alpha Antagonists in Inflammatory Bowel Disease patients

Abstract Background Carrying the HLA-DQA1*05 gene has been linked to a higher risk of developing immunogenicity in patients with inflammatory bowel disease (IBD) who are treated with tumor necrosis factor-alpha (TNF-a) inhibitors. However, studies have shown inconsistent evidence regarding its connection to a loss of response or adverse events in patients with IBD. The aim is to determine the impact of carriage of HLA-DQA1*05 allele on effectiveness, drug persistence and safety in patients diagnosed with IBD who had received antiTNF-a inhibitors. Methods Retrospective, single-center cohort study including IBD patients who had received anti-TNF therapy. The HLA-DQA1*05 allele was determined retrospectively from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits. We evaluate drug persistence, withdrawal of antiTNF-a, clinical response/remission, primary and secondary loss of response, through antiTNF levels, development of antiTNF antibodies and adverse events in patients distributed by HLA-DQA1*05 allele presence. Results A total of 82 patients were included. Baseline characteristics are detailed in Table 1. HLA-DQA1*05 was positive in 35/82 (42.7%) patients. Sixty-three patients (63%) received infliximab (IFX) and 19/82(23.2%) adalimumab. AntiTNF was the first advanced therapy in 78/82(95%) of the cohort. Thirty-four out of 82 patients (41%) received an optimized antiTFN-a regimen, as well as 34/82 (41%) were treated with combo-therapy with immunosuppressants. AntiTNF-a was withdrawn in 35/82 (42.7%) patients during follow-up, and the rate of adverse events that led to discontinuation of the drug was 16% (13/82). When we compared the rate of primary and secondary non-response, persistence of the antiTNF-a therapy or use of combo-therapy, we did not find significant differences between patients by HLA-DQA1*05 status. On the other hand, the rate of infusion reactions, development of anti-TNF antibodies or adverse events that led to drug withdrawal were also similar among patients HLA-DQA1*05 positive or negative. Only the need of optimized antiTNF-a was more frequent among patients HLA-DQA1*05 positive (19(54.3%) vs. 15 (31.9%), p= 0.028). Conclusion In our real-life cohort of IBD patients treated with antiTNF-a, being an HLA-DQA1*05 carrier did not act as a predictor of loss of response, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant. However patients HLA-DQA1*05 positive required optimized antiTNF-a regimen more frequently.

Horse antithymocyte globulin test doses and infusion reactions in adults with aplastic anemia: A multicenter retrospective experience

Introduction Horse antithymocyte globulin carries a black box warning for life-threatening anaphylactic reactions, and prescribing information recommends test doses to identify patients at highest risk of this adverse effect. The predictive value of such test doses is not well validated, and practicality of use is unclear. Methods This was a planned secondary analysis of a multicenter, retrospective cohort study in adults with severe aplastic anemia being managed with horse antithymocyte globulin as part of their treatment regimen. Qualitative and quantitative descriptions of test doses and infusion reactions are summarized, alongside key institutional administration practices. Results Of 49 patients who received intradermal test doses, two experienced positive reactions and went onto receive their full horse antithymocyte globulin course through prolonged infusion time or desensitization. Infusion reaction rate in patients with negative test doses was 61%, corresponding to a negative predictive value of 39%. Premedication, infusion time, and infusion reaction management were similar across institutions. Conclusion Horse antithymocyte globulin has a high risk of infusion reactions that must be monitored and managed closely. However, test doses do not consistently predict who will experience an infusion reaction, and their practicality may be limited with current administration practices.

Rituximab-associated adverse events in nephrotic syndrome: A systematic review and meta-analysis.

Rituximab (RTX) has been recommended to treat nephrotic syndrome (NS), but its safety has not been quantitatively analyzed. PubMed, Embase, and the Cochrane Register of Controlled Trials databases were searched from inception to December 31, 2023, for randomized control trials (RCTs) and retrospective studies reporting the adverse events (AEs) related to RTX for treating NS. Data were expressed as odds ratios (OR) and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was identified using the Cochrane Q test and quantified by the I 2 statistic. Ten RCTs and five retrospective studies with 1231 patients were enrolled. RTX significantly reduced the risk of total AEs (OR=0.32, 95% CI [0.13, 0.78]) compared to the non-RTX group in retrospective studies but was not in RCTs. The pooled rate of infusion reactions was 32% (95% CI=[19%, 45%]) in RCTs and 8% (95% CI=[3%, 13%]) in retrospective studies. Subgroup analyses demonstrated a lower risk of hematological events in adult NS patients (OR=0.21, 95% CI [0.09, 0.51]) and the 1000mg RTX intervention (OR=0.21, 95% CI [0.09, 0.51]). There is no significant difference in serious AEs, infection, gastrointestinal, renal, cardiovascular, and cancer events between the two groups. RTX reveals great potential in terms of safety compared to non-RTX treatments due to the relatively few AEs in our results. However, the interaction of other drugs needs to be monitored. The safety of RTX in NS patients needs to be further confirmed in high-quality clinical trials.

Real-World Comparative Analysis of Trastuzumab Originator and Biosimilars: Safety, Efficacy, and Cost Effectiveness.

Despite the global use of trastuzumab biosimilars, concerns remain regarding their efficacy and safety. In particular, when used concurrently with pertuzumab, trastuzumab biosimilars lack extensive real-world data and safety information. Additionally, as cancer drug expenditures continue to rise worldwide, cost savings from biosimilars have become increasingly important. This study aims to assess the safety, efficacy, and cost effectiveness of trastuzumab originators and their biosimilars in real-world clinical settings, focusing on a large patient population. The analysis included 31,661 patients with HER2-positive breast cancer from the Medical Data Vision Co., Ltd. database in Japan. Additionally, adverse event reports for the trastuzumab originator and its biosimilars were obtained for 58,799 patients from the World Health Organization's VigiBase, the global adverse event reporting database. No significant differences were observed in heart failure hospitalizations, liver dysfunction, or infusion reaction rates in both the Medical Data Vision Co., Ltd. database and the World Health Organization's VigiBase. In the Medical Data Vision Co., Ltd. database, the addition of pertuzumab did not significantly influence the incidence of adverse events, and the use of biosimilars significantly reduced medical costs, with no significant difference in breast cancer recurrence rates. By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice.

CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Systemic Autoimmune Diseases.

A small number of drugs have been the sole stay of conventional treatment for autoimmune illnesses for the past 10 years. These medications have a number of side effects that restrict their usage and necessitate continuous administration to keep a patient in a state of remission. While many new treatments are being researched to address this problem, chimeric antigen receptor (CAR) T-cell therapy currently shows the greatest potential. Current medical guidelines do not currently advocate the use of this medicine because it is still in its early stages of development due to continuing clinical research. Therefore, the aim of this systematic review was to determine what new findings have been reported in recent studies about the safety and efficacy of CAR T-cells. From the nine studies collected in total, it was found that systemic lupus erythematosus (SLE) was the most often researched autoimmune disease. The CAR T-cell therapy had noticeable results after one to two months on average. The most frequent adverse effect was cytokine release syndrome (CRS), which was treated cautiously and infrequently necessitated extensive intervention. All serological tests showed improvement, and clinical remission was always achieved. This review concludes that, due to the one-time infusion and low adverse reaction rate, the therapy not only outperforms conventional drugs but is also more practical. There is even more cause to look forward to the full deployment of this innovative therapeutic alternative, as variations of the therapy are currently being explored.

Use of daratumumab drug formulation for subcutaneous administration in multiple myeloma therapy: Literature review and clinical observation

Study of the molecular pathogenesis of multiple myeloma led to development and introduction of antitumor agents with new mechanisms of action and their combinations into clinical practice. According to several trials, use of anti-CD38 monoclonal antibody daratumumab as part of triplet therapies at an early stage leads to deep and long-term antitumor response, achievement of MRD-negative status, and, as a result, increased survival and improved prognosis in all patient subgroups. High effectiveness of daratumumab subcutaneous formulation close to intravenous formulation has favorable safety profile, short administration time and low rate of infusion reactions which improves patients’ quality of life, affects their treatment compliance, and decreases healthcare costs.We present a clinical observation of a 60-year-old patient with newly diagnosed multiple myeloma who previously underwent treatment for another lymphoproliferative disorder which included autologous hematopoietic stem cell transplantation leading to complete and long-term remission. After 9 intravenous daratumumab infusions (with recommended dose of 16 mg/kg) in accordance to the D-Rd regimen, evaluation of antitumor effect and consideration of socially active lifestyle of the patient, daratumumab formulation for intravenous administration was replaced with subcutaneous formulation of fixed dose 1800 mg. Further deepening of the antitumor response was observed along with manageable safety profile and absence of significant adverse events which allowed to maintain intercourse intervals and improve the patient’s quality of life.

Infusion Reactions with Alternative Therapies during the National Shortage of Iron Dextran

Introduction The national shortage of intravenous iron dextran has required patients to receive more alternative iron infusions, such as iron sucrose and sodium ferric gluconate/sucrose, since January 2023. While prior studies have evaluated rates of infusion reactions among some commonly used intravenous iron formulations, data is lacking among differing doses of iron formulations and especially in the setting of this iron dextran shortage. Clinicians at our institution generally observed more adverse reactions with alternative iron infusions during the national shortage of iron dextran compared to prior. Our study examines the infusion reactions of various iron therapies at differing doses and actions providers and patients took thereafter to assess the impact of the iron dextran national shortage on patients. Methods Patients were included who received iron infusions in three Henry Ford Hospital clinics in metropolitan Detroit, Michigan, from July 2022-June 2023 with the national iron dextran shortage impacting the health system since January 2023. Age, race, sex, reason for iron infusion, iron infusion formulation received, time of infusion, and dosing schedule of infusion were recorded for all participants. We assessed the symptoms experienced and actions taken for patients who had an infusion reaction. The number and type of infusion reactions between different iron infusion formulations and doses were then compared. Results Of the 880 unique patients assessed, 496 (56.4%) received iron dextran, iron sucrose, or sodium ferric gluconate/sucrose between July 2022 and December 2022 prior to the national iron dextran shortage and 384 (43.6%) patients had iron infusions between January 2023 and June 2023 during the shortage. Iron dextran accounted for most of the infusions (n= 356, 71.8%) prior to the shortage whereas iron sucrose was the majority (n=312, 81.3%) during the shortage. Prior to the national shortage, 30 iron infusions reactions occurred, with 18 (60%) associated with iron dextran, 9 (30%) with iron sucrose, and 3 (16.7%) with sodium ferric gluconate/sucrose. During the shortage, 44 reactions occurred, with 1 (2.27%) associated with iron dextran, 41 (93.1%) with iron sucrose, and 2 (4.54%) with sodium ferric gluconate/sucrose. The most reactions (n=41, 55.4%) occurred with iron sucrose at a dose of 500mg across the whole study period. Less reactions (n=9, 12.2%) were reported for iron sucrose at progressively lower doses, comparable to reactions with iron dextran at doses greater than 1000mg (n=8, 10.8%) and at lower doses of iron dextran (n=10, 13.5%). The most common reaction across all infusion types was nausea, vomiting, and/or diarrhea. After an iron infusion reaction, the infusion plan was then most commonly discontinued, with patients either switching to alternative iron infusion formulations, continuing the same infusion type with medications for symptoms, or continuing the same infusion type with lower dose and increased frequency. Conclusion More iron infusion reactions occurred after the national shortage of iron dextran since January 2023 in the setting of more frequent use of alternative iron therapies. The most common infusion formulation associated with a reaction was iron sucrose at its higher recommended dose of 500mg, compared with iron dextran and sodium ferric gluconate/sucrose. Providers should be aware of these associated adverse reactions with the different doses of alternative formulations when recommending infusions for patients, and the need for preemptive intervention.

Multidisciplinary Approach to Deciphering Etoposide Infusion Reactions and Potential Role of Polyethersulfone Filter Membranes.

Etoposide, a topoisomerase II inhibitor used clinically to treat cancer, has been associated with severe anaphylactic infusion related adverse drug reactions (ADRs). In a previous study we identified a hydrophilic polyethersulfone filter as a possible cause of increased rates of pediatric etoposide infusion reactions. In this multidisciplinary follow-up analytical study, we aimed to assess the chemical structure of etoposide after passing through the same hydrophilic polyethersulfone filter. An etoposide 0.4 mg/mL infusion was prepared under aseptic conditions and then passed through a standard IV infusion set with an in-line filter in place. Samples were taken in triplicate using a needle-less access system to include sampling sites directly from the IV bag port and from the IV tubing both before and after the in-line filter. Samples were diluted into mobile phase, then an aliquot was injected into a high-performance liquid chromatography mass spectrometry HPLC-MS (Thermo TSQ Quantum Ultra) system coupled to a Diode Array Detector (DAD) (Thermo Dionex Ultimate 3000). Etoposide was monitored using a selected reaction monitoring scan (SRM) of 606.2/228.8 and wavelengths of 210, 220, 254, and 280 nm for 30 minutes. No detectable differences were observed upon comparing the three samples. Based on these results, a chemical change in etoposide resulting from an in-line filter is unlikely to be the primary cause of increased rates of infusion reactions. Pharmacists working in healthcare systems, observe many ADRs, but rarely have the resources necessary to investigate the potential etiology or causality. This report highlights importance of multi-disciplinary collaboration to investigate serious ADRs.

HLA-DQA1*05 Was Not Associated With Primary Nonresponse or Loss of Response to First Anti-TNF in Real-World Inflammatory Bowel Disease Patients.

We lack predictors of response to biologics in the management of patients with inflammatory bowel disease (IBD). A recent study has shown a significant association between HLA-DQA1*05 carriers and the development of loss of response to anti-tumor necrosis factor (TNF) mediated by immunogenicity. Retrospective single-center cohort study including IBD patients who had received anti-TNF therapy as a first biologic and whose HLA-DQA1*05 had been determined. Primary nonresponse and secondary failure (assessed by survival analysis) have been evaluated as well as safety outcomes. A total of 199 IBD patients (161 [81%] with Crohn's disease and 38 [19%] with ulcerative colitis) were included. A total of 42.4% were HLA-DQA1*05 carriers and 60% received combination therapy at the start of anti-TNF treatment. Median follow-up was 24 (interquartile range, 11-66) months. No statistically significant differences were found in primary nonresponse to anti-TNF (89.3% vs 87.8%; P = .825), depending on HLA carriers and noncarriers. No differences in secondary loss of response according to HLA variant in any of the analyses performed (full cohort, according to IBD or anti-TNF type) were observed. Again, no differences were observed in patients treated with combination therapy. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events. In our real-life cohort of IBD patients treated for the first time with anti-TNF, being an HLA-DQA1*05 carrier did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the variant.

Accelerated Infliximab Infusion Safety and Tolerability Is Non-inferior to Standard Infusion Protocol in Inflammatory Bowel Disease Patients: A Randomized Controlled Study.

Infliximab is typically given over an infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared with the standard 2-hour infusion. Open-label randomized trial where IBD patients receiving maintenance infliximab infusions were randomly assigned to 1- and 2-hour infusion groups, corresponding to study and control groups, respectively. The primary outcome was the rate of infusion reactions. Secondary outcomes were assessment of the effect of premedications and immunomodulators on the rate of infusion reactions, and cost-effectiveness analysis. The cost-effectiveness analysis was based on direct nursing costs for the infusion time, indirect infusion center costs, and cost of productivity loss for patients. This trial is registered with ClinicalTrials.gov, NCT05340764. From November 2020 to November 2021, 96 patients were randomly assigned: 51 (53%) to the 1-hour infusion group and 45 (47%) to the 2-hour infusion group. Over a median time of 1 year, 309 infusions were administered in the control group, and 376 in the study group. Fifty-seven (18%) infusions in the control group and 45 (12%) infusions in the study group experienced an infusion reaction. The only infusion reaction was asymptomatic hypotension not requiring infusion discontinuation. No other infusion reactions (mild or moderate/severe) were seen. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18-3.52], P = .01). The average costs were estimated to reduce by 37% in the accelerated infusion group. Accelerated 1-hour infusions are non-inferior in safety and superior in cost-effectiveness compared with standard 2-hour infusions in IBD patients receiving maintenance infliximab infusions. Registered with ClinicalTrials.gov, NCT05340764.

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.

P627 HLA DQA1*05 was not associated to primary non-response or loss of response to first anti-TNF in real world Inflammatory Bowel Disease patients.

Abstract Background Biologics have been a breakthrough in the management of patients with inflammatory bowel disease (IBD). However, we lack predictors of response to these drugs. A recent study has shown a significant association between HLA DQA*105 mutations and the development of loss of response to anti-TNF mediated by immunogenicity. The high quality of the study and the wide differences found, have led to its quick practical implementation in the choice of biological agent. However, the supporting evidence is limited in clinical practice. Methods Retrospective cohort study, carried out at the Miguel Servet Hospital, Zaragoza, Spain. We included IBD patients who had received anti-TNF therapy as first biologic and whose HLA DQA1*05 had been determined. Primary non-response and secondary failure (assessed by survival analysis) has been evaluated as well as safety outcomes. Results 199 IBD patients [161 (81%) Crohn′s disease (CD) 38 (19%) ulcerative colitis (UC)] were included. 42.4% had HLA DQA1*05 mutation and 60% received combination therapy with immunomodulators at the start of anti-TNF treatment. Median follow-up was 24 months (IQR 11-66). No statistically significant differences were found in primary non-response to anti-TNF (87,8% vs 12,2%, p = 0,825), depending on the presence or absence of HLA mutation. No differences in secondary loss of response according to HLA mutation in any of the analyses performed (full cohort, according to IBD or anti TNF type) were observed (Figure 1). Secondary loss of response has also been assessed according to the use or non-use of concomitant immunomodulator. Again, no differences were observed in this analysis (Figure 2). Multivariate analysis, like the univariate analyses, showed that the presence of the HLA-DQA1*05 mutation was not associated with a higher rate of secondary loss of response or shorter time to failure. In terms of safety, no significant differences were found in the rate of infusion reactions or serious adverse events between carrier and non-carrier patients. Conclusion In our real-life cohort of IBD patients treated for the first time with anti-TNF, the presence of the HLA-DQA1*05 mutation did not act as a predictor of response failure, either primary or secondary. The safety of anti-TNF treatment has also not been influenced by the mutation. More data is needed to incorporate HLA DQA1*05 determination into routine clinical practice as a key factor in individual decision making.

ACCELERATED INFLIXIMAB INFUSION SAFETY AND TOLERABILITY IS NON-INFERIOR TO STANDARD INFUSION PROTOCOL IN INFLAMMATORY BOWEL DISEASE PATIENTS – A RANDOMIZED CONTROLLED STUDY

Abstract BACKGROUND & AIM Infliximab is typically given over a standard infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. Several retrospective and prospective studies have assessed the safety of accelerated infliximab infusions, but not in a randomized controlled setting. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared to the standard 2 hour infusion. METHODS This open label randomized trial was done at a tertiary IBD center in the United States. Patients with an established diagnosis of IBD receiving maintenance infliximab infusions at one of our centers were eligible for inclusion. We excluded patients with a history of infusion reactions and those with known antidrug antibodies to infliximab. Patients were randomly assigned (1:1) to the 1 hour infusion (study) and 2 hour infusion (control) groups using an independent computerized randomization system. The primary outcome was to assess the rate of infusion reactions in the standard 2 hour compared to the accelerated 1 hour study groups. Secondary outcomes were assessment of the effect of pre-medications and concomitant immunomodulators on the rate of infusion reactions, and cost effectiveness analysis. Sample size calculation was based on an infusion reaction rate of 3%, as suggested by recent studies. In order to show a non-inferiority of the accelerated infusion time assuming an infusion reaction rate of 3% while allowing for a 4% non-inferiority limit, a total of 538 infusions would be needed. This would provide a power of 80% and significant alpha of 0.05. Non-inferiority was assessed using Farrington-Manning score test. This trial is registered with ClinicalTrials.gov, NCT05340764. RESULTS From November 2020 to November 2021, we assessed the eligibility of 448 patients, of whom 352 (78%) were excluded primarily due to infusions being received at an outside institution, or patient refusal. Thus, 96 (22%) patients were randomly assigned: 51 (53%) to the 1 hour infusion study group and 45 (47%) to the 2 hour infusion control group. Over a median time of 1 year, a total of 685 infusions were administered: 309 infusions in the control group, and 376 in the study group. 57 (18%) of 309 infusions in the control group and 45 (12%) of 376 infusions in the study group experienced an infusion reaction. The only infusion reaction experienced was hypotension, all of which were asymptomatic and none required infusion discontinuation. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18 – 3.52], p=0.01). Average costs were estimated to reduce by 37% in the accelerated infusion group. CONCLUSION Accelerated 1 hour infliximab infusions are non-inferior in safety and superior in cost-effectiveness compared to standard 2 hour infusions in IBD patients.

1144. Rate of Infusion Reactions Among Patients Receiving Casirivimab/Imdevimab in the Home Setting

Abstract Background Monoclonal antibodies used in the treatment and prevention of COVID 19 infection are an emerging area of infectious disease. Casirivimab/imdevimab received emergency use authorization (EUA) for the prophylaxis and treatment of COVID 19 disease. Infusion reactions may occur with the administration of monoclonal antibodies and can be relieved by slowing or stopping the infusion rate. During the casirivimab/imdevimab EUA, the National Home Infusion Foundation (NHIF) collected data to determine patient outcomes and the incidence of infusion reactions. Infusion rate and premedication protocols were also studied. Methods Home infusion companies nationwide were invited to participate in this study by completing a short survey to determine eligibility. The data variables investigated included infusion time, adverse events, and whether standard orders for premedications were used. The data was collected using an Excel® spreadsheet and a follow-up survey verified the relationship between the length of infusion and ADR incidence. The data was imported to IBM SPSS® (Statistical Product and Service Solutions®) for additional analysis. Results With this patient sample, the infusion time was either 20, 30, or 50 minutes with most (62.60%) being 20 minutes (Exhibit: Infusion Time). Infusion rates were based on organization protocols, standard prescriber orders, or the clinical needs of the patient. Of the 464 patient cases, 95.26% (n=442) had no reported adverse event. Of the 22 cases with a reported event, the most common symptoms were fever (6) and hypotension (4). Premedications were not routinely included in standard prescribing orders and were based on patient specific situations. Conclusion Administration of casirivmab/imdevimab in the home setting showed a low incidence of adverse drug reactions, and the incidence of infusion reactions were not directly related to infusion time or premedication use. Disclosures All Authors: No reported disclosures.

Efficacy of Short-Duration Alemtuzumab in T-Cell Large Granular Lymphocytic Leukemia: Potential for a Response-Adapted Strategy

Introduction T-cell large granular lymphocytic leukemia (T-LGL) is a chronic incurable malignancy where once refractory to immunosuppressive therapy, few treatment options and no optimal treatment consensus exists. Alemtuzumab, 10 milligrams (mg) intravenously (IV) administered daily for a total of 10 doses, has been shown to be effective for relapsed or refractory (R/R) T-LGL (Dumitriu, et al. Lancet Haematol 2016); however, it can be associated with severe infusion reactions and infections. Given the palliative nature of T-LGL-directed treatments and the increasing potential for toxicity with cumulative alemtuzumab exposure, we conducted a retrospective analysis to describe the efficacy and safety of abbreviated alemtuzumab regimens in R/R T-LGL patients. Methods We identified patients ≥18 years with R/R T-LGL who were treated with short-duration (defined as ≤ 5 doses) alemtuzumab between 2012 and 2022 from the University of Washington lymphoma database. Patients who received prior alemtuzumab were excluded. The primary endpoint was overall hematologic response rate (ORR). Secondary efficacy endpoints included hematologic response rate at 3 and 6 months, rate of transfusion independence, progression-free and overall survival. Safety endpoints included rate of infusion reactions and infections, specifically Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation. Results Nine patients meeting criteria were identified (Table 1). Five patients received alemtuzumab 10 mg IV daily for 5 doses and 4 patients received alemtuzumab 10 mg IV weekly for 4 doses. Median age was 65 (range 34-81) years and the median number of prior regimens was 3 (range 1-5). All (100%) patients were refractory to immunosuppressive therapy. Seven (78%), 1 (11%) and 1 (11%) patients had unilineage, bilineage and trilineage cytopenias, respectively. Five patients (56%) had autoimmune comorbidities and five (56%) required periodic transfusions. No patients had myelodysplasia on bone marrow biopsy. Overall, 6 (67%) patients had a hematologic response with 2 patients achieving a partial response (PR) and 4 patients achieving a complete response (CR). ORR at 3 and 6 months was 56% and 44%, respectively. Two (40%) patients achieved transfusion independence. The 3 patients without a hematologic response were retreated with alemtuzumab 10 mg IV daily for 10 doses with 1 subsequently achieving a CR. At a median follow-up time of 7.2 (range 2.3-36.6) months, 3 out of 6 patients who achieved a response had disease relapse; 8 (89%) patients were alive and 1 had died from COVID-19 pneumonia. Among the 5 patients who received alemtuzumab at 10 mg daily for 5 doses, ORR was 40% with 1 patient achieving PR and 1 patient achieving CR. ORR at 3 and 6 months was 40% and 40%, respectively. One (20%) patient had an infusion reaction. Two patients (40%) had subclinical CMV viremia which resolved with valganciclovir. No cases of EBV viremia were noted. Four patients completed alemtuzumab at 10 mg weekly for 4 doses; ORR was 100% with 1 patient achieving PR and 3 achieving CR. Hematologic response rate at 3 and 6 months was 75% and 50%, respectively. Three (75%) patients relapsed at 3, 4 and 14.2 months, respectively; 2 were retreated 4-6 times with alemtuzumab 10 mg IV weekly for 2 to 6 doses each time, with both achieving hematologic responses with each course of treatment. One (25%) patient experienced an infusion reaction. No cases of CMV or EBV viremia were noted. Conclusions Short-duration alemtuzumab is effective and well tolerated in R/R T-LGL with responses observed in 67% overall and no cases of CMV viremia detected in the weekly dosing group. Alemtuzumab given at 10 mg IV weekly for 4 doses or until a response is noted followed by retreatment upon relapse was particularly effective; this abbreviated, response-adapted alemtuzumab strategy should be prospectively explored in this patient population. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparative effectiveness of neutralising monoclonal antibodies in high risk COVID-19 patients: a Bayesian network meta-analysis

The purpose of this work was to review and synthesise the evidence on the comparative effectiveness of neutralising monoclonal antibody (nMAB) therapies in individuals exposed to or infected with SARS-CoV-2 and at high risk of developing severe COVID-19. Outcomes of interest were mortality, healthcare utilisation, and safety. A rapid systematic review was undertaken to identify and synthesise relevant RCT evidence using a Bayesian Network Meta-Analysis. Relative treatment effects for individual nMABs (compared with placebo and one another) were estimated. Pooled effects for the nMAB class compared with placebo were estimated. Relative effects were combined with baseline natural history models to predict the expected risk reductions per 1000 patients treated. Eight articles investigating four nMABs (bamlanivimab, bamlanivimab/etesevimab, casirivimab/imdevimab, sotrovimab) were identified. All four therapies were associated with a statistically significant reduction in hospitalisation (70–80% reduction in relative risk; absolute reduction of 35–40 hospitalisations per 1000 patients). For mortality, ICU admission, and invasive ventilation, the risk was lower for all nMABs compared with placebo with moderate to high uncertainty due to small event numbers. Rates of serious AEs and infusion reactions were comparable between nMABs and placebo. Pairwise comparisons between nMABs were typically uncertain, with broadly comparable efficacy. In conclusion, nMABs are effective at reducing hospitalisation among infected individuals at high-risk of severe COVID-19, and are likely to reduce mortality, ICU admission, and invasive ventilation rates; the effect on these latter outcomes is more uncertain. Widespread vaccination and the emergence of nMAB-resistant variants make the generalisability of these results to current patient populations difficult.

Tele-chemotherapy and related outcomes to improve rural cancer care.

142 Background: We previously reported the safety and feasibility of tele-chemotherapy with remote administration of chemotherapy (chemo) in rural hospitals using experienced chemo nurses with direct supervision from medical oncologist at a tertiary site. Herein we report the detailed overview of types of cancers treated, chemo-regimens administered and associated outcomes within an integrated health system. Methods: We retrospectively analyzed 200 patients who received chemotherapy remotely in 4 rural health hospitals in the state of Utah between 2017- 2022. Data collected included age of administration of chemo, gender, cancer type, insurance, chemotherapy regimen, number of cycles, emergency visits, hospitalizations, and infusion reactions. Results: 200 pts received chemotherapy at 4 rural hospitals including Sevier Valley Hospital, Cassia Regional Hospital, Sanpete Valley Hospital, and Heber Valley Hospital in Utah and Idaho. Median age of administration was 53 yrs (11- 96 yrs). Majority were male (n = 118; 59%). Insurances that covered these services included Medicare, Medicaid, Regence Blue Cross, United Healthcare, Tricare and Select Health. The most common cancer types treated included – Colorectal (n = 31), Breast (n = 24), Lung (n = 15), Lymphoma (n = 21), Multiple Myeloma (n = 11), Melanoma (n = 9), Bladder (n = 7), and other benign conditions (n = 25). 47 unique chemo regimens including 1085 cycles were administered. Chemo regimens and cycles detailed below. Among 69 pts with outcomes data available, ED visits noted in 33% (n = 23), hospitalization rate was 17% (n = 12) and infusion reaction rate was 7% (n = 5). Total mileage saved by pts receiving chemotherapy closer to home was 47,955 miles. Conclusions: Tele-chemotherapy is safe, feasible and provides improved access to cancer care in rural areas. Future design of pragmatic clinical trials where remote administration of standard of care treatments closer to home will allow the rural pts access cutting edge clinical trials closer to home.[Table: see text]

Rapid infusion of infliximab biosimilars and the incidence and severity of infusion-related reactions in patients with inflammatory bowel disease.

Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar. This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates. A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p=0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p=0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p=0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients). Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.

Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects.

Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n=127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n=123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). Sequential RTX therapy, initiated at a median of 10years [interquartile range (IQR) 7.3-14.4], was administered for 1.8courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3years in patients with steroid-sensitive disease and 2years in those with steroid resistance. Relapses were reduced by a mean of 2.0relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n=108) and infections (n=46); serious adverse events were observed in 10.8% patients, at 0.03events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n=52)] than tetanus [65.5% and 34.5% (n=58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.

244P The incidence of infusion related reactions with trastuzumab-emtansine

Ado-trastuzumab-emtansine (T-DM1) is licensed as palliative and adjuvant treatment for breast cancer. The recommendation is for post-infusion observation of 90 minutes following cycle 1, and 30 minutes for subsequent cycles, owing to the risk of hypersensitivity reactions. The need for observation has significant implications for oncology day unit capacity and patient time in hospital. This study aimed to evaluate the rate and severity of trastuzumab-emtansine infusion reactions in our cohort of patients, to determine if shorter observation times would be safe.