The Year in Electrophysiology: Selected Highlights From 2022.

This special article is the fifth in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors would like to thank the Editor-in-Chief, Dr Kaplan, the Associate Editor-in-Chief, Dr Augoustides, and the editorial board for the opportunity to author this series, which summarizes the key research papers in the electrophysiology (EP) field relevant to cardiothoracic and vascular anesthesiologists. These articles are shaping perioperative EP procedures and practices, such as pulsed-field ablation, cryoablation for first-line treatment for atrial fibrillation, advancements in conduction system pacing, safety issues related to smartphones and cardiac implantable electronic devices, and alterations in EP workflow as the world emerges from the COVID-19 pandemic. Special emphasis is placed on the implications of these advancements for the anesthetic care of patients undergoing EP procedures.

Healthcare-associated infection and antimicrobial consumption in critically ill COVID-19 patients: An observational study

Background: The COVID-19 pandemic has impacted patient and safety issues globally, with special reference to device-associated infection in critical care patients. Objective(s): To describe the incidence of device-associated infections, non-device-associated respiratory tract infections (RTIs), and antimicrobial use in critical COVID-19 patients during the first six months of the pandemic. Method(s): An observational study was conducted in an intensive care unit of a COVID-19-dedicated facility in Western Qatar from April 1 to September 30, 2020. Healthcare-associated infections (HAIs) were confirmed using the CDC definitions as per the corporate infection control program, except for other RTIs. Antimicrobial consumption was registered as days of therapy. Result(s): During the study period, 30 patients (10.9%) with HAIs were reported from 275 patients admitted. Patients with HAI had a higher median Charlson index, hospital stay, mortality, and APACHE II score on admission. The use of devices (central and peripheral lines, urinary catheters, and ventilators) was more frequent in patients with HAI. The RTI (16 cases) and ventilator-associated pneumonia (VAP) (10 cases) were the most frequent localizations. The infection rate for device-associated infections was 7.84, 3.23, and 2.75 per 1000 device days for VAP, central line-associated bloodstream infection, and catheter-associated urinary tract infection, respectively. 49 isolates related to HAI were identified, with 20 isolates being multidrug-resistant organisms (40.8%). A longer duration of antibiotic therapy was observed in HAI patients (34.1 days versus 9.39 days). Conclusion(s): The study provides evidence of the impact of COVID-19 on the incidence of device-associated infections in critically ill patients, antibiotics consumption, and antimicrobial resistance.Copyright © 2022 Garcell, Jimenez, de la Nuez Jimenez, Rivera, Abdi licensee HBKU Press.

Joint Distraction Using An Intended Device For Knee Osteoarthritis: A Prospective Two-Year Follow-Up

Purpose: Knee distraction (KD) treatment for young (<65) patients with end-stage knee osteoarthritis (OA) has previously been shown to successfully postpone a knee arthroplasty for years by reducing pain, improving function, and inducing joint tissue repair. During KD treatment, the tibia and femur are separated ~5 mm for ~6 weeks using an external fixation device. The studies performed thus far have used proof-of-concept medical devices intended for other applications than KD. Recently, the first device specifically designed and intended for KD treatment has been developed. The purpose of the current study was to evaluate the clinical efficacy of this intended device. Method(s): In 5 hospitals, 65 patients with end-stage knee OA, in general practice considered for arthroplasty or high tibial osteotomy, were offered KD treatment by their orthopedic surgeon. Inclusion criteria were judged by the orthopedic surgeon and included age <=65 years, BMI <35 kg/m2 with weight <=110 kg, sufficient knee stability and physical condition, KL grade >=2, malalignment <=10 degrees, no history of inflammatory or septic arthritis. KD was performed according to a standardized protocol. Before and 1 and 2 years after treatment, standardized knee radiographs were performed and patients filled out WOMAC (for pain and function, 0-100, primary clinical outcome) and SF-36 (for quality of life, 0-100, secondary outcome) questionnaires. From the radiographs, minimum joint space width (JSW, mm, primary structural outcome) was measured by one experienced observer and KL grade at baseline was determined. Use of self-reported pain medication (paracetamol, opioids, NSAIDs) and intra-articular injections were registered as well, as were adverse events. Changes over 2 years were evaluated for statistical significance with paired t-tests for continuous variables and McNemar's tests for categorical variables. For the primary clinical outcome (WOMAC), clinical significance was evaluated as well, on group level defined as an increase of >=15 points and on individual level using OARSI-OMERACT response criteria. The influence of adverse effects on 2-year changes in primary outcomes was analyzed with independent t-tests. Result(s): Of the 65 treated patients (age: 53.3+/-6.7;BMI: 28.0+/-3.2;sex: 38 (55%) male;KL grade 0/1/2/3/4: 0 (0%) / 7 (11%) / 26 (40%) / 23 (36%) / 9 (14%)), 50 patients completed 2 years follow-up: 6 patients received partial or total arthroplasty (of which 3 in the 1st year) and 8 patients were lost to follow-up in the 2nd year (primarily due to COVID restrictions). The total WOMAC score (Figure 1A/B) showed a statistically and clinically significant improvement over 1 (+28.4 points;p<0.001) and 2 (+26.2 points;p<0.001) years, as did all the subscales (all p<0.001). After 1 year 72% of patients were OARSI-OMERACT responders, while after 2 years this was 51%. The minimum JSW (Figure 1C/D) significantly improved over 1 (+0.5 mm;p<0.001) and 2 (+0.4 mm;p=0.015) years as well. The physical component scale of the SF36 (Figure 2A/B) showed statistically significant improvement over 1 (+10.5 points;p<0.001) and 2 (+9.8;p<0.001) years, while the mental component scale (Figure 2C/D) did not (both p>0.26). The most common adverse event (Table 1) was pin tract skin infections, experienced by 46 (71%) of patients. In most cases (36;78% of cases) they could be treated with oral antibiotics, while in 3 of the cases (5% of treated patients) hospitalization and/or intravenous antibiotics were needed. Also, 8 (12%) of patients experienced device related complications. Experiencing pin tract infections or device complications did not significantly influence 2-year changes in primary outcomes in these patients (both p>0.05). Before treatment, 39 (60%) of patients used pain medication (Table 2), most often paracetamol (20;31%) or NSAIDs (16;25%). Around half used them daily. After treatment, significantly less patients used pain medication (p<0.001), with 35% at 1 year and 36% at 2 years. In total 12 (18%) patients had received an intra-arti ular injection before KD treatment, of whom 5 (8%) steroids and 3 (5%) hyaluronic acid. Both in the 1st and 2nd year after treatment, 1 patient (2%) received an injection. Conclusion(s): Patients treated with the first device intended for KD treatment showed significant clinical and structural improvement after 1 and 2 years. Importantly, the effect was clinically relevant, as a majority of patients were clinical responders and pain medication use decreased. Long-term evaluation will show whether arthroplasty can be postponed successfully as well. [Formula presented] [Formula presented] [Formula presented] [Formula presented]Copyright © 2023

Single-centre prospective clinical and procedural analysis identifying causes of delay to haematopoietic stem cell transplant in MPS I (Hurler syndrome) patients

The international standard treatment for mucopolysaccharidosis type I - Hurler syndrome (MPS1H) is haemopoietic stem cell transplant (HSCT) preceded by intravenous enzyme replacement therapy (ERT), with HSCT ideally undertaken before 18 months age to achieve best outcome. The invasive nature and high risk of morbidity and mortality associated with HSCT, in addition to a complex patient cohort, demands an extensive pre-transplant work-up to minimise risks where avoidable. This is achieved by collaboration between transplant and specialist paediatric LD-metabolic services. Transplant may be delayed due to clinical complications pre-transplant, but non-clinical disruptions have also been encountered in practice causing delays from time of diagnosis to transplantation. This work aimed to identify clinical complications and non-clinical disruptions in this process, and to identify areas of improvement for clinical practice, ultimately to achieve timely intervention and optimise clinical outcomes. A single-centre prospective clinical and procedural analysis of 7 MPS1H patients undergoing HSCT between April 2020 - January 2021 was completed. Age at diagnosis (median(range)) was 10 (1.5–25) months. Time from diagnosis to starting ERT (median(range)) was 10 (3–26) days. Time from diagnosis to transplant (median(range)) was 158 (101–189) days, with age at transplant 14 (6.5–30) months. Multiple reasons causing delay were identified. Clinical factors included presence of dilated cardiomyopathy, requirement for adenotonsillectomy to treat obstructive sleep apnoea, Covid-19 infection, vascular device infection, and acute neurosurgical issues including hydrocephalus requiring ventriculoperitoneal shunt and cervical spine stenosis requiring decompression. Non-clinical factors identified included late cancellation of required investigations, missed clinic appointments, and issues with accessing HSCT donors due to UK/European political situation and Covid-19 restrictions. Clear communication between teams was found to be a key identifying factor in ensuring timely completion of the pre-HSCT.

The Impact of the COVID-19 Pandemic on Hospital-Acquired Infections at a Comprehensive Cancer Center

Background. Robust infection control (IC) measures were deployed across healthcare institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment (PPE), enhanced contact precautions, and emphasis on hand hygiene. The impact of these IC measures on the rates of hospitalacquired infections (HAIs), such as multidrug-resistant organisms (MDROs), device-related infections (DRIs), Clostridium difficile infection (CDI), and respiratory viral infections (RVIs) is not known. Here, we aim to evaluate the effect of the enhanced IC practices on the occurrence of various HAIs in a comprehensive cancer center. Methods. We analyzed the monthly HAIs rates from September 2017 through March 2022, including data 42 months pre-pandemic (September 2016-February 2020) and 24 months during the pandemic (March 2020-August 2021). Reported HAIs were calculated using denominators of patient days for CDI and MDROs, per 1,000 admissions for RVIs, and catheter days for DRIs. The incidence rate ratios (IRR) were calculated for all HAIs. Results. When comparing pre-pandemic to the pandemic period, a significant increase in the overall incidence rate (IR) of MDROs from 0.56 to 0.67 per 1,000 patient days with an IRR of 1.19 (95% CI 1.02-1.39), a decrease in the IR of CLABSIs and a stable IR of CAUTIs and VAEs were observed (Table 1). A significant decrease was observed in the IR of CDI (IRR 0.65 (95% CI 0.55-0.78)). The total IR of hospital-acquired RVIs per 1,000 admissions (5.24 to 1.82;IRR 0.36;95% CI 0.30-0.44) decreased, as did each respiratory virus (Respiratory Syncytial Virus (0.51 to 0.15;IRR 0.30), Influenza (0.50 to 0.24;IRR 0.50), Parainfluenza (1.21- to 0.34;IRR 0.28), Rhinovirus (1.91 to 0.5;IRR 0.26), and Human Metapneumovirus (0.19 to 0.05;IRR 0.24) during their respective respiratory viral seasons (Figure 1). (Table Presented) Conclusion. Implementing strict IC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs. However, whether these enhanced measures, such as masking at all times as part of patient care, are needed during the upcoming respiratory viral seasons is not known.

Erosion of Inflatable Penile Prosthesis with Prolonged Foley Catheterization in the COVID-19 Era

Introduction: The COVID-19 pandemic has changed the lives of many in the past year. As of writing this article, the virus has claimed over half a million American lives and has infected millions more. It has affected many people regardless of age, gender, race, religion, or medical history. We have noticed a unique sequence of events in urology patients with a prior history of inflatable penis prothesis implantation who have gotten critically ill from the SARS-CoV-2 virus. Objective: We report our experience with patients with an inflatable penile prothesis who suffered respiratory failure due to the SARS-CoV-2 virus and findings that would help limit the risk of implant infection and/or erosion if prolonged urethral catherization is needed. Methods: We have encountered 3 patients with a very similar history in the past year. They were all men aged 57-72 years old who had a functioning inflatable penile prothesis (IPP) for many years (3-13) and were intubated for a prolonged period of time (2-4 weeks) after suffering respiratory distress from the SARS-CoV-2 virus. During this time, they all had a prolonged urethral Foley catherization for urinary drainage while in the ICU. They were all subsequently found to have urethral erosion of a penile implant cylinder which was not present prior to hospitalization. Their charts were reviewed. Results: Two patients underwent explantation of their IPP during their hospital stay and one presented to our outpatient office 2 months after discharge with the complaint of urethral cylinder erosion and underwent subsequent explantation. Conclusions: Urethral catheterization is commonly used in the intensive care unit and spinal cord injury patients due to their convenience and efficacy. The friction and inflammation created by prolonged transurethral catheterization can be disastrous for IPPs by increasing the likelihood of infection and/or device erosion. In fact, Steidle and Mulcahy found that five out of their nine patients (55%) with IPPs who had an indwelling or intermittent transurethral catheterization were eventually found to have erosion of their IPP. In addition, indwelling transurethral catheters also confer a higher risk of urinary tract infection. Han et al. found that suprapubic tube placement conferred a statistically significantly lower risk of urinary tract infection when compared to indwelling transurethral catheterization for over five days at an odds ratio of 0.142 (95% CI 0.073-0.0276). Another alternative to bladder drainage in the intubated IPP patient is clean intermittent catherization (CIC), however this poses a unique challenge in the intubated COVID positive patient as it repeatedly exposes healthcare staff the virus-carrying patient. When compared to indwelling transurethral catherization, suprapubic tube placement has been shown to confer a lower risk of urinary tract infection and IPP infection/erosion. This can primarily be explained by its ability to drain the bladder without creating inflammation and friction in the urethra. Therefore, we propose that any team caring for a patient with an IPP and a planned, prolonged indwelling transurethral catheterization consult urology services to have a suprapubic tube temporarily placed. This will ensure that the risk of urinary tract infection and/or IPP erosion is kept as low as possible. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific, Neotract

Physiologic changes of covid-19 infection detected by cardiac implantable electronic device data

Background: The trajectory of cardiac physiology throughout a COVID-19 infection remains poorly described. This study aimed to characterize physiologic changes associated with acute COVID-19 infection among patients with cardiac implantable electronic devices (CIEDs). Methods: The study population included 286 patients with a Boston Scientific CIED across a large health system. CIED sensor data from March 2020-February 2021 were linked to clinical data from electronic health records. Three cohorts were created: COVID-positive (n=20), COVID-negative (n=166), and an untested control (n=100) to account for testing bias as institutional protocols only allowed symptomatic patients to be tested in the early months of the study. The magnitude of sensor changes from baseline (30-60 days before a COVID-19 test) to event (15-day window around a test) was compared between cohorts using one-way ANOVA. A date during the study window was randomly selected to serve as the event for control cases. Results: Comparing COVID-positive vs. COVID-negative vs. control, there was a greater change from baseline to event in respiratory rate (15% vs. 2% vs. 0.6% [p<0.0001]), activity (-44% vs.-12% vs.-6% [p<0.0001]), temperature (1% vs. 0.1% vs.-0.3% [p<0.0001]), and HeartLogic Index, a composite index using multiple sensors (227% vs.-11% vs. 2% [p=0.004]). Average sensor changes show prominent differences surrounding a COVID-19 test for COVID-positive compared to COVIDnegative and control cases (Figure). Conclusions: Physiologic changes associated with COVID-19 infection are detectable using CIEDs. COVID-positive patients have significant increases in respiratory rate, temperature and HeartLogic index and significant decreases in activity compared to COVID-negative and untested patients. Future studies in a larger population will help characterize the utility of CIEDs in infection surveillance and physiologic worsening that should prompt medical attention.

Efficacy and Safety of Fitusiran Prophylaxis, an siRNA Therapeutic, in a Multicenter Phase 3 Study (ATLAS-INH) in People with Hemophilia A or B, with Inhibitors (PwHI)

Introduction Hemophilia A and B are rare bleeding disorders characterized by ineffective clot formation due to impaired thrombin generation as a result of deficiency of FVIII or FIX, respectively. Fitusiran is a subcutaneously (SC) administered investigational siRNA therapeutic targeting antithrombin to restore thrombin generation and rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Here, we present the safety and efficacy of fitusiran prophylaxis for PwHI in a phase 3 study (ATLAS-INH;NCT03417102). Methods The ATLAS-INH study is a randomized, open-label Phase 3 study designed to evaluate the efficacy and safety of fitusiran in PwHI. Eligible males ≥12 years receiving on-demand treatment with bypassing agents (BPA) were randomized in a 2:1 ratio to receive once monthly 80 mg SC fitusiran prophylaxis or continue with on-demand BPA. The primary endpoint is annualized bleeding rate (ABR) in PwHI on fitusiran prophylaxis compared to those on BPA on-demand in the efficacy period. The secondary endpoints include spontaneous ABR, joint ABR, and quality of life (QoL) measured by Haem-A-QoL. Results 57 subjects were randomized into the study. Mean (range) age of the study participants at screening was 28.4 (13-63) yrs. Statistical significance was achieved for primary and all secondary endpoints with significant reduction in ABRs of treated bleeds: all, spontaneous and joint bleeds for fitusiran vs on-demand BPA arm (Table 1). A total of 25 patients in fitusiran arm (65.8%) had zero treated bleeding events. Efficacy of fitusiran prophylaxis treatment was seen in both hemophilia A and hemophilia B patients with inhibitors. Statistical significance was also achieved for improvement in physical health domain score, with a difference (95% CI) of -28.72 (-39.07 to -18.37, p-value <0.0001) as well as overall HRQoL and between fitusiran and on-demand BPA arms. Overall, 38 patients (92.7%) in the fitusiran arm and 11 patients (57.9%) in the on-demand BPA arm experienced at least 1 treatment emergent adverse event (TEAE). A total of 13 treatment emergent serious adverse events (TESAEs) were reported in 7 patients (17.1%) in the fitusiran arm and 8 TESAEs were reported in 5 patients (26.3%) in the on-demand BPA arm. All TESAEs were reported in 1 patient each;in the fitusiran prophylaxis arm these included events of device related infection, hematuria, spinal vascular disorder, subclavian vein thrombosis, thrombosis, acute cholecystitis, chronic cholecystitis and asymptomatic COVID-19. One patient (2.4%) in the fitusiran arm experienced TEAEs that resulted in study drug discontinuation (spinal vascular disorder and thrombosis). There were no fatal TEAEs reported. Conclusions This Phase 3 study demonstrated the efficacy of the 80 mg monthly subcutaneous prophylaxis dose of fitusiran in people with hemophilia A or B with inhibitors. Specifically, fitusiran significantly reduced bleeding with a median ABR of zero and significant proportion of people with zero bleeds, resulting in a meaningful improvement in health-related quality of life. Reported TESAEs were generally consistent with what is anticipated in an adult and adolescent population with severe hemophilia A or B with inhibitors, or with the previously identified risks of fitusiran. A revised fitusiran dosing regimen with reduced dose and dose frequency is currently being evaluated in ongoing clinical studies. [Formula presented] Disclosures: Young: Genentech/Roche, Grifols, and Takeda: Research Funding;Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy. Kavakli: Roche: Consultancy, Other: Clinical Trial Support;Novo Nordisk A/S: Consultancy, Other: Clinical Trial Support;Takeda: Consultancy, Other: Clinical Trial Support. Poloskey: Sanofi: Current Employment, Current equity holder in publicly-traded company. Qui: Sanofi: Current Employment, Current equity holder in publicly-traded company. Kichou: Sanofi: Current Employment, Current equity holder in publicly-tr ded company. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company;WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Mei: Sanofi: Current Employment, Current equity holder in publicly-traded company. Rangarajan: Sanofi: Other: Advisory Board;Pfizer: Other: Advisory Board;Reliance Life Sciences: Consultancy;Takeda: Other: Advisory Board, Conference Support, Speakers Bureau.

A Phase 1b Study of Blinatumomab Including Subcutaneous Administration in Relapsed / Refractory (R/R) Indolent Non Hodgkin's Lymphoma (NHL)

Background: Blinatumomab, a bispecific T-cell engager (BiTE ®) molecule that directs cytotoxic T-cells to lyse CD19-expressing B lineage cells, has been investigated in NHL (Goebeler JCO 2016, Viardot Blood 2016, Katz ASH 2019). Here, we evaluated subcutaneous (SC) blinatumomab, which may simplify administration, improve convenience, and potentially reduce adverse events (AEs). Methods: Patients (pts;≥18 y) had indolent NHL (follicular, marginal zone, lymphoplasmacytic, mantle cell, or small lymphocytic) that was primary refractory (1+ prior line), relapsed (within 1 y of first response), or that had responded to initial therapy for ≥1 y and relapsed after 2+ lines, including an anti-CD20 monoclonal antibody. Disease must not have been irradiated and was measurable (≥1.5 cm) on PET-CT or CT. Pts had a 3-wk continuous intravenous (cIV) run-in period followed by SC dosing in 5 cohorts, a further 2 wks of cIV dosing, and the option for a second cycle of cIV dosing (Figure). The primary objective was safety and tolerability of SC blinatumomab;secondary objectives included pharmacokinetics (PK), estimating the maximum tolerated dose (MTD), ie, the highest dose at which ≤1/6 pts had a dose-limiting toxicity (DLT), and efficacy (NCT 02961881). Results: Pts (n=29) had a median (range) age of 64 (42-75) y, 55% were male, 90% Caucasian, with follicular I-IIIA (76%), marginal zone (10%), mantle cell (10%) and lymphoplasmacytic lymphoma (3%) subtypes;no pts had prior allo-hematopoietic stem cell transplant (HSCT), 38% had prior auto-HSCT. Of the 29 pts, 5 discontinued (D/C) blinatumomab due to AEs (n=3;2 cIV, 1 SC), pt request (1), and disease progression (1);no pts D/C due to COVID-19 control measures;26 pts completed the study;pts received a median (range) of 5 (3-10) doses. AEs leading to D/C in SC treatment included neurologic events of aphasia and seizure. During SC dosing, 2 DLTs occurred (aphasia, n=1;seizure, n=1 ). MTD was not reached. Five pts had grade 3 (G3) AEs (thrombocytopenia, erosive esophagitis, asthenia, device-related infection, hyperglycemia, aphasia, seizure;pts may have had >1 G3 AE);there were no G4 AEs or fatal AEs. AEs of interest included neurologic events (all, n=15;G3, n=2), infection (2;1), and cytokine release syndrome (4;0). One pt had grade 1 injection site erythema. Anti-blinatumomab antibodies have not been detected to date. Preliminary PK results were consistent across the 5 SC cohorts and 3 different dosing regimens. Following the first dose, maximum concentrations (C max) were reached after ~5-12 hours and exposures (C max and area under concentration-time curve [AUC] from 0-12 hours) increased in a dose-related manner. At steady state, exposures (AUC over the dosing interval) increased in a dose-related manner for dosing intervals of once every 12, 24, and 48 hours across cohorts. Blinatumomab bioavailability and apparent terminal elimination half-life were favorable for extending the dosing interval to once every other day and potentially longer intervals. The steady-state concentrations during both cIV infusion periods were consistent with those previously reported in NHL pts. In all pts, the overall response rate (ORR, representative of cIV, 5 wks and SC, 1wk) per Cheson criteria was 69% (evaluable, n=23: complete response [CR], 21%;partial response [PR], 48%;cycle 1 [C1], n=22: ORR, 62%;CR, 14%;PR,48%;cycle 2 [C2], n=17: 45%;17%;28%;respectively);per Lugano criteria, the ORR was 52% (n=21: CR, 24%;PR, 28%;C1, n=18: 45%;17%;28%;C2, n=12: 31%;21%;10%);for follicular lymphoma, ORR was 77% per Cheson (n=19: CR, 23%;PR, 55%) and 55% per Lugano (n=15: CR, 23%;PR, 32%). Conclusions: In pts with R/R indolent NHL, SC blinatumomab had a favorable safety profile, with the caveat that pts who could not tolerate cIV blinatumomab did not advance to SC dosing. Efficacy was comparable with that seen for cIV dosing in prior blinatumomab NHL studies. In contrast to prior blinatumomab trials, no dose dependency in efficacy or toxicity was observed because SC dosi g was administered for only 1 wk, after 3 wks of cIV;pts not tolerating cIV did not receive SC dosing. Safety/tolerability of blinatumomab SC administration over the whole cycle is currently being evaluated in a phase 1 trial of pts with R/R acute lymphoblastic leukemia (NCT 04521231). SC blinatumomab PK, including bioavailability and half-life, showed promising features, warranting further investigation. [Formula presented] Disclosures: Rossi: Astellas: Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Alexion: Membership on an entity's Board of Directors or advisory committees;Sanofi: Honoraria;Takeda: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Daiichi Sankyo: Consultancy, Honoraria;Janssen: Membership on an entity's Board of Directors or advisory committees;Jazz: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees. Prince: Takeda: Consultancy, Honoraria;Amgen: Honoraria, Research Funding;Novartis: Honoraria. Tam: Janssen: Consultancy, Honoraria, Research Funding;BeiGene: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria, Research Funding;Loxo: Consultancy;Roche: Consultancy, Honoraria;Novartis: Honoraria;Pharmacyclics: Honoraria. Ku: Roche: Consultancy;Genor Biopharma: Consultancy;Antegene: Consultancy. Thieblemont: Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Hospira: Research Funding;Bayer: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Popplewell: Pfizer: Other: Travel;Hoffman La Roche: Other: Food;Novartis: Other: Travel. Wermke: Novartis, Roche, Pfizer, BMS: Consultancy, Honoraria, Research Funding. Haioun: Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company);Janssen-Cilag: Consultancy;Celgene: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company);Novartis: Honoraria;Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company);Servier/Pfizer: Honoraria;Gilead Sciences: Consultancy, Honoraria;Takeda: Consultancy;Miltenyi Biotec: Consultancy. Viardot: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees;University Hospital of Ulm: Current Employment. Ferreri: Pfizer: Research Funding;x Incyte: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Genmab: Research Funding;BMS: Research Funding;Hutchison Medipharma: Research Funding;PletixaPharm: Membership on an entity's Board of Directors or advisory committees;Adienne: Membership on an entity's Board of Directors or advisory committees;ADC Therapeutics: Research Funding;Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding;Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding;Ospedale San Raffaele srl: Patents & Royalties;Beigene: Research Funding. Wong: Amgen: Current Employment;Amgen: Current equity holder in publicly-traded company. Kadu: IQVIA: Current Employment. Zugmaier: Amgen: Current Employment;Micromet/Amgen: Patents & Royalties: Patents 20190300609 and 20130323247 licensed;receives royalties of family members of international applications published as WO2010/052014;WO2010/052013;WO2011/051307;WO2012/055961;WO 2012/062596;WO2014/122251;and WO2015/181683;Amgen: Current equity holder in publicly-traded company. Zeng: Amgen: Current Employment, Current equity holder in publicly-traded company. Rambaldi: Celgene: Other: Travel, Accommodations, Expenses;Jazz Pharmaceuticals: Consultancy;Astellas Pharma: Consultancy;Novartis: Consultancy;Omeros: Consultancy, Honoraria;Amgen: Consultancy, Honoraria. OffLabelDisclosure: Blinatumomab is approved in the United States for administration as a continuous intravenous infusion. It has not been approved for subcutaneous administration.