A phase 4 study to evaluate outpatient blinatumomab in patients with minimal/measurable residual disease (MRD) positivity (+) of B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

TPS7051 Background: The prognosis for adults with relapsed or refractory BCP-ALL is poor. MRD+ is the strongest predictor of relapse. Blinatumomab, a CD3/CD19-directed BiTE® (bispecific T-cell engager) molecule, is an effective treatment for patients with MRD+.1 Blinatumomab is administered as a continuous intravenous infusion (cIV) 28 days per cycle. Severe adverse events (AEs) such as cytokine release syndrome (CRS) and neurologic toxicity (NT) may occur; thus, hospitalization is recommended for the first 3 days of cycle 1 and the first 2 days of cycle 2 for MRD+ patients. However, the incidence of severe AEs is low in MRD+ BCP-ALL patients (CRS: 2%, NT: 13%).1 We believe that with the use of effective digital monitoring devices, blinatumomab can be safely administered for the entire 28-day cIV cycle as an outpatient. Methods: Adult patients (n = 45) with BCP-ALL in complete remission and MRD+ (≥0.1% blasts) are being enrolled at 25 planned treatment sites, endpoint: grade ≥3 AE during monitoring (Amgen NCT04506086). Patient suitability for blinatumomab and outpatient monitoring is established. Patients will receive 2-4 cycles of blinatumomab. Cycles are initiated in the outpatient setting, digital monitoring devices activated and attached, and patients sent home. Once home, patients set up the home hub and real-time remote data transfer to the healthcare professional (HCP) begins. The devices are worn continuously, 24 hours a day for the first 3 days of cycle 1 and the first 2 days of cycle 2 only. Devices: Current Health’s Wearable Monitoring System (CHWMS) is an FDA-cleared platform for wireless and wearable health monitoring of patients at home. The CHWMS provides continuous oxygen saturation, respiratory rate, and heart rate; an axillary temperature sensor is worn and provides continuous temperature. Patients manually measure blood pressure every 3-6 hours around the clock. Patients have an integrated mobile device (tablet) to initiate contact with the HCP if needed. HCP/designee has a mobile device (smart phone) and receives vital signs as a constant live feed transmitted from the CHWMS device. The CHWMS platform generates a loud audible alert based on pre-specified vital sign alarming thresholds or if there is an interruption in data transfer. HCP may initiate direct audio and video contact with the patient, assess the patient’s condition, and make an appropriate intervention. HCP may also initiate patient contact in the absence of an alert. Patients are required to have a caregiver present during the entire period of outpatient monitoring. Patients have a full set of replacement devices as well as a 24/7 hotline for device support. Trial enrollment is underway. This study may generate feasibility data on the effectiveness of home monitoring during blinatumomab infusion in patients with MRD+ BCP-ALL. 1Gökbuget, Blood, 2018. Clinical trial information: NCT04506086.

Early prognostication of COVID-19 to guide hospitalisation versus outpatient monitoring using a point-of-test risk prediction score

IntroductionRisk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking.MethodsMultivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290).Results983 patients (median age 70, IQR 53–83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0–1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%).ConclusionThe SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.

Fast and furious: flecainide toxicity presenting as monomorphic ventricular tachycardia

A 63-year-old woman on flecainide, furosemide, and triamterene–hydrochlorothiazide presented with weakness and diarrhoea. She had profound hyponatraemia, hypokalaemia and a pre-renal acute kidney injury (AKI). Her ECG showed a regular wide complex tachycardia concerning for monomorphic ventricular tachycardia. She was haemodynamically stable and treated with aggressive electrolyte repletion and amiodarone. Flecainide toxicity can present as a variety of arrhythmias and early recognition is crucial. This case focuses on flecainide toxicity from multiple concomitant insults: diuretic use, diarrhoea, hypokalaemia, hyponatraemia and pre-renal AKI. We emphasise the importance of close outpatient monitoring of electrolytes in a patient on diuretics and flecainide to prevent life-threatening arrhythmias. We discourage use of multiple diuretics in patients taking flecainide.

Guideline-based and personalized treatment approach to reduce hospitalizations and mortality for high risk advanced chronic systolic heart failure

The aim of our research was to evaluate mortality and rehospitalizations rates in patients with high risk subtype of heart failure (advanced HF) during 12 months of intensive monitoring after discharge on the basis of guidelines recommendations and personalized approach in treatment with frequent outpatient monitoring to reveal subcompensation/worsening of HF. Methods High risk advanced subtype of systolic HF was determined based on at least two hospitalizations during last year, severely reduced EF<30%, right and left atria hypertension echo patterns, pseudonormal/restrictive diastolic dysfunction, frequent outpatient deterioration of euvolemic state. Patients were randomized into two groups: 143 patients who underwent personalized intensive outpatient monitoring with care and 71 patients who underwent standard monitoring with regular guideline based treatment Intensive monitoring in ambulatory settings included frequent attending protocol of clinical evaluation (from OPTIMIZE -HF multicenter study), body mass, heart rate, GFR controls and additional echo evaluation of pressures in right and left atria at every outpatient visit, lung ultrasound with detection of B-lines. Results Cumulative number of CV and HF deaths was 11% (16 out of 143 in intensive monitoring group) and 36% (26 out of 71 patients) in standard monitoring group. Kaplan-Meier curve showed survival benefit in patients with personalized monitoring and treatment compared to those who were on standard care (Picture 1). Conclusions A strong trend towards decline in mortality and rehospitalizations, when personalized outpatient monitoring was implemented was observed (P<0,001) at 12 months in patients with advanced systolic heart failure. Kaplan-Meier survival curves groups Funding Acknowledgement Type of funding source: None