Inclusion In Registry Research Articles

Real World Data of Axicabtagene Ciloleucel As Second Line Therapy for Patients with Large B Cell Lymphoma: First Results of a Lysa Study from the French Descar-T Registry

Background and Significance: Axicabtagene ciloleucel (axi-cel) has demonstrated superior efficacy as second-line therapy (2L) over standard of care chemo-immunotherapy in transplant-eligible patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). In ZUMA-7 trial, 180 patients were randomized to receive axi-cel in 2L, achieving an estimated 4-year overall survival of 54% after a median follow-up of 47 months. In the ALYCANTE phase II study, 62 transplant-ineligible patients with R/R LBCL were treated with axi-cel as 2L, resulting in a 3-month complete metabolic response rate of 71% with a median progression free survival of 11.8 months. Here, we report the first real-world data of axi-cel as 2L for patients with early R/R LBCL treated in French centers. Study Design and Methods: DESCAR-T is a French nationwide registry collecting real-life data of all patients treated with approved CAR T-cell therapies (NCT04328298). All patients were informed before inclusion in the registry. The goal of the present analysis was to describe patients' characteristics, treatment course, and outcomes of all patients consecutively included in DESCART registry since July 2022, and infused with axi-cel according to the early access program supported by French authorities for patients with LBCL in early relapse (< 1 year) or refractory after a first line treatment. Results: Between July 2022 and March 2023, axi-cel was ordered and leukapheresis was performed for 85 patients. The first axi-cel infusion was performed in September 2022 and enrollment increased rapidly with 51 new patients waiting for a leukapheresis at the time of data cut-off in March 2023. No manufacturing failures occurred, at the data cut-off, 78 patients were infused with axi-cel in 22 centers, and 7 patients died before axi-cel infusion (5 because of progression, 2 from other cause). Among the 78 patients infused, 48 (61.5%) were male, median age was 60 years (range: 23-79), 35% were over 65 years old and 5% over 70 years old. Most patients had primary refractory disease (n = 58, 74.3%), a good performance status (n = 62, 79.5% ECOG 0-1), stage III-IV disease (n = 59, 75.6%) and elevated LDH (n = 48, 61.5%). The median time between leukapheresis and axi-cel infusion was 36 days, and 65 patients (83%) received bridging therapy, primarily immuno-chemotherapy (n = 57, 73%). At the time of lymphodepletion, patients had progressive (n = 35, 54%) or stable disease (n = 6, 9%), with only 23 patients (29%) responding to bridging therapy. The median follow-up since CAR-T-cells infusion was 1.1 month (range: 0-6). Safety information was reported for 65 patients: CRS occurred in 95% of patients, however only 3 patients (<5%) had a grade 3 or higher CRS. Neurotoxicity occurred in 43% of the cases, with 6 patients (9%) presenting grade 3 or higher toxicity. Furthermore, 13 patients (21%) were transferred to intensive care unit. Four patients (5%) died, 3 from lymphoma progression (missing data for the remaining patient). Among the 52 patients with at least 1 month of follow-up: the overall response and complete response rates at 1 month were 76.9% and 57.7% respectively (Figure 1). Conclusion: These preliminary results demonstrated that axi-cel in 2L for R/R LBCL is feasible and safe in real-life for transplant and non-transplant eligible patients. Although follow-up of our population remains short, early assessments of response are in line with those described in ZUMA-7 study. Inclusion in DESCART registry is on-going and updated results with at least 3 months of follow-up since infusion will be presented at the meeting.

Trends in outcome and patient composition in dilated cardiomyopathy in Sweden over time

Abstract Background We studied prognosis and patient composition over time in dilated cardiomyopathy (DCM): a well-defined category of heart failure (HF), often affecting younger individuals. We expected improved prognosis over time, due to emerging diagnostic and therapeutic options. Methods All patients from the Swedish Heart Failure Registry (SwedeHF) fulfilling criteria for DCM (exclusion of ischemic, valvular, or alcoholic etiology and affirmed by clinical judgment in the protocol) (n=3739), were analyzed with respect to three time periods of inclusion in the registry, 2003–2007 (n=814), 2008–2011 (n=1448), 2012–2016 (n=1477), regarding mortality, transplantations, and hospital admissions during one year after inclusion. Results Over the three time periods, registered cohorts were older with time (mean 59.3 years/ 60 years/ 61.0 years, p=0.0035), and the proportion of females incresased (24.1% / 27.2% / 30.7%, p=0.0006). For clinical variables, the distribution of left ventricular ejection fraction (LVEF) with time showed significantly higher LVEF (p=0.0024), and functional classification (NYHA) showed lower class (p=0.0011). Hypertension as a comorbidity (i.e. not judged to be responsible for HF) was more frequently occurring with time: (34.0%/ 40.6%/ 44.1%, p<0.0001). As for HF treatment: use of device increased (p<0.0001 for categorical combinations), mineralocorticoid receptor antagonists (MRA) increased (41.9%/ 37.3%/ 46.7%, p=0.0023), and diuretics dropped (76.1%/ 71.1%/ 67.0%, p≤0.0001) in the different cohorts with time. Mortality (6.9%, 5.1%, 5.5%), transplantation (0.5%, 0.8%, 0.6%) and hospital admissions for HF (28.4%, 26.3%, 24.6%) were stable over time (ns for all), whereas cardiovascular (CV) (33.8%, 33.8%, 29.7%, p=0.043) and all cause admissions (39.1%, 38.8%, 33.7%, p=0.0099) decreased. After adjustment for age, sex, LVEF, NYHA, hypertension and device treatment only all cause admissions remained significantly decreased. Conclusion In this nationwide study between 2003–2016, one-year outcome in DCM in Sweden remained stationary over time, despite advances in HF therapy. During the time period, we observed a continuous change in the clinical profile in the DCM population. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Region Västra Götaland agreement concerning research and education of physicians.

355 Assessing the Prognostic Value of Lactate Levels in the Presence of Ethanol Among Emergency Department Patients

Presence of ethanol (EtOH) may alter the relationship between clinically measured lactate concentrations and mortality. This study will assess how the prognostic value of serum lactate concentrations changes based on the presence of EtOH. We performed a retrospective cohort study including all patients, age > 17 years, presenting from January 2012 through December 2018, to an urban, academic emergency department (ED). Patients without ED lactate measurements were excluded. Data were electronically abstracted from the medical record, including demographics, initial lactate level, blood and urine EtOH levels, administration of antibiotics, inclusion in trauma registry, vasopressor administration and 28-day in-hospital mortality. We manually abstracted data from 1000 randomly selected cohort patients to test reliability of the automated abstraction process. The primary outcome was 28-day in-hospital mortality. Initial ED lactate levels were re-grouped using 1.0 mmol/L unit intervals: 0.0-0.9, 1.0-1.9, 2.0-2.9, 3.0-3.9, 4.0-4.9, 5.0-5.9, 6.0-6.9, 7.0-7.9, and >8.0 mmol/L. EtOH levels were grouped as Present (any EtOH present), Absent (EtOH level measured and not detected), and Missing (not ordered). Available urine EtOH levels were utilized if blood EtOH was absent. Using logistic regression and a priori selected mortality risk factors, we created a baseline model to predict 28-day in-hospital mortality for the entire cohort. Among patients with ED lactate measured, we calculated marginal probabilities for mortality, beyond the baseline model, for each lactate interval, using 95% confidence intervals to assess differences. Over seven years, 441,613 adult patient encounters occurred, and 40,956 (9.27%) patients had lactate measured: 4,219 (10.30%) EtOH Present, 11,181 (27.30%) Absent, and 25,556 (62.40%) Missing patients. Overall, 2374 (5.8%, 95% CI 5.6-6.0%) had 28-day in-hospital mortality and this varied by EtOH group: 201 (4.8%, 4.1-5.5%) Present, 916 (8.2%, 7.7-8.7%) Absent, and 1257 (4.9%, 4.7-5.2%) Missing patients. In EtOH Present patients, 3511 (83.2%, 82.1-84.3%) had initial lactate >2.0 mmol/L compared to 4975 (44.5%, 43.6-45.4%) of Absent patients. In logistic regression, after controlling for other predictors of mortality, lactate intervals predicted a higher marginal probability of mortality in the EtOH Absent group compared with Present, until lactate exceeded 6.0 mmol/L: 1.0-1.9 (1.77% (95% CI: 1.42-2.12%) vs 0.27% (0-0.54%)); 2.0-2.9 (2.42% (1.89-2.96%) vs 0.43% (0.16-0.70%)); 3.0-3.9 (1.72% (1.19-2.26%) vs 0.67% (0.29-1.05%)); 4.0-4.9 (2.95% (2.00-3.91%) vs 1.08% (0.41-1.75%)); 5.0-5.9 (3.12% (1.89-4.36%) vs 1.02% (0.30-1.74%)); 6.0-6.9 (3.41% (1.79-5.03%) vs 1.51% (0.32-2.70%)). EtOH may diminish the relationship between initial lactate levels and 28-day in-hospital mortality, decreasing lactate’s prognostic utility in the ED. Clinicians using lactate to risk stratify patients should use caution in the presence of EtOH.

Abstract 169: A Retrospective Cardiovascular Disease Registry to Inform Community Prevention

Background: Cardiovascular disease (CVD) registries are essential to planning, implementation, and evaluation of clinical and public health practice. Registries primarily enroll patients seeking medical care and poor, socially isolated and medically underserved populations are not well represented, distorting the magnitude of the problem and mischaracterizing victims. Lincoln Project investigators contend a retrospective CVD victim registry, created from a well-documented cohort of all-cause Out of Hospital Premature Death (OHPND) victims, dominated by cardiovascular deaths, will accurately identify, describe and locate CVD victims and drive intervention strategies targeting CVD risk factors in the community. Objective: To establish a comprehensive retrospective CVD registry from a cohort of OHPND victims in rural Eastern North Carolina. Methods: All deaths (12,665) for 2014 from 29 counties in Eastern North Carolina (Population 1.5M) were electronically filtered. 1122 cases of OHPND (18-74 years old, natural causes, that died out of the hospital) were identified. Cancer deaths were excluded. Medical records from clinical providers, Emergency Medical Services (EMS) and the Medical Examiner (ME) were procured. Cases were mapped using victim’s residence address and matched with Census data to determine socioeconomic status. All available medical records and reports of OHPND victims were reviewed by a group of 3 cardiologists to determine inclusion in CVD registry per internally designed protocol. Results: Death registration data was acquired for all 1122 OHPND subjects. Medical provider records were available for 71.9% (807/1122) of victims; we captured EMS records on the date of death for 67.2% (755) of victims and all EMS encounter data for three years prior to death on 89.2% (I1001)of decedents. Report of Medical Examiner was available on all (39%) ME cases. No medical records were available for 124 subjects. Of 998 OHPND subjects with available medical records, 659 (66%) met the criteria for inclusion in CVD registry. Of CVD registrants, 66.1% (435/659) had coronary artery disease, 72% (475) hypertension, and 55.2% (364) had diabetes mellitus. Heart failure accounted for 19.3% (127) of registry deaths; resuscitation was attempted on 27.9% (184) of victims, no ROSC was recorded in cases where ressucitation was attempted. GPS mapping of residence addresses shows CVD victims cluster in low socioeconomic areas. Conclusion: A CVD registry, created from a data-rich cohort of OHPND victims, will identify high-risk communities and illuminate common antecedents and modifiable CVD risk factors. Intensive community preventative health care efforts can be initiated to minimize the undue burden of CVD on rural populations.

The socioeconomic profile of a Barrett’s oesophagus cohort assessed by the 2010 Index of Multiple Deprivation

Several reports have described the relationship between socioeconomic status and oesophageal adenocarcinoma but only one with its precursor condition, Barrett's oesophagus. We therefore investigated such an association. The majority (88%) of patients diagnosed with Barrett's at Rotherham District General Hospital between 28 April 1978 and 31 August 2012 consented to inclusion in the UK Barrett's Oesophagus Registry. Those residing within Rotherham form the basis of this study. We assessed socioeconomic status using the Index of Multiple Deprivation 2010 scores which can be assigned to every English postcode. The scores for the whole of England were divided into five equal groups; those of the 6257 postcodes within Rotherham (including those of Barrett's patients) were compared against the national quintile relevant to their score. We examined the ratio of observed against expected numbers of Barrett's in each quintile before and since 2001, the median year of diagnosis. The study group comprised 1076 patients with Barrett's oesophagus. Before 2001 their distribution across the deprivation quintiles was similar to that expected. Since then it has changed significantly, with 37% more Barrett's patients than expected among the two least deprived quintiles, but 11% fewer than expected in the larger population comprising the two most deprived quintiles (P=0.0001). There was no significant difference in the distribution of sex (P=0.27), nor the mean age at diagnosis between the two time periods (P=0.92). Since 2001, there has been a major change in the distribution of Barrett's in relation to socioeconomic status, measured by the Index of Multiple Deprivation.

Treatment Patterns and Outcomes in Patients With Hepatocellular Carcinoma Stratified by Stage-Guided Treatment Categories.

The purpose of this study was to assess the survival and treatment patterns of hepatocellular carcinoma (HCC) stratified by the NCCN stage-guided treatment categories in the absence of a universally accepted staging system for HCC. Patients with HCC were identified using ICD-9 codes and inclusion in the Huntsman Cancer Institute tumor registry. Patients were stratified by the NCCN groupings around the time of diagnosis as potentially resectable or operable (RESECT), potentially transplantable (TRANSP), unresectable (UNRESECT), inoperable due to performance status (INOPER), or having metastatic (METAST) disease. Survival and treatment patterns were assessed by NCCN stage-guided treatment categories. A total of 221 patients (72.9% men) with HCC were identified. At the time of diagnosis, patients were categorized as RESECT (n=28, 12.7%), TRANSP (n=33, 14.9%), UNRESECT (n=77, 34.8%), INOPER (n=40, 18.1%), and METAST (n=38, 17.2%). Staging information was not specified for 5 patients (2.3%) even after chart review. Kaplan-Meier analysis demonstrated significant differences in survival between RESECT and UNRESECT categories, and between UNRESECT and METAST categories. The median survivals in RESECT, TRANSP, UNRESECT, INOPER, and METAST categories were 594, 562, 247, 167, and 44 days, respectively. Patients considered RESECT most frequently underwent resection (61%, n=17) and patients considered TRANSP had the highest use of liver transplants (33.3%, n=11). Use of any treatment was low in the METAST (31.6%, n=12) and INOPER (60.0%, n=24) groups. Treatment patterns in the NCCN groupings correlated with recommended treatment strategies. Overall, the NCCN groupings have a linear relationship in overall survival.

Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network Encephalopathy Registry

Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE. To identify antecedents in a large registry of infants who had NE. This was a maternal and infant record review of 4165 singleton neonates, gestational age of ≥ 36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry. Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of ≤ 3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of ≥ 37.5 °C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination. Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained.