Real-World Study of the Treatment Patterns of Patients Diagnosed with Therapy-Related AML or AML-MRC in England between 2013 and 2020 Using the Cancer Analysis System Database

Introduction: Patients with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) are a known high-risk AML subgroup with historically poor outcomes. In December 2018, CPX-351 (Vyxeos ® Liposomal) received a positive reimbursement decision in England for the treatment of adults with newly diagnosed t-AML or AML-MRC. The objective of this retrospective study was to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics, clinical characteristics, and treatment pathways for patients with t-AML or AML-MRC in England from 2013 to 2020, including the use of CPX-351. Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with t-AML or AML-MRC between January 2013 and March 2020 were identified either directly using International Classification of Diseases for Oncology, Third Edition(ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with a record of prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC; other AML-MRC subtypes could not be distinguished from de novo AML). First-line and second-line treatments identified included clinical trials, intensive chemotherapy (IC) treatments (CPX-351; daunorubicin plus cytarabine [DA]; fludarabine, cytarabine, idarubicin and granulocyte-colony stimulating factor [FLAG-Ida]; or "other IC" consisting of mitoxantrone-based therapy or high-dose cytarabine alone), or less-intensive therapies (azacitidine, low-dose cytarabine [LDAC], or hydroxycarbamide alone). Patients who did not receive active systemic therapy (ie, those who received best supportive care alone) were not included. Results: A total of 2,891 patients with t-AML or AML-MRC were identified. Most patients were male (62%), white (91%), and aged ≥60 years (80%). Overall, 590 (20%) patients received first-line treatment in a clinical trial, 1,474 (51%) received less-intensive therapy, and 827 (29%) received an IC regimen. Patients aged ≥60 years at diagnosis were less likely than those aged <60 years to either enter a clinical trial (18% vs 32%, respectively) or receive IC (22% vs 54%). In patients treated with IC, those who received CPX-351 were slightly older (mean [standard deviation] age: 63.9 years [8.3]) than those who received DA (60.5 years [11.4]) or FLAG-Ida (55.6 years [12.6]); 28% of patients treated with CPX-351 were aged <60 years compared to 37% for DA and 55% for FLAG-Ida. When treatment patterns were analyzed per annum, utilization of less-intensive therapies remained stable over time (Figure 1A). Azacitidine was the most common less-intensive therapy both overall (64%) and across all yearly time points, followed overall by LDAC (22%) then hydroxycarbamide alone (14%). In contrast, the IC treatment patterns were more dynamic over time (Figure 1B). DA chemotherapy was the most common IC overall (48%), followed by FLAG-Ida (23%) and other ICs (18%). However, CPX-351 uptake started in 2018 (5% of all IC) and by the end of 2019 had displaced DA chemotherapy as standard-of-care IC (40% vs 22%, respectively). Excluding patients who were alive but had not received subsequent therapy (ie, censored), most patients who received front-line azacitidine or LDAC died without receiving salvage therapy (89% and 92%, respectively). In comparison, non-censored patients who received front-line DA chemotherapy or FLAG-Ida were more likely to receive salvage treatment (52% and 34%, respectively). Key salvage treatments following DA included azacitidine alone and FLAG-based therapy. Key salvage treatments following front-line CPX-351 included FLAG-Ida or DA ± hematopoietic cell transplant and azacitidine. Conclusions: This large population-level, retrospective analysis of CAS data provides a detailed overview of the management of patients with t-AML and AML-MRC. Historically, a high proportion of these high-risk patients have received less-intensive treatment. Since 2018, CPX-351 has been rapidly adopted into the IC treatment pathway, displacing DA chemotherapy. These analyses will be repeated after the CAS database has been updated to determine the impact of COVID-19. Figure 1 Figure 1. Disclosures Legg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Muzwidzwa: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Adamson: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Wilkes: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

Reducing day 3 baseline monitoring bloodwork and ultrasound for patients undergoing timed intercourse and intrauterine insemination treatment cycles

Background In the current context of a global pandemic it is imperative for fertility clinics to consider the necessity of individual tests and eliminate those that have limited utility and may impose unnecessary risk of exposure. The purpose of this study was to implement and evaluate a multi-modal quality improvement (QI) strategy to promote resource stewardship by reducing routine day 3 (d3) bloodwork and transvaginal ultrasound (TVUS) for patients undergoing intrauterine insemination (IUI) and timed intercourse (IC) treatment cycles. Methods After literature review, clinic stakeholders at an academic fertility centre met to discuss d3 testing utility and factors contributing to d3 bloodwork/TVUS in IC/IUI treatment cycles. Consensus was reached that it was unnecessary in patients taking oral/no medications. The primary intervention changed the default setting on the electronic order set to exclude d3 testing for IC/IUI cycles with oral/no medications. Exceptions required active test selection. Protocols were updated and education sessions were held. The main outcome measure was the proportion of cycles receiving d3 bloodwork/TVUS during the 8-week post-intervention period compared with the 8-week pre-intervention period. Balancing measures included provider satisfaction, pregnancy rates, and incidence of cycle cancellation. Results A significant reduction in the proportion of cycles receiving d3 TVUS (57.2% vs 20.8%, p < 0.001) and ≥ 1 blood test (58.6% vs 22.8%, p < 0.001) was observed post-intervention. There was no significant difference in cycle cancellation or pregnancy rates pre- and post-intervention (p = 0.86). Treatment with medications, cyst history, prescribing physician, and treatment centre were associated with receiving d3 bloodwork/TVUS. 74% of providers were satisfied with the intervention. Conclusion A significant reduction in IC/IUI treatment cycles that received d3 bloodwork/TVUS was achieved without measured negative treatment impacts. During a pandemic, eliminating routine d3 bloodwork/TVUS represents a safe way to reduce monitoring appointments and exposure.

PSX-4 Behavior of goats subjected to different social isolation treatments

Social isolation can be stressful to goats when they are separated from the herd for veterinary care or prior to slaughter. This experiment was conducted to determine the behavior responses in goats during isolation with or without visual contact with conspecifics. Forty-eight uncastrated male Spanish goats (8-mo old) were randomly assigned to one of four isolation (TRT) pens (1.5 x 1.5 m) with metal grill panels: (i) open grill with no visual contact with conspecifics (IO), (ii) covered panels to prevent visual contact (IC), (iii) covered panels with a 30 cm x 30 cm window on one side to allow visual contact with conspecifics (IW), or (iv) open grill to allow visual contact with conspecifics (IV, control), for 90 min (n = 12 goats/TRT). Behaviors were recorded by four trained individuals. Frequency of vocalization was recorded continuously, and moving, standing, climbing, lying, and visual contact behaviors, in addition to spatial location, were recorded at 5-min intervals, but grouped into 30-min blocks (TIME). The data were analyzed using Friedman’s Two-Way ANOVA by Ranks Test in SAS; however, unranked data means are presented. Both TRT and TIME had significant effects (P &lt; 0.01) on frequency of vocalization, with mean values of 44.1, 16.6, 4.3, and 2.1 (SEM = 4.58), respectively in IO, IC, IW, and IV groups. Vocalization was highest during the first 30-min period and decreased over time with mean frequencies of 26.9, 12.4, and 11.4 (SEM = 2.43), respectively during 30, 60, and 90 min. Frequencies of climbing and lying behaviors were the highest (P &lt; 0.01) in the IC treatment. Goats in IC group also spent more time facing the corner of the pen. The results indicate that goats with no visual contact with conspecifics spend more time vocalizing or trying to escape the pen, which may indicate distress.

Ethical Advice for an Intensive Care Triage Protocol in the COVID-19 Pandemic: Lessons Learned from The Netherlands

At the height of the COVID-19 crisis in the Netherlands a shortness of intensive care beds was looming. Dutch professional medical organizations asked a group of ethicists for assistance in drafting guidelines and criteria for selection of patients for intensive care (IC) treatment in case of absolute scarcity, when medical selection criteria would no longer suffice. This article describes the Dutch context, the process of drafting the advice and reflects on the role of ethicists and lessons learned. We argue that timely interaction between clinical and ethical expertise is necessary since the distinction between medical and non-medical considerations is not as clearcut as sometimes assumed. Furthermore, pragmatic considerations related to the specifics of an epidemic are of importance, for example, in relation to prioritizing health care workers. As a consequence, any protocol already present before the pandemic would need alterations to fit the current situation. The ‘fair innings’ criterion we proposed, rephrased as an argument of intergenerational solidarity, was considered reasonable by professionals as well as patient organizations. While it is desirable to draft ethical guidelines in ‘peacetime’ as a matter of pandemic preparedness, the pressure of an actual crisis facilitates decision-making, although it will also complicate a more democratic approach.

2108. Comparison of Voriconazole vs. Itraconazole in the Treatment of Histoplasmosis – A Retrospective Analysis

Background The guideline-preferred azole for histoplasmosis (HP) is itraconazole (IC). While voriconazole (VC) has shown success in in-vitro and in retrospective analyses, there has not been enough data to include newer generation azoles as first-line treatment for infections with Histoplasma capsulatum. Methods We conducted a single-center retrospective cohort study of adult patients diagnosed with HP from 2002 through 2017. Data included demographics, clinical features and sites of infection, immune status, treatments, and mortality. Patients were categorized into two groups based on initial choice of azole (IC or VC) and mortality was compared between these two groups. The treatment groups were defined based on the first azole received, either IC or VC, as initial or as step-down therapy from amphotericin. Patients initiated on other azoles were excluded. Results We identified 263 cases of HP from 2002 to 2017. After excluding patients initiated on other azoles, 194 patients remained. 175 (90%) patients were started on IC and 19 (10%) were started on VC, either as stepdown or initial choice of antifungal. There were no significant demographic differences between patients receiving IC compared with VC as their initial azole treatment. Patients with hematologic malignancies tended to be prescribed VC more frequently but this was not statistically significant (OR 3.1 [0.77–12.4]). Death occurred in 40 (23%) patients from the IC and 5 (26%) patients from the VC group. The hazard ratio for mortality with the use of VC was 1.21 (CI 0.4–3.6, P = 0.73). Conclusion IC is the mainstay in the treatment for HP. It appears that VC has comparable outcomes to IC and can be considered an alternative treatment option for HP, at least for patients with contraindications to IC treatment. Disclosures All authors: No reported disclosures.

Assessment of Intercropping and Plastic Mulch as Tools to Manage Heat Stress, Productivity and Quality of Jalapeño Pepper

Under a global warming scenario, it is important to adopt practices that favor soil water conservation, such as plant intercropping systems and the use of plastic mulching. The objective of this study was to determine how microenvironment, morphology, productivity and quality of jalapeño peppers were affected by corn intercropping and the use of plastic mulching. Two experiments were conducted during 2015 and 2016 in the Valley of Mexicali, Mexico, a region characterized by its extreme aridity, soil salinity, hot temperatures and high radiation during the summer. Four treatments were tested: jalapeño peppers grown on bare soil (BS); on bare soil intercropped with corn (BS+IC); on plastic mulch (PMu); and on plastic mulch intercropped with corn (PMu+IC). The response variables measured were yield, fruit quality attributes, microclimatic variables, and morphology of the pepper crop. PMu treatment produced the tallest pepper plants and yields, while the BS+IC treatment produced the smallest plants and the lowest yields. A possible explanation for the higher biomass and crop yield of the PMu treatment is the lack of competition from corn and the effect of plastic mulching in reducing soil salinity. It is concluded that competition from corn on jalapeño pepper dramatically affected the pepper’s productivity, particularly under high soil salinity and extremely high temperature conditions.

Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).

204 Background: In the phase 3 MPACT study, treatment with nab-P + G resulted in a > 3-fold reduction in primary pancreatic tumor burden vs G in patients with metastatic PC, suggesting the potential for activity against LAPC. This international, multicenter single arm, phase 2 trial (LAPACT) was designed to evaluate the efficacy and safety of an induction phase regimen of nab-P + G in previously untreated patients with LAPC. Methods: Treatment-naive patients with unresectable LAPC and Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 were enrolled. The induction phase was designed as 6 cycles of nab-P 125 mg/m2 + G 1000 mg/m2 on D 1, 8, and 15 of each 28-day cycle. After induction, patients without progressive disease or unacceptable adverse events were eligible for continued treatment with nab-P + G, chemoradiation, or surgery per investigator’s choice (IC). Surgery could occur prior to completing 6 induction cycles if the investigator deemed there had been a sufficient tumor response. The primary endpoint was time to treatment failure (TTF) in patients treated with nab-P + G as induction therapy followed by IC treatment. Key secondary endpoints included disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 107 patients enrolled, 106 were evaluable for the safety analysis. No new toxicities were identified. The most common grade ≥ 3 treatment-emergent adverse events during induction were neutropenia (42%), anemia (11%), and fatigue (10%); grade 3 peripheral neuropathy occurred in 4% of patients. The most frequent reasons for discontinuing induction were adverse events (18%) and progressive disease (7%). Forty-six (43%) patients received IC treatment after induction: 13 (12%) continued nab-P + G, 17 (16%) received chemoradiation, and 16 (15%) underwent surgical resection (R0, n = 7; R1, n = 9). DCR and ORR during induction were 78% and 35%, respectively; with a median TTF of 8.6 months and median PFS of 10.2 months. Conclusion: A nab-P + G induction regimen in LAPC appears tolerable and feasible and is associated with encouraging antitumor activity and promising TTF and PFS. NCT02301143. Clinical trial information: NCT02301143.

Densification treatment and properties of carbon fiber reinforced contact strip

The high temperature caused by current-carrying wear could affect the thermal reliability of resin-based contact strip greatly. This study adopted liquid-phase impregnation-carbonization (IC) technique to improve the thermal stability and densification of carbon fiber reinforced contact strip (CFRCS). The influence of this method was investigated by scanning electron microscopy, Fourier transform infrared spectrometry, thermal gravimetric analysis and energy-dispersive spectrometry; meanwhile, specimen composition and friction and mechanism properties were also analyzed. The results show that heat treatment is helpful in improving the material’s temperature tolerance. When specimens undergo IC treatment four times, resistivity and wear rate would reduce gradually under impregnating conditions of carbonization temperature (800°C), dipping liquid concentration (60%), and dipping temperature (60°C). IC treatment is effective in reducing material porosity and improving the impact resistance performance compared with only carbonized sample. Densification treatment can also improve the samples’ compressive strength and bending strength. The main wear mechanisms of CFRCS-25 and CFRCS-800 against copper with electrical current are similar; these are arc erosion wear and oxidation wear accompanied by adhesive wear. Adhesive wear and oxidative wear is more severe for CFRCS-25 than CFRCS-800.

CHANGES IN BRONCHIAL ASTHMA CONTROL AND INFLAMMATION BIOMARKERS DURING THE ALLERGEN-SPECIFIC IMMUNOTHERAPY AND ACCOMPANYINGTREATMENT

Background. The work is devoted to the studying of the correspondence between the symptoms dynamics and the concentrations of the nitrogen oxide (NO) methabolites in the exhaled breath air condensate in patients with bronchial asthma (BA) during allergenospecific immunotherapy (ASIT) and accompanying treatment. Methods. The symptoms of BA were estimated using the Asthma Control Questionaire (ACQ). The inflammation biomarkers level (NO methabolites in the exhaled air condensate) was measured by the spectrofluorometric method of Griess. Results. During ASIT and accompanying treatment (cetirizine or levocetirizine with basis BA therapy corresponding to the observed BA severity with allergens eliminated), the symptoms reduction (decrease in the total ACQ scores) was observed along with decrease of the total concentration of NO metabolites in blood. This was observed both for the steroid- naive patients and for the patients taking the inhaled corticosteroids (IC) treatment. Conclusion: In patients with mild BA, combination of ASIT and non-steroid accompanying therapy on the basis of cetirizine or levocetirizine results in the improvement of the BA control and reduction of the allergic inflammation in airways comaparable to the analogous processes in patients with moderate BA taking the analogous therapy but with IC included.