World Experience Research Articles

THE NEED TO INTRODUCE GREEN AND CARBON TAXES IN RA

Currently, environmental problems that arise in most countries of the world require the transition of certain sectors of the economy, economic entities to the creation of the best and affordable technologies by means of tax regulation. Environmental taxes and fees contribute to the modernization of production, the development of competitiveness, the reduction of energy-intensive production, the development of modern scientific research. In the article, the world experience of applying economic mechanisms for regulating the protection and use of the environment is analyzed, the directions of the state policy implemented in Armenia are discussed and reviewed, conclusions and proposals for tax regulation are made.

Analysis of the world experience on the approaches to the definition of disability: on the way to reforming the system of medical and social expertise

The Ukrainian system of medical and social expertise needs to revise its conceptual and methodological foundations in accordance with the realities of the current development of social sciences in the world and demand of the state regarding the modern understanding of disability. The purpose of the study was to analyze international experience and legislation on policy towards persons with disabilities and systematic approaches to the criteria of violation of functioning and the possibilities of determining the status of "person with disabilities" using the basic principles of the International Classification of Functioning (ICF), Impairment and Health to create optimal approaches to determining the criteria for disability in Ukraine. The study was based on the analysis of available scientific literature and legislative documents of developed countries on the understanding of the concept of "person with a disability". The scientometric databases used were Scopus, Web of Science, Google Scholar, and MedLine. Data from the official websites of the Political Department of the European Parliament, WHO, the United Nations, UNICEF, the World Bank. According to the results of the study, it is determined that a single state body is responsible for determining the status of a person with a disability in sustainable development countries using a multidisciplinary approach. The author identifies 3 main components that most developed countries assess when determining disability: economic, medical and social. At the same time, the main criterion is decreased performance. It has been established that since 2022, Spain has completely switched to the criteria of the International Classification of Functioning in determining the signs of disability, basing the severity of a person's condition as a degree of disability on a percentage decrease in the person's functioning. Some European countries use selective categories of the ICF.

BASIC PRINCIPLES OF PARK ZONES ARRANGEMENT IN THE CONDITIONS OF THE MODERN CITY

The main principles of park zones arranging in the conditions of modern cities are analyzed in order to determine the optimal approaches to their development and organization, in particular, taking into account ecological, socio-economic and aesthetic aspects. Arguments are given that speak of the importance of observing the rules of zoning of such territories and prove the impact of the presence of properly located park zones on the physical and mental health of people. The most effective strategies for preserving the natural environment and creating a comfortable space for the city's residents have been determined, as well as potential obstacles and problems that may arise in the process of setting up park areas, and suggestions for overcoming them have been identified. The article provides a comparative analysis of the arrangement of park zones in Mariupol and Berlin. Fundamental differences in the planning of park zones as recreation areas for city dwellers have been identified. Innovative methods of using space, the introduction of eco-friendly materials and technologies, as well as the interaction of park zones with other aspects of urban planning (residential districts, the business part of the city, industrial zone, etc.) to create a healthier, sustainable and attractive urban environment were studied. The studies were carried out in accordance with the current regulatory documents, which regulate the basic principles of arranging park zones, taking into account world experience regarding location, planning, filling (small architectural forms, monuments, lighting, landscaping) and other aspects. The main criteria for the optimization of park zones are: preservation of the existing priority direction of territory use while increasing the protection regime of individual areas; preservation of green areas and historical integrity of the territory; preservation and restoration of the formed landscape and architectural features of parks-monuments of garden and park art; appropriate territorial ratio of functional zones, organization of care for park territories at the level of local authorities and compliance with rules of use. Arrangements of park and green areas of cities from different countries were compared. Keywords: park areas, modern trends, green areas.

Edukasi Dan Simulasi Senam Tera Untuk Pencegahan Hipertensi Pada Lansia Di Desa Nguri Kecamatan Lembeyan Kabupaten Magetan

As a person ages, various changes often arise due to a decrease in biological function caused by the aging process. Hypertension is one of the NCDs that is a threat, especially to the elderly. Based on data from the World Health Organization (WHO) in 2019, it shows that around 1.13 million people in the world experience hypertension. Nguri Village is one of the villages in Lembeyan District, Magetan Regency, East Java Province. The problem from the results of the study in Nguri Village is that there are still many people, especially the elderly, who suffer from hypertension and a lack of understanding in preventing hypertension, namely 75% or 45 out of 60 elderly people. The aim of community service is to increase knowledge regarding efforts to prevent hypertension. The implementation method uses health education in the form of doing tera exercises to prevent hypertension in the elderly. Previously, blood pressure was measured. Activities were carried out on 30 hypertensive elderly aged >40 years. The results of the activity were that the elderly knew about preventing hypertension, namely 95% of the 30 elderly were able to understand and the elderly were able to carry out tera and exercise activities. The elderly play a very active role in this activity.

Left ventricular ejection fraction by computed tomography in severe aortic stenosis patients - real world experience

Left ventricular ejection fraction by computed tomography in severe aortic stenosis patients - real world experience

A Poetics of Chaos: Spatial Metaphors in Leila Aboulela’s The Translator and Minaret

While contemporary culture seems to valorize unbounded mobility as the cornerstone of a transnational and borderless world, both social and individual experience continue to be dominated by the impulse for borders and restrictions. Leila Aboulela explores this discrepancy by interrogating the spatial organization of social reality both to show the prevalence of border logic and to suggest pathways for resurgence. This paper examines how the deployment of spatial tropes in Aboulela’s early novels The Translator (1999) and Minaret (2006) is aimed at demonstrating that conceptions of space as orderly and static often serve to maintain certain power configurations. At the same time, these tropes counter the discursive drive for order by tapping into the potential for resistance that inhabits these hegemonic narratives of space. I argue that by mobilizing such tropes as border-crossing, journeying, and carnivalesque chaos, the texts in question advocate a more fluid and chaotic notion of space.

Міжнародний досвід охорони мікобіоти

The article examines the issue of the protection of fungal biodiversity using world experience. In chronological order, the stages of the creation of international environmental protection organizations, the adoption of conventions of a non-political nature, the texts and appendices to these documents on the subject of species biodiversity were analyzed. Lists of species in the IUCN Red List were studied. It was revealed that since 1948, when the IUCN was established, 26 different kinds of International Conventions, documents and initiatives have been proclaimed/adopted. Among these documents, 8 did not address the issue of biodiversity conservation or touched on this issue indirectly, only indirectly, 18 conventions and initiatives directly related to the protection of biodiversity. Analyzing the texts of these documents, the questions to which they are devoted, and their appendices, we found that specific information about mushrooms, i.e. with an indication of the species or genus, is available only in two documents: the International Red List of Mushrooms (625 species) and the IUCN Red List (811 species). Mushrooms are not mentioned as objects of protection in any Convention. The information about fungi that needs to be preserved is younger, compared to this information about plants and animals. Therefore, it is necessary to further consider the species composition of mushrooms and assess the state of their populations in order to include endangered species in the Red Lists of the national and international levels.

Dalbavancin as consolidation therapy for infective endocarditis in patients with comorbidity. A real world experience.

Infective endocarditis (IE) is a potentially life-threatening infection, the incidence of which has in creased in recent decades, particularly among elderly patients with comorbidity. The primary objective of this study was to evaluate the effectiveness of dalbavancin in the consolidation therapy of IE in patients with comorbidity six months after the end of treatment (EOT). An observational and retrospective study was conducted on patients with a Charlson Comorbidity Index (CCI) ≥ 3 who were diagnosed with IE and received consolidation therapy with dalbavancin. Forty-eight patients were included, 58.3% were male, mean age of 76.2 years (IQR: 66-88), and a mean age adjusted CCI of 6.5 (IQR: 5-7.5). Definite IE was diagnosed in 77% of cases. The most frequently isolated microorganisms were Staphylococcus aureus (45.8%) followed by Enterococcus spp. (31.3%). Complications of IE were observed in 67.7% of cases, and cardiac surgery was performed in 27% of patients. The primary reason for using dalbavancin was outpatient parenteral antibiotic therapy in 85.4% of cases. The effectiveness at EOT was 93.8%. At six months, six IE-related deaths, four unrelated deaths, and two IE relapses were observed. The effectiveness was 77%. Adverse effects related to DBV were reported in 4.2% of cases, of which 2% were considered serious. Dalbavancin has proven to be an effective alternative as consolidation antibiotherapy for IE in elderly patients with comorbidity. Moreover, a very favorable safety profile with few associated adverse effects has been observed in this population.

PECULIARITIES OF TRAINING PERSONNEL RESOURCES OF THE PUBLIC HEALTH SYSTEM IN THE SPHERE OF EPIDEMIOLOGY

Aim. An analysis of educational approaches to the training of specialists in the public health system in the field of epidemiology in Ukraine and the world was carried out with the definition of the main competencies, in accordance with the best educational international practices. Conducting an analysis of educational approaches to the training of specialists in the public health system in the field of epidemiology in Ukraine and the world with the definition of core competencies, in accordance with the best educational international practices. Materials and methods. Critical narrative literature review, based on scientific works indexed in the scientometric databases Medline, Google Scholar, PubMed, with directory of open access journals (Directory of Open Access Journals (DOAJ)) and data from the global network educational (TEPHINET) was conducted. Results. The world experience of training specialists in the field of epidemiology, with the aim of strengthening the health care system, shows that efforts are being directed to the training of practically oriented specialists. The main subject areas are necessary for the modern training of epidemiologists in the field of public health: epidemiological method and biostatistics, epidemiological surveillance and biosafety, epidemiology of infectious and non-infectious diseases, communication, management and leadership, computer skills. An epidemiologist must possess basic competencies: apply epidemiological research methods, synthesis of knowledge and interpretation of data to monitor diseases, respond to outbreaks, manage public health surveillance, manage staff and resources, develop written and oral communications. There is a valid opinion that competences in the field of epidemiology should be standardized, which would make the epidemiologist universal in different countries aimed at formation qualified and experienced epidemiologists who can detect, investigate and control disease outbreaks; conduct observations; analyze epidemiological data; measure the impact of interventions; and conduct applied epidemiological studies. Conclusions. The practical orientation of educational programs should provide a strong component for creating a sustainable capacity to respond to emergency situations in the field of health care at the national, regional and global levels. The Ukrainian approach to the training of epidemiologists requires changes using programs that combine theoretical learning with the predominant experience of practical work, taking into account the basic competencies with elements of mentoring and peer training, should meet modern standards of andragogy and approaches to motivating future specialists to learn throughout their lives.

Patents in metaverse: an analysis of scope and challenges

ABSTRACT ‘Metaverse’ is set to be the disruptive technology which is about to bring an overhaul in the functioning of myriad sectors ranging from education, entertainment, health care, businesses amongst others. The key feature of this technology is the immersion of physical world into a virtual world. Metaverse in a way finds its roots on the technologies of Virtual/ Augmented Reality (VR/AR) which essentially are about simulating real world and augmenting the real – world experience in the digital world. Intellectual Property Rights which exist for protection of intangible assets, hence are vital in perspective of Metaverse. This research analyses the IP form of Patents in reference to Metaverse. Patents are an attractive choice due to the commercial advantage and the higher level of protection it offers compared to other IP forms. The trend of surge in patent applications seen with emerging technologies like AI and Blockchain is likely to be reflected with metaverse. The article views the metaverse and patent domain through an overarching lens gauging the possible scope and challenges. The analysis is based on US, EU and Indian patent laws to get a comprehensive picture across the world.

Psychological Aspects of a Stable Personality in Army: World Experience

This article examines the psychological components of the formation of a full-fledged and self-sufficient personality among employees in the armed forces. As part of the consideration of the psychology of a serviceman, the world experience of military pedagogical experience in instilling moral and volitional qualities in soldiers and officers is taken as a basis. The article also describes the relevance of the topic under consideration, since the moral and psychological portrait of a modern military man is one of the main aspects of the formation of a strong and sustainable army. In addition to pedagogical and educational training, the legal aspects of the formation of military units involved in the psychological training of future soldiers are also considered.

Search for innovative solutions to improve the energy system of Ukraine: World experience

This study analyses the global experience of introducing innovations in the energy sector to identify effective solutions that can be applied to improve the energy system of Ukraine. The research methods included a comparative analysis of international experience in the energy sector, an assessment of the possibilities of adapting innovative technologies to Ukrainian conditions, and an examination of technical and economic aspects of integrating new solutions. The study analysed the experience of countries such as Germany, Denmark, the United States, Finland, the Netherlands, Sweden, Japan, China, France, and South Korea, which have succeeded in implementing innovative solutions in the energy sector, in particular, in the integration of renewable energy sources (RES), the development of smart networks, energy decentralisation, energy storage technologies, and energy efficiency improvement. It is identified that the most efficient approaches include the integrated use of renewable energy sources in combination with energy storage, which ensures the stability of energy supply even in conditions of uneven electricity production. The importance of smart networks for optimising energy distribution and reducing losses is also emphasised. The decentralisation of energy and the development of energy cooperatives contribute to improving energy security and community engagement. The study also showed that the introduction of smart energy management systems at the consumer level helps to increase the flexibility of the energy system and effectively respond to fluctuations in demand. In addition, it is determined that the successful implementation of innovative projects in the energy sector requires state support through subsidies and regulatory incentives. Based on international experience, it is concluded that combining technical solutions with effective management and political initiatives is key to ensuring the sustainable development of the Ukrainian energy system

Sentiment Analysis-Based Automatic Stress and Emotion Recognition using Weighted Fused Fusion-Based Cascaded DTCN with Attention Mechanism from EEG Signal

When loaded with difficulties in fulfilling daily requirements, a lot of people in today’s world experience an emotional pressure known as stress. Stress that lasts for a short duration of time has more advantages as they are good for mental health. But, the persistence of stress for a long duration of time may lead to serious health impacts in individuals, such as high blood pressure, cardiovascular disease, stroke and so on. Long-term stress, if unidentified and not treated, may also result in personality disorder, depression and anxiety. The initial detection of stress has become more important to prevent the health issues that arise due to stress. Detection of stress based on brain signals for analysing the emotion in humans leads to accurate detection outcomes. Using EEG-based detection systems and disease, disability and disorders can be identified from the brain by utilising the brain waves. Sentiment Analysis (SA) is helpful in identifying the emotions and mental stress in the human brain. So, a system to accurately and precisely detect depression in human based on their emotion through the utilisation of SA is of high necessity. The development of a reliable and precise Emotion and Stress Recognition (ESR) system in order to detect depression in real-time using deep learning techniques with the aid of Electroencephalography (EEG) signal-based SA is carried out in this paper. The essentials needed for performing stress and emotion detection are gathered initially from benchmark databases. Next, the pre-processing procedures, like the removal of artifacts from the gathered EEG signal, are carried out on the implemented model. The extraction of the spectral attributes is carried out from the pre- processed. The extracted spectral features are considered the first set of features. Then, with the aid of a Conditional Variational Autoencoder (CVA), the deep features are extracted from the pre-processed signals forming a second set of features. The weights are optimised using the Adaptive Egret Swarm Optimisation Algorithm (AESOA) so that the weighted fused features are obtained from these two sets of extracted features. Then, a Cascaded Deep Temporal Convolution Network with Attention Mechanism (CDTCN-AM) is used to recognise stress and emotion. The validation of the results from the developed stress and emotion recognition approach is carried out against traditional models in order to showcase the effectiveness of the suggested approach.

Surrogate Motherhood: World Experience and Practice of Legal Regulation

Surrogate Motherhood: World Experience and Practice of Legal Regulation

Absolute Lymphocyte Count and Outcomes of Multiple Myeloma Patients Treated with Idecabtagene Vicleucel: The US Myeloma Immunotherapy Consortium Real- World Experience

Idecabtagene vicleucel (ide-cel) has shown impressive efficacy in relapsed/refractory multiple myeloma (RRMM). This study aimed to investigate the impact of absolute lymphocyte count (ALC) on the survival outcomes of RRMM patients treated with standard of care (SOC) ide-cel. Data were collected retrospectively from 11 institutions in the U.S. Impact of ALC parameters including pre-apheresis (pre-A), pre-lymphodepletion (pre-LD), absolute and percent difference from pre-A to pre-LD on clinical outcomes after ide-cel were examined using survival analysis. A new ALC profile was created based on univariate analysis that comprises 3 groups: normal (≥1 × 109/L) pre-LD ALC (LDN), low (<1 × 109/L) pre-LD ALC (LDL) + percent reduction <37.5 (%RL), and LDL ALC + percent reduction ≥37.5 (%RH). A total of 214 SOC ide-cel recipients were included in this analysis. The median patient age was 64 years (interquartile range [IQR], 57 to 69 years), median number of prior therapies was 6 (IQR, 5 to 9), and median duration of follow-up was 5.4 months (IQR, 2.1 to 8.3 months). Most patients had both low pre-A ALC (75.3%) and pre-LD ALC (77.2%), and the reduction from pre-A to pre-LD (median, .65 to .55 × 109/L) was statistically significant. Univariate analysis showed that the LDL + %RH group had significantly worse progression-free survival (PFS) and overall survival (OS) compared to the LDL + %RL and LDN ALC groups (6-month PFS: 40% versus 67.6% and 60.9%; 6-month OS: 69.5% versus 87% and 94.3%). In multivariable analysis, after adjusting for age, performance status, cytogenetic risk, use of bridging therapy, and extramedullary disease, PFS did not maintain its statistical significance; however, OS remained significantly worse for LDL + %RH group compared to the LDN ALC group (hazard ratio [HR], 4.3; 95% confidence interval [CI], 1.1 to 17), but the difference between the LDL + %RH versus %RL groups was not statistically significant (HR, 1.7; 95% CI, .8 to 4.0). Our findings indicate that low pre-LD ALC with high %R from pre-A to pre-LD was associated with inferior survival outcomes, particularly OS, in patients who received SOC ide-cel.

Modern successful global solutions in environmentally friendly urban delivery and their application in Ukraine

Nowadays the issue of reducing environmental pollution is on the agenda of all countries. Among the areas that have huge negative consequences for nature, logistics and supply chains take their place. Today, there are many concepts and scientific currents that recognize the need to account for the environmental component in urban logistics. Environmental aspects are used when evaluating the efficiency of investment projects, developing new models of vehicles, calculating taxes and insurance payments, and when searching for the best delivery schemes. The goal of the work. Taking into account the world experience in research on the chosen topic, the purpose of this study is to consolidate the world's successful experience in environmentally friendly urban delivery and assess their applicability in Ukraine. Technologies and methods that allow reducing the negative impact of motor vehicles on the environment include: The technology of off-peak delivery, which allows you to improve the speed mode of the car. With off-peak delivery, the probability of traffic jams is minimized, which makes the speed of movement the maximum permissible in the city (and, accordingly, the most environmentally friendly). Although night delivery is currently not possible in Ukraine due to the curfew, late and early delivery is still available, allowing you to successfully bypass traffic jams. Use of consolidation centers. The economic idea of consolidation of freight transportation is to use the effect of scale - the greater the carrying capacity of the vehicle, the lower the specific costs for transportation of a unit of production. Currently, the construction of the consolidation center is being evaluated from the point of view of the impact of the supply chain on the environment. At the same time, the existence of a consolidation center near or within the city allows to organize delivery by vehicles with zero or low level of environmental pollution. Use of Parcel Delivery Lockers. Delivery lockers are usually installed in places where the maximum flow of residents is concentrated, which makes it possible to create additional comfort for users due to the possibility of choosing the point closest to their own home or place of work. This method eliminates up to two thirds of harmful emissions into the air. The number of post machines and the area covered by them increases year by year, which allows us to talk about the success of this technology. According to the results of 2022, such major players of express delivery as "Nova Poshta" (now “Nova”), "Ukrposhta" and "Meest" will continue to work with post delivery lockers in Ukraine. Use of more environmentally friendly types of transport. The use of hybrid, electric or non-motorized vehicles is increasingly used in last-mile logistics. Electric vehicles, mopeds, two- or three-wheeled bicycles with a large trunk or cargo body can be considered environmentally friendly types of urban logistics. Such vehicles have practically zero emissions of harmful substances, they are much more maneuverable and do not require a lot of space for unloading, loading and parking. Implementation of zones with low (zero) air pollution. Zones with zero or low emissions have long been used in developed countries. There are no generally accepted technologies for calculating the territory that requires restrictions on the movement of transport, as well as for calculating the cost of such movement. Usually it depends on the will of the local authorities, the wishes of the residents and the well-being of the region. Prohibition on the use of motor vehicles. Some local authorities introduce a complete ban on the use of motor vehicles within certain parts of the city. Usually these are historical centers with dense buildings and a large number of tourists. Sometimes such drastic measures are combined with night delivery technology. If this is not possible, the only alternative is delivery by small, usually two- or three-wheeled, zero-emission vehicles. Improvement of traffic management. Competently designed organization of road traffic can reduce the pressure on the environment. The use of an intelligent transport system in smart cities allows you to perform important tasks like detection of transport accidents; automated control of the ramp, traffic lights and parking, etc. Improvement of road conditions. This refers to the quality of the road surface, markings, cleanliness of the road surface, etc. Improvement of road conditions indirectly affects the improvement of environment of the region. Summing up the results of the research, successful global practices in environmental friendly urban logistics are highlighted, which are applied and have prospects for application in Ukraine. It was concluded that there is a huge potential of using world experience in urban logistics of Ukraine. This will bring Ukrainian logistics and urban supply chains to a new level, increasing the level of health and general satisfaction of the citizens.

PRINCIPLES, TYPES AND TASKS OF FORMING THE IMAGE OF REGIONS

This article focuses on issues aimed at forming the image of the territory of Uzbekistan, the classification and structure of the image. World experience in shaping the image of regions is studied and compared with foreign trends. Today, attention is paid to the issues of Uzbek image formation at the world level.

Treatment outcomes of the KEYNOTE-522 regimen in an ethnically diverse patient population: A real world experience.

e12663 Background: Pembrolizumab (pembro) in combination with neoadjuvant chemotherapy (NACT) became standard of care for high risk, early stage TNBC on July 26, 2021, as a result of the KEYNOTE-522 trial. Black women are disproportionately affected by TNBC with more advanced stage at diagnosis, however the KEYNOTE-522 did not collect data on race. This retrospective review evaluates response to pembro plus NACT in a racially diverse population to assess the generalizability of the trial findings to potentially under-represented patient populations. Methods: This is a single center, retrospective review of patients with stage II/III TNBC diagnosed between 08/2020 to 08/2023, treated with pembro plus NACT at Maimonides Medical Center, a safety-net hospital in Brooklyn, New York serving a diverse patient population. Exclusion criteria included age &lt; 18 years, ER/PR/Her2 positivity, NACT without pembrolizumab and unreported race. Data were collected from electronic health records and analyzed using SPSS Statistics. Results: 50 patients met inclusion criteria, among whom 40 patients had complete information available for review. 52.5% (95% CI: 38% - 69%) of patients had a pCR. Nearly half of the patient population (47.5%) were African American. Subgroup analysis of ethnicity demonstrated a lower pCR amongst African American women, but this was not statistically significant (table). 5 patients had progression of disease with the development of distant metastasis (2 whilst on treatment and 3 following completion of therapy). 3 patients had grade 3/4 adverse events (pembro associated endocrine and cardiac dysfunction). Notably, lack of complete imaging response to treatment was significantly associated with lack of pCR (p=0.003). Conclusions: In this retrospective review of a racially diverse patient population, the pembrolizumab-NACT regimen was well tolerated with an acceptable side effect profile. While our rate of pCR is lower than the findings of the Keynote-522 trial; 52.5 % (95% CI: 38% - 69%) vs. 64.8% (95% CI: 59.9%-69.5%), our sample size is not large enough to detect a statistically significant difference. Sub-analysis of patient ethnicity demonstrated varying rates of pCR, however findings are limited by a small sample size. Additional data collection is in progress and future analysis will provide insight into a potential correlation between race and therapy response. [Table: see text]

Outcomes in patients (pts) with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) treated with systemic therapy from real world experience (ORCHID) study.

e19067 Background: Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, has shown compelling efficacy (objective response rate [ORR] 52%, complete response [CR] rate 31.5%) and a generally manageable safety profile in pts with heavily pretreated R/R DLBCL in the single-arm ELM-2 trial (NCT03888105; Ayyappan et al. ASH 2023). We evaluated outcomes in pts with R/R DLBCL treated with currently available third-line or later (3L+) therapies in a real-world setting (ORCHID; NCT05338892) to better evaluate results from ELM-2 in the absence of a randomized control arm. Methods: ORCHID is a multicenter, retrospective, observational study, using electronic medical record or research databases, of pts with R/R DLBCL who have received ≥2 prior lines of therapy (LoTs; including an anti-CD20 and an alkylator) and initiated 3L+ systemic therapy for DLBCL between January 1, 2015 and June 30, 2021. After applying similar eligibility criteria to those in the ELM-2 trial, inverse-probability of treatment weighting (IPTW) was used to balance key prognostic variables between the trial and real-world cohorts. Pts were followed from the start of qualifying LoT until death, end of study period (December 31, 2021), or loss to follow up, whichever occurred first. The primary endpoint was ORR per Lugano criteria assessed by independent central review (ICR). Secondary endpoints included ICR-assessed CR rate, disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS) (see Thieblemont et al. ASH 2022). Results: Pts in ORCHID (N=148) generally had less severe disease than trial pts prior to IPTW. The most commonly used regimens were anti-CD20 based therapies, CAR T, and chemotherapy alone. The IPTW cohort had a median age 65 y, 79% Ann Arbor stage III/IV, 66% primary refractory, 88% refractory to last LoT, and median (range) prior LoT: 2 (2–6). In the IPTW cohort, ORR was 44%, CR 18%, and DCR 50%. Median (m) PFS (mPFS), DOR (mDOR), and OS (mOS) were 7.2, 9.0, and 10.8 mo, respectively. Given the lack of regular scans in routine practice (47% of pts had only one ICR response assessment over the study period), sensitivity analysis that considered subsequent treatment as progression resulted in shorter mPFS (4.6 mo) and mDOR (6.1 mo). In the majority of LoTs initiating non-CAR T therapy (n=111), ORR was 33%, CR 15%, DCR 43%. The mOS in non-CAR T group was 7.5 mo and was not reached in those intended for CAR T. Conclusions: Pts in the ORCHID study, especially those who did not receive CAR Ts, had markedly lower response rates than those in the R/R DLBCL cohort of ELM-2. Despite prior failure, most pts still received an anti-CD20 based regimen in 3L+ setting in routine practice, highlighting the need for treatment options with different mechanisms of action that provide deep and durable responses and improve outcomes in this pt population. Clinical trial information: NCT05338892 .

Real world experience of bispecific fusion protein in patients with metastatic uveal melanoma: Can we deliver?

e21504 Background: Effective treatments for patients with metastatic uveal melanoma has remained a longstanding unmet need. Poor response rates to checkpoint inhibitors has increased the need for patients to access new ways of targeting this disease. Tebentafusp is a first in class T Cell receptor bispecific fusion protein that has demonstrated an overall survival benefit. However although licensed it has yet to be approved in the UK for wider use. Methods: Prospective data collection on five patients receiving tebentafusp through the Managed Access Programme at a cancer centre that had not taken part in any trials of this therapy before. Patients were permitted with metastatic uveal melanoma; ECOG performance status 0-1 and were HLA-A*02:01 positive. Protocols were disseminated across the wider cancer teams for the management of side effects including cytokine release syndrome. Patients received extended monitoring for at least 16 hours, and vital signs (blood pressure, heart rate, temperature and pulse oximetry) taken every 2-4 hours. Drop in systolic BP &lt; 20mmHg treated with IV fluids. Results: Five patients with advanced uveal melanoma participated in the Access Programme at one cancer site to assess efficacy, tolerability and workforce upskilling and capability with a first in class bispecific fusion protein therapy. All patients were HLA-A*02:01 positive. The patients commenced therapy between November 2021 and July 2023. All were male; median age 66. Four patients developed cytokine release syndrome commencing at cycle one. These patients required intravenous fluids for CRS grade 2, no patients required vasopressors. One patient required IV hydrocortisone. Four patients developed skin toxicity. These were managed with antihistamines and steroids. Three patients stopped due to confirmed disease progression, receiving 2-7 cycles; one made an informed decision to stop due to grade 3 skin toxicity. One patient continues on tebentafusp and has received 32 cycles to date. They recently had treatment paused for ablation and resection of oligometastatic disease that found residual uveal melanoma and have restarted. Conclusions: Real-world data suggests that using a gp100-targeting TCR/anti-CD3 bispecific fusion protein is tolerated and deliverable in new settings. Tebentafusp was delivered without any medical emergencies and CRS was successfully managed with proactive fluid management and steroids. The rate and grading of side effects reflects that described in the large randomised controlled trial. Patients with uveal melanoma can derive ongoing clinical benefit - including one patient who has received 32 cycles and proceeded to surgical resection of oligometastatic disease. Through workplace education and upskilling, the proactive management of the side effects including cytokine release syndrome can be managed in the oncology inpatients and seamlessly moved to outpatient settings.