Interim Findings Research Articles

Safety and immunogenicity of a booster dose of S-268019-b: Interim findings of a Phase 3, open-label clinical study in Japan

Despite the initial success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in prevention of symptomatic and severe diseases, booster vaccination has become increasingly important with the advent of variants with immune-escaping capacity. Herein, we report the safety and immunogenicity of S-268019-b, comprising SARS-CoV-2 spike protein and a squalene-based adjuvant, as a booster dose. We performed an interim analysis of an open-label, Phase 3 study data until Day 29 following S-268019-b booster in Japanese adults (aged 20–64 years) who had completed primary vaccination with mRNA-1273 and in Japanese elderly (aged ≥ 65 years) who had completed primary vaccination with mRNA-1273 or BNT162b2. Reactogenicity was mild in most participants; no serious treatment-related adverse events were noted. S-268019-b enhanced SARS-CoV-2 neutralizing antibodies, immunoglobulin G antibodies, and predominant T-helper 1-mediated immune reaction in all cohorts, regardless of age, in Japanese participants with prior vaccination with mRNA vaccines.

COVID-19 vaccine booster doses provide increased protection against COVID-19 hospitalization compared with previously vaccinated individuals: Interim findings from the REFORCO-Brazil real-world effectiveness study during Delta and Omicron

BackgroundAlthough COVID-19 booster vaccination is widely recommended, there is limited long-term, population-level, real-world evidence on the magnitude of improved protection against severe COVID-19 conferred by boosting with monovalent COVID-19 vaccines developed against ancestral SARS-CoV-2, especially in low- or middle-income countries. We present interim results from the first large-scale assessment of the relative vaccine effectiveness (rVE) of first and second booster doses against severe COVID-19 in a low-/middle-income country. MethodsREFORCO-Brazil is an ongoing, test-negative case-control study (NCT05697705) utilizing Brazil national severe acute respiratory syndrome (SARS) surveillance and vaccination data. In SARS hospitalizations from August 1, 2021 to July 31, 2022, we matched test-positive (via SARS-CoV-2 antigen/reverse transcription polymerase chain reaction [RT-PCR]) cases and test-negative case-controls (via RT-PCR) based on admission date, preceding vaccinations, and age. We evaluated the rVEs of four monovalent COVID-19 vaccines (AZD1222, Ad26.COV2.S, CoronaVac, and BNT162b2) as second boosters compared with any first boosters received ≥4 months previously, and as first boosters compared with primary-series vaccinations completed ≥4 months previously. ResultsThe overall rVE of second boosters, from 5668 (2238 test-positive) evaluated hospitalizations, was 24.7 % (95 % confidence interval [CI]: 12.6–35.1); the overall rVE of first boosters, from 30,272 (12,063 test-positive) hospitalizations, was 46.8 % (95 % CI: 43.3–50.0). The rVEs of AZD1222 and BNT162b2 were similar: 29.4 % (95 % CI: 8.6–45.5) and 25.5 % (95 % CI: 4.2–42.2), respectively, for second boosters; and 42.5 % (95 % CI: 28.0–54.0) and 50.8 % (95 % CI: 47.5–54.0), respectively, for first boosters. In general, rVEs were higher in elderly (≥80 years) and immunocompromised/high-risk individuals. ConclusionsOur results support the use of AZD1222 and other adenoviral/mRNA vaccine boosters to maintain protection against COVID-19 hospitalization from Omicron subvariants, including in elderly and immunocompromised individuals at increased risk of accelerated waning or severe outcomes.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial

GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n=3039) or ChAdOx1-S (n=997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit >-5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Application of a Multi-Stage Testing and Evaluation Approach for a Safety-Related Digital Upgrade at a Nuclear Power Plant

There is an imminent need for existing United States nuclear power plants to reduce their operating and maintenance costs to remain economically viable. Digital technology provides significant opportunity for the existing nuclear power plant fleet to transform that way in which work is accomplished to reduce costs and allow the fleet to remain economically competitive. However, a careful understanding of the human-technology integration is needed to ensure the continued safe and reliable operation of these existing plants with new digital capabilities. This work presents interim findings in applying human factors engineering to a safety-significant digital upgrade for a United States nuclear power plant, following the new Alternative Review Process in the recently revised Digital Instrumentation and Control Interim Staff Guidance Licensing Process, Revision 2. The interim results described in this work provides an industry perspective, based on ongoing work, to support recent work published from Vazquez, Green, and Desaulniers (2022).

1258 Audit of Environmental Costs for Bariatric Face to Face Clinics: A Single Centre Study – Interim Findings

Abstract Aim The NHS has committed to delivering a net zero national health system by 2045. Patient travel accounts for approximately 20% of carbon footprint amongst resource use within outpatient appointments. The increased acceptability of digitalized healthcare during the COVID-19 pandemic has helped in reducing this. The study aims to look at the carbon cost of in-person bariatric clinics over a two-month period. Method A prospective review of all in-person bariatric clinics in a single high-volume bariatric center was carried out from October 2022 to December 2022. Patient’s postal codes were used to estimate mileage and duration of travel to the hospital via Google Maps. The Centre for Sustainable Healthcare Patient Travel Emission Calculator was used to estimate carbon dioxide emissions of different travel modes. Calculations were adjusted for the number of people attending with the patient and mode of travel. Results Between October and December 2022, there were a total of 48 in-person bariatric clinics. Of which, 87.5% traveled by car and 4.2% by bus or taxi. The total distance traveled was 2727 km, equivalent to 58.5 hours of travelling time. The total CO2 emissions and estimated travel-related costs were 277.4 kg and £534.98. Travels by car had the highest impact on travel costs and carbon emissions, followed by taxi and bus. Conclusions Significant cost and emission reduction could be potentially achieved by remote consultation rather than in-person clinics. Data collection is ongoing with the aim of collecting information from at least 100 patients.

Separation as Policy and Experience: Interim Findings of the Hamburg Research Project on Sent-away Children

Separation as Policy and Experience: Interim Findings of the Hamburg Research Project on Sent-away Children

Understanding Measurement of postural hypotension: a nationwide survey of primary care practice in England.

Postural hypotension (PH), the drop in blood pressure (BP) on standing, is associated with falls, all-cause mortality and cognitive decline. PH diagnostic criteria require lying-to-standing BP measurements. PH Prevalence in older adults is 20%, however, it is infrequently recorded in primary care records, suggesting PH testing and/or recording is under-utilised in this setting. To understand current PH measurement and management by primary care practitioners in England. Clinical Research Networks circulated an online survey to primary care clinicians involved in measurement of BP. Demographics and responses were summarised as percentages, or median and inter-quartile ranges (IQR), as appropriate. The survey remains open until 30 November 2022; full results will be presented at the conference. To date, there are 669 replies (341 doctors, 179 nurses, 70 healthcare assistants, 23 pharmacists, 56 other roles); median age 45 (IQR 38 to 53), 72% female. Overall, 597 (89%) responders check for PH, predominantly when symptoms are present (98%). Less common reasons to check include patients being over 80 (24%), Parkinson's disease (21%), hypertension reviews (18%), medication reviews (12%) or diabetes reviews (11%). Sitting-to-standing BP measurements are common (77%); only 22% use lying-to-standing. Only 64% ensure a rest period before sitting or lying BP measurement and only 1 (IQR 1 to 2) standing BP measurement is made, usually (66%) within the first minute of standing. Interim findings suggest that most PH assessments in primary care do not meet current guideline criteria. Full findings from this survey are expected to inform and influence future national guidelines.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis

Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the first 2 parts of a 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In the placebo-controlled Part 1, a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited hemagglutination inhibition (HAI) titers against vaccine-matched strains. In the active-comparator-controlled Part 2, mRNA-1010 (25 µg, 50 µg, or 100 µg) elicited higher HAI titers than a standard dose, inactivated seasonal influenza vaccine for influenza A strains and comparable HAI titers for influenza B strains. No safety concerns were identified; solicited adverse reactions were dose-dependent and more frequent after receipt of mRNA-1010 than the active comparator. These interim data support continued development of mRNA-1010.

GRT-R910: a self-amplifying mRNA SARS-CoV-2 vaccine boosts immunity for ≥6 months in previously-vaccinated older adults

SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes. This study reports interim analyses for a phase I open-label dose-escalation trial evaluating GRT-R910 in previously vaccinated healthy older adults (NCT05148962). Primary endpoints of safety and tolerability were assessed. Most solicited local and systemic adverse events (AEs) following GRT-R910 dosing were mild to moderate and transient, and no treatment-related serious AEs were observed. The secondary endpoint of immunogenicity was assessed via IgG binding assays, neutralization assays, interferon-gamma ELISpot, and intracellular cytokine staining. Neutralizing antibody titers against ancestral Spike and variants of concern were boosted or induced by GRT-R910 and, contrasting to authorized vaccines, persisted through at least 6 months after the booster dose. GRT-R910 increased and/or broadened functional Spike-specific T cell responses and primed functional T cell responses to conserved non-Spike epitopes. This study is limited due to small sample size, and additional data from ongoing studies will be required to corroborate these interim findings.

The Effectiveness of Reactive Step Training in People with Multiple Sclerosis

Background and Purpose Falls are poorly controlled in people with Multiple Sclerosis (PwMS). Reactive stepping after a loss of balance has been associated with falls and is altered in PwMS. However, there is limited data regarding whether reactive step training improves steps in PwMS. We aimed to determine whether reactive stepping improved following two weeks of reactive step training in PwMS. Methods To date, 16 PwMS participated in an 18-week multiple baseline study. Participants attended 2 baseline assessments (B1 and B2) before training, a 2-week, 6-session training protocol, and 2 post-training assessments (P1 and P2) to assess acute (P1) and retained (P2- 8 weeks post-training) effects. Each assessment consisted of 3 backward reactive step trials. Training consisted of 32 stepping trials in the forward, backward, left, and right directions. Outcomes included the anterior-posterior margin of stability (MOS), step length, and step latency during backward stepping. Repeated measures ANOVAs were assessed training (B2 - P1; n = 16) and retention (B2 – P2; n = 8) effects. Performance change and effect sizes (η2- partial eta-squared, 0.01 small, 0.06 medium, 0.14 large) were interpreted as data collection is ongoing. Results In this interim analysis, immediately after training, participants demonstrated quicker (-45 ms, η2= 0.15) and larger steps (+2.5 cm, η2= 0.09), with a larger MOS (+3 cm, η2= 0.12) than before training. Despite only 8 participants completing the 8-week follow-up thus far, improvements in MOS (+ 3cm, η2= 0.11), step length (+7 cm, η2= 0.20), and step latency (-10 ms, η2= 0.03) were retained 2 months after training compared to B2. Discussion These interim findings suggest that reactive step training may be an effective approach to improve reactive balance in PwMS. Given the importance of reactive stepping for fall prevention, this work may impact rehabilitative care and reduce fall-risk for PwMS. Falls are poorly controlled in people with Multiple Sclerosis (PwMS). Reactive stepping after a loss of balance has been associated with falls and is altered in PwMS. However, there is limited data regarding whether reactive step training improves steps in PwMS. We aimed to determine whether reactive stepping improved following two weeks of reactive step training in PwMS. To date, 16 PwMS participated in an 18-week multiple baseline study. Participants attended 2 baseline assessments (B1 and B2) before training, a 2-week, 6-session training protocol, and 2 post-training assessments (P1 and P2) to assess acute (P1) and retained (P2- 8 weeks post-training) effects. Each assessment consisted of 3 backward reactive step trials. Training consisted of 32 stepping trials in the forward, backward, left, and right directions. Outcomes included the anterior-posterior margin of stability (MOS), step length, and step latency during backward stepping. Repeated measures ANOVAs were assessed training (B2 - P1; n = 16) and retention (B2 – P2; n = 8) effects. Performance change and effect sizes (η2- partial eta-squared, 0.01 small, 0.06 medium, 0.14 large) were interpreted as data collection is ongoing. In this interim analysis, immediately after training, participants demonstrated quicker (-45 ms, η2= 0.15) and larger steps (+2.5 cm, η2= 0.09), with a larger MOS (+3 cm, η2= 0.12) than before training. Despite only 8 participants completing the 8-week follow-up thus far, improvements in MOS (+ 3cm, η2= 0.11), step length (+7 cm, η2= 0.20), and step latency (-10 ms, η2= 0.03) were retained 2 months after training compared to B2. These interim findings suggest that reactive step training may be an effective approach to improve reactive balance in PwMS. Given the importance of reactive stepping for fall prevention, this work may impact rehabilitative care and reduce fall-risk for PwMS.

Theorising the everyday work of cycle mechanics

ABSTRACT Drawing on interim findings from an ethnography of a cycle mechanics’ workshop, this article demonstrates how the work of the mechanics rests on not only specific and contextualised craft expertise but also on distributed networks of both people and things, within which highly specialist instances of expertise or competence manifest alongside more generic, even mundane, instances of subjectivised, experiential knowledge or habit. Through an analysis of ethnographic data using a composite theoretical framework, designed as a mosaic consisting of three different but equal components, the article provides descriptions and theorisations of everyday work that reconcile contextualised situated accounts of craft expertise with the wider sociotechnological and cultural networks within which such contextualised spaces are located.

Enhancing diabetes care for the most vulnerable in the 21st century: Interim findings of the National Advisory Panel on Care Home Diabetes (NAPCHD).

Older adults with diabetes may carry a substantial health burden in Western ageing societies, occupy more than one in four beds in care homes, and are a highly vulnerable group who often require complex nursing and medical care. The global pandemic (COVID-19) had its epicentre in care homes and revealed many shortfalls in diabetes care resulting in hospital admissions and considerable mortality and comorbid illness. The purpose of this work was to develop a national Strategic Document of Diabetes Care for Care Homes which would bring about worthwhile, sustainable and effective quality diabetes care improvements, and address the shortfalls in care provided. A large diverse and multidisciplinary group of stakeholders (NAPCHD) defined 11 areas of interest where recommendations were needed and using a subgroup allocation approach were set tasks to produce a set of primary recommendations. Each subgroup was given 5 starter questions to begin their work and a format to provide responses. During the initial phase, 16 key findings were identified. Overall, after a period of 18 months, 49 primary recommendations were made, and 7 major conclusions were drawn from these. A model of community and integrated diabetes care for care home residents with diabetes was proposed, and a series of 5 'quick-wins' were created to begin implementation of some of the recommendations that would not require significant funding. The work of the NAPCHD is ongoing but we hope that this current resource will help leaders to make these required changes happen.

Feminizing care pathways: Mixed-methods study of reproductive options, decision making, pregnancy, post-natal care and parenting amongst women with kidney disease.

To identify the needs, experiences and preferences of women with kidney disease in relation to their reproductive health to inform development of shared decision-making interventions. UK-wide mixed-methods convergent design (Sep 20-Aug 21). Online questionnaire (n = 431) with validated components. Purposively sampled semi-structured interviews (n = 30). Patient and public input throughout. Kidney disease was associated with defeminization, negatively affecting current (sexual) relationships and perceptions of future life goals. There was little evidence that shared decision making was taking place. Unplanned pregnancies were common, sometimes influenced by poor care and support and complicated systems. Reasons for (not) wanting children varied. Complicated pregnancies and miscarriages were common. Women often felt that it was more important to be a "good mother" than to address their health needs, which were often unmet and unrecognized. Impacts of pregnancy on disease and options for alternates to pregnancy were not well understood. The needs and reproductive priorities of women are frequently overshadowed by their kidney disease. High-quality shared decision-making interventions need to be embedded as routine in a feminized care pathway that includes reproductive health. Research is needed in parallel to examine the effectiveness of interventions and address inequalities. We do not fully understand the expectations, needs, experiences and preferences of women with kidney disease for planning and starting a family or deciding not to have children. Women lack the knowledge, resources and opportunities to have high-quality conversations with their healthcare professionals. Decisions are highly personal and related to a number of health, social and cultural factors; individualized approaches to care are essential. Healthcare services need to be redesigned to ensure that women are able to make informed choices about pregnancy and alternative routes to becoming a parent. The original proposal for this research came from listening to the experiences of women in clinic who reported unmet needs and detailed experiences of their pregnancies (positive and negative). A patient group was involved in developing the funding application and helped to refine the objectives by sharing their experiences. Two women who are mothers living with kidney disease were co-opted as core members of the research team. We hosted an interim findings event and invited patients and wider support services (adoption, fertility, surrogacy, education and maternal chronic kidney disease clinics) from across the UK to attend. We followed the UK national standards for patient and public involvement throughout.

Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients

ObjectivesCorneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation. However, relevant disadvantages, particularly in high-risk conditions, have focused the attention on the search for alternatives. MethodsWe report interim findings of a phase I-II clinical study evaluating the safety and preliminary efficacy of a tissue-engineered corneal substitute composed of a nanostructured fibrin-agarose biocompatible scaffold combined with allogeneic corneal epithelial and stromal cells (NANOULCOR). 5 subjects (5 eyes) suffering from trophic corneal ulcers refractory to conventional treatments, who combined stromal degradation or fibrosis and limbal stem cell deficiency, were included and treated with this allogeneic anterior corneal substitute. ResultsThe implant completely covered the corneal surface, and ocular surface inflammation decreased following surgery. Only four adverse reactions were registered, and none of them were severe. No detachment, ulcer relapse nor surgical re-interventions were registered after 2 years of follow-up. No signs of graft rejection, local infection or corneal neovascularization were observed either. Efficacy was measured as a significant postoperative improvement in terms of the eye complication grading scales. Anterior segment optical coherence tomography images revealed a more homogeneous and stable ocular surface, with complete scaffold degradation occurring within 3–12 weeks after surgery. ConclusionsOur findings suggest that the surgical application of this allogeneic anterior human corneal substitute is feasible and safe, showing partial efficacy in the restoration of the corneal surface.

Carfilzomib, lenalidomide, and dexamethasone maintenance for multiple myeloma: when and for whom?

In The Lancet Oncology, Dominik Dytfeld and colleagues1 report interim findings of the ATLAS study, in which they compared carfilzomib, lenalidomide, and dexamethasone with lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma. Lenalidomide is the cornerstone of maintenance therapy2–4 and alternatives, especially for patients at high risk, have been intensively studied. However, previous trials did not randomly assign patients to lenalidomide, did not lead to licensing, and did not show superiority (even with more intensive regimens).

The impact of exercise and an increase in movement on the thoracolumbar fascia in people with lower back pain – Interim findings.

The impact of exercise and an increase in movement on the thoracolumbar fascia in people with lower back pain – Interim findings.

Numerical Simulations in Selective Catalytic Reduction Systems with an Emphasis on Injection Location

This paper is a follow-up study to previous research conducted in the field of Selective Catalytic Reduction systems. The objective of this particular study is to identify a suitable injection location for urea water solution within a chosen geometry, matching the distribution commonly used in these systems. Numerical simulations using ANSYS Fluent software were conducted, utilizing an evaporation model that had been fine-tuned based on experimental data. The droplet size injected from the nozzle was also determined from experimental data. The boundary condition applied to the walls was the “Wall-Jet” model, chosen as a compromise for time efficiency. Over one hundred simulations were conducted at more than fifty locations, with the results presented here serving as interim findings. Future research will investigate the application of the recommended injection sites in geometries similar to those used in SCR systems.

The Patient Experience with Belantamab Mafodotin: Perspectives of Patients Receiving Treatment in Clinical Trials and in the Real-World

Introduction: Belantamab mafodotin (belamaf) has been available for treatment of patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice since US approval in August 2020. Single-agent belamaf, a first-in-class B-cell maturation antigen-binding antibody-drug conjugate containing monomethyl auristatin F (MMAF) with a multimodal mechanism of action, showed deep and durable responses in the pivotal Phase II DREAMM-2 trial (NCT03525678). This study aimed to describe patients' perspectives of living with RRMM and their treatment with belamaf, based on interviews conducted in a real-world setting, supplemented by findings from interviews embedded into the DREAMM-2 trial. Methods: Semi-structured interviews were conducted with adults with RRMM receiving belamaf in real-world clinical practice and those enrolled in the DREAMM-2 trial. Real-world interviews were conducted with eligible patients who had received commercially supplied belamaf in routine care, per label, for ≥3 months prior to recruitment or had discontinued treatment within the past year and had received treatment for ≥3 months. Eligible patients for the real-world study were identified by SparkCures, a patient engagement partner that works closely with patients to help identify and explore potential clinical trial options. In the real-world study, interviews were conducted at a single time-point with patients describing how their MM and treatment-related symptoms had changed over time since starting belamaf; patients recalled bothersomeness of symptoms before starting belamaf, "at symptom worst" and "at time of interview". In DREAMM-2, patients were interviewed at Cycle 4 (C4; 2.5 and 3.4 mg/kg Q3W) and at the end of treatment (EOT); at the EOT interview, patients recalled severity of symptoms "at symptom worst" and "at time of interview". Bothersomeness (real-world study) and severity (DREAMM-2) were rated using a numeric rating scale (0=no bother/not severe; 10=extremely bothersome/severe). The DREAMM-2 trial-embedded study included all eligible patients who agreed to participate in interviews. Patients' experiences with belamaf were also qualitatively explored. Real-world study interviews are ongoing; interim findings are reported. Results: Patients who participated in real-world interviews (n=7; male 4 of 7; median 65 years; median 11 months of belamaf treatment) and patients enrolled in DREAMM-2 who participated in EOT interviews (n=38; male 20 of 38 patients; median 63.5 years) were included. Fatigue was the most frequently reported ongoing RRMM symptom in both studies (real-world: 6 of 7 patients; DREAMM-2 EOT: 22 of 38 patients). Within respective studies, mean bothersomeness/severity of most ongoing symptoms was substantially reduced "at time of interview" compared with "at worst" (Table 1). The type of ocular symptoms reported in both studies were similar and included sensitivity to light, blurred vision, and poor vision. Within respective studies, the bothersomeness/severity of patients' ocular symptoms was generally rated lower "at time of interview" compared with "at worst" occurrence (Table 2). To alleviate ocular symptoms, patients in both studies reported applying eye drops and wearing sunglasses. In the real-world study, 6 of 7 patients indicated that the benefits of belamaf treatment outweighed the treatment-related ocular changes, while 5 of 7 patients reported a preference for belamaf over past treatments. In DREAMM-2, 27 patients made ≥1 positive statement about belamaf treatment. Conclusions: These qualitative interviews provide insights into the burden of disease-related symptoms experienced by patients with RRMM treated with belamaf. Insights from DREAMM-2 support the interim real-world findings that ongoing symptoms become less bothersome/severe over time with belamaf treatment. In both settings, patients described the benefits of belamaf and their positive opinion of its efficacy/safety profile. These findings suggest patients find belamaf an important treatment option for RRMM. Funding: GSK 214290 and GSK 205678; drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Interim PET-Guided ABVD or ABVD/Escalated BEACOPP for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma (JCOG1305, INNOVATE-HL study)

Introduction Interim positron-emission tomography (PET) can predict clinical outcomes in patients with classic Hodgkin lymphoma (cHL). The objective of this single-arm confirmatory study (JCOG1305, INNOVATE-HL) is to establish interim PET-guided treatment strategy for newly diagnosed advanced-stage cHL. Methods Patients aged 16-60 years with cHL received 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as an induction chemotherapy, and then underwent an interim PET scan. Images were centrally reviewed with the use of a 5-point scale for PET findings for further response guided treatments. Patients with negative interim PET findings (defined as score 1 to 3) continued additional 4 cycles of ABVD, whereas those with positive interim PET findings (score 4 or 5) switched to 6 cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone). Involved site radiation therapy (ISRT) was set as a protocol treatment if patients with partial response had a single residual lesion after completion of chemotherapy. The primary endpoint were 2-year progression-free survival (PFS) among all eligible patients and among interim PET-positive patients (co-primary endpoints). We had the following hypotheses: 2-year PFS of eligible patients and interim-PET positive patients will exceed 75% and 35%, respectively, compared to a historical control with one-sided alpha of 0.1. Secondary endpoints included overall survival (OS), event-free survival (EFS), in which events were defined as death, progression or not achieving complete response at end of protocol treatment, and incidences of adverse events and secondary malignancy. This study was registered at jRCTs031180218. Results A total of 93 patients were enrolled from 35 institutions between January 2016 and December 2019. One patient was ineligible because of diagnostic error. Baseline characteristics of 92 eligible patients who underwent an interim PET scan were as follows: a median age of 35 years (interquartile range [IQR]: 28-48); 58% were male; most of patients (87 [95%]) had performance status of 0 or 1; Ann Arbor stage III and IV consisted of 40 (43%) and 43 (47%), respectively, the remaining 9 (10%) had stage IIB with bulky (10 cm or more) mediastinal lesion or nodal lesion involving directly to extranodal lesion; 51 (55%) and 15(16%) had B symptoms and bulky lesions, respectively. An interim PET scan showed 19 patients (21%) with positive findings; those patients received escalated BEACOPP; 18 completed 6 cycles of BEACOPP including one who underwent ISRT, the remaining one discontinued BEACOPP. On the other hand, 73 patients (79%) who had interim PET-negative findings continued ABVD; 70 completed additional 4 cycles of ABVD including two who underwent ISRT, the remaining 3 discontinued ABVD. Average relative dose intensity of induction ABVD, additional ABVD and escalated BEACOPP were 98.6% (±4.0), 96.7% (±5.7) and 82.2% (±9.3%), respectively. With a median follow-up of 41.1 months (IQR: 29.7-53.1), the 2-year PFS were 84.8% (80% confidence interval [CI]: 79.2-88.9) and 84.2% (80% CI: 69.7-92.1) among all 92 eligible patients and 19 interim PET-positive patients, respectively (Figure 1). The 2-year EFS were 76.1% and 68.4% among all eligible patients and interim-PET positive patients, respectively. Bleomycin lung toxicity (BLT) occurred in 9 patients, but no patients led to BLT-related death. Twelve and three patients underwent autologous and allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage treatment, respectively, including one received allogeneic HSCT for relapse after autologous HSCT. The 2-year OS was 98.9%; two patients died due to interstitial pneumonia after autologous HSCT and brain hemorrhage without relapsing cHL among the interim PET-positive patients, whereas no patients died among interim PET-negative patients. Diffuse large B-cell lymphoma developed in one patient with interim PET-negative findings as a secondary malignancy 4.6 years after enrollment. Conclusions This INNOVATE-HL study demonstrated that interim PET-guided treatment strategy was useful for younger patients with newly diagnosed advanced-stage cHL. Of note, 6 cycles of escalated BEACOPP is a feasible and effective regimen for interim PET-positive cHL patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal