Background In endometrial cancer (EC), preoperative anaemia, thrombocytosis and leucocytosis appear to be associated with worse prognosis. It remains unclear whether these parameters solely reflect tumour aggressiveness, or also impact response to adjuvant treatment. Therefore, our primary aim is to evaluate the prognostic relevance of anaemia, thrombocytosis and leucocytosis on survival in EC. Secondary, to explore their predictive relevance in response to radiotherapy in EC. Methods A retrospective multicentre cohort study was performed within 10 hospitals. Preoperative haematological parameters were defined as: Anaemia – haemoglobin <7.45 mmol/L (<12 g/Dl), thrombocytosis – platelets >400 × 109 platelets/L, leucocytosis – leukocytes >10 × 109/L. The relationship of haematological parameters with clinicopathological characteristics, ESGO/ESTRO/ESP risk groups and survival were evaluated. Furthermore, the predictive value of haematological parameters was determined on the overall response to adjuvant radiotherapy and for the ESGO/ESTRO/ESP intermediate-risk group solely receiving radiotherapy. Results A total of 894 patients were included with a median follow-up of 4.5 years. Anaemia was present in 103 (11.5%), thrombocytosis in 79 (8.8%) and leucocytosis in 114 (12.7%) patients. The presence of anaemia or thrombocytosis was significantly associated with ESGO/ESTRO/ESP high-risk (respectively, P = 0.002 and P = 0.041). In the entire cohort, anaemia remained independently associated with decreased disease-specific survival (HR 2.31, 95% CI (1.19–4.50), P = 0.013) after adjusting for age, the abnormal haematological parameters and ESGO/ESTRO/ESP risk groups. In patients that were treated with adjuvant radiotherapy (n = 239), anaemia was associated with significant reduced 5-year disease-specific and recurrence-free survival (P = 0.005 and P = 0.025, respectively). In ESGO/ESTRO/ESP intermediate risk patients that received solely vaginal brachytherapy (n = 74), anaemia was associated with reduced disease-specific survival (P = 0.041). Conclusions Current data demonstrate the importance of preoperative anaemia as independent prognostic factor in patients with EC. Moreover, anaemia seems to be associated with reduced response to radiotherapy. Prospective validation in a larger study cohort is needed to verify anaemia as predictive biomarker for radiotherapy. What is already known on this subject? In endometrial cancer, preoperative abnormal haematological parameters like, anaemia, thrombocytosis and leucocytosis appears to be associated with FIGO advanced-stage and unfavourable outcome. What do the results of this study add? It remains unclear whether anaemia, thrombocytosis or leucocytosis solely reflecting worse prognosis by advanced tumour stage, or also impact response to adjuvant treatment. Current data demonstrate that anaemia is independent associated with decreased disease-specific survival and anaemia seems related with reduced response to radiotherapy and in specific to vaginal brachytherapy in ESGO/ESTRO/ESP intermediate risk patients. What are the implications of these findings for clinical practice and/or further research? Specific applied adjuvant treatment is needed if patients with anaemia have a reduced response to radiotherapy in EC. Prospective validation in a larger study cohort is required to verify anaemia as predictive biomarker for radiotherapy and to further evaluate the prognostic/predictive impact of anaemia in addition to the molecular subgroups.

During the last two decades, an epidemic of a severe form of chronic kidney disease (CKD) unrelated to traditional risk factors (diabetes and hypertension) has been recognized in low- to middle-income countries. CKD of unknown aetiology (CKDu) mainly affects young working-age adults, and has become as an important and devastating public health issue. CKDu is a multifactorial disease with associated genetic and environmental risk factors. This review summarizes the current epidemiological evidence on the burden of CKDu and its probable environmental risk factors contributing to CKD in Africa. PubMed/Medline and the African Journals Online databases were searched to identify relevant population-based studies published in the last two decades. In the general population, the burden of CKD attributable to CKDu varied from 19.4% to 79%. Epidemiologic studies have established that environmental factors, including genetics, infectious agents, rural residence, low socioeconomic status, malnutrition, agricultural practise and exposure to agrochemicals, heavy metals, use of traditional herbs, and contaminated water sources or food contribute to the burden of CKD in the region. There is a great need for epidemiological studies exploring the true burden of CKDu and unique geographical distribution, and the role of environmental factors in the development of CKD/CKDu.

AbstractCausal loop diagrams (CLDs) are often used to provide an overview of important systemic elements related to an issue, rather than to inform empirical evaluations (studies which assess changes following an intervention using observed data). We suggest that empirical evaluations may benefit from the development of systems‐informed research propositions (specific testable causal assumptions with an emphasis on feedback loops) used to guide subsequent data collection, hypothesis testing and interpretation. We describe a qualitative systems‐thinking informed approach building on preexisting CLDs, published evidence, and expert/stakeholder consultation and reflect on our experience applying this to the early stages of two nature‐based solution (NBS) evaluations. We reflect on our experience and suggest that CLDs can be usefully employed to develop systems‐informed research propositions to inform subsequent empirical evaluation. This may lead to novel policy‐relevant research propositions which differ substantially from effectiveness‐oriented (“did it work?”) research questions. © 2023 The Authors. System Dynamics Review published by John Wiley &amp; Sons Ltd on behalf of System Dynamics Society.

ObjectivesChronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. MethodsRecent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings ‘HIVE’, ‘SD’, and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. ResultsDepletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. ConclusionMultiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.

People with intellectual disabilities (ID) die on an average 20years earlier to the general population. They have higher rates of multimorbidity and polypharmacy. Around 25% of people with ID report chronic constipation. The England Learning Disabilities Mortality Review found that nearly 25% of deaths identified constipation as a long-term health problem. However, the likely risk factors for constipation related harm are poorly enumerated. We sought to identify possible specific high-risk factors by examining the clinical characteristics of people with ID admitted to hospital with constipation. Data of people with ID admitted with constipation in two general hospitals covering a population of 1.3 million from 2017 to 2022 were reported using the STROBE guideline for cohort studies. Collected data included age, gender, intellectual disability severity, recorded medication, presenting complaint and co-morbidities. The medication anticholinergic burden was calculated using the anticholinergic burden scale. Continuous variables were summarised by mean and standard deviation if normally distributed, with categorical variables summarised by the number and percentage in each category. Of 46 admissions (males 52%), 57% had moderate to profound ID, 37% had epilepsy, 41% prescribed antiseizure medication (ASM) and 45% were on laxatives. Average age was 46years. The anticholinergic burden score mean was 2.3 and median, one. We can hypothesise that people with more severe ID, suffering from epilepsy and on ASM may be more at risk of developing severe constipation. Some admissions may be avoided with earlier use of laxatives in the community.

Background: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is absent or expressed at low levels in normal adult tissues but overexpressed in a range of malignancies including CLL and MCL. NVG-111 is a humanized first in class, tandem scFv, ROR1xCD3 bispecific T cell engager. NVG-111 mediates potent killing of ROR1 + tumors by engaging a unique epitope on the Frizzled domain of ROR1 and redirecting T cell activity via the CD3 binder engineered for attenuated cytokine release. Methods: In this phase 1, first-in-human, dose-escalation study (ClinicalTrials.gov identifier: NCT04763083), NVG-111 was evaluated in relapsed/refractory CLL and MCL subjects with an ECOG PS of 0-2 who received ≥2 prior lines of treatment including a Bruton tyrosine kinase inhibitor (BTKi). Bayesian continual reassessment method with overdose control was implemented to guide escalation over a dose range of 0.3-45ug/day. Each subject received at least one dose of NVG-111, administered as a continuous intravenous infusion (cIV) over 21 days followed by 7 days off drug (=1 cycle). NVG-111 was administered in combination (N=8) with ibrutinib to subjects who had achieved a partial response to &amp;gt;1 year of ibrutinib therapy, or as monotherapy in subjects that progressed after covalent BTKi/B-cell lymphoma 2 inhibitor (BCL2i) (N=4). Primary objective was safety, with the secondary objectives being efficacy (overall response rates [ORR], minimal residual disease (MRD) measured by ERIC-compliant flow cytometry and duration of response [DoR]). Serum cytokine levels were determined using a human high sensitivity cytokine premixed magnetic Luminex assay and T cell function was longitudinally evaluated using cytometry by time of flight (CyTOF) analysis. Results: Between May 2021 and July 2023 12 subjects (10 males and 2 females, median age 60 years) completed a maximum of 6 cycles of treatment with NVG-111 (median=3 cycles [range 1-6 cycles]). Pharmacokinetic and pharmacodynamic data demonstrated systemic NVG-111 exposure and exposure-dependent NVG-111 targeting of ROR1 on circulating tumor cells. Adverse events (AEs) related to NVG-111 occurred in 10 subjects (83%), with the most common being nausea (58%), headaches (67%), and fatigue (33%), majority of which were grade 1 or 2. Grade 1(71%) or 2(29%) cytokine release syndrome (CRS) occurred in 58% of subjects during week 1 of cycle 1 except in one subject who had a second grade 1 CRS in cycle 2. Grade 3 dose limiting toxicities (DLTs) occurred in three subjects (25%) consisting of transient elevation of liver enzymes (ALT and AST) in one subject dosed at 3ug/day, immune effector cell-associated neurotoxicity syndrome-like symptoms (ICANS) in one subject dosed at 30ug/day and headache in one subject dosed at 45ug/day. All AEs were fully reversible with no late emergent grade 3 or greater toxicities. Evidence of T cell activation was observed in all 12 subjects with peak cytokine levels at the 30µg/day dose levels (mean±SEM): TNFα, 43±17pg/ml; IL6, 566±541pg/ml; IFNɣ, 18±12pg/ml; and IL10, 103±56pg/ml. Furthermore, T cell profiling showed an increase in cytotoxic CD8 + T cell activation marker expression during each NVG-111 treatment cycle without evidence of T cell exhaustion. Efficacy was evaluable in 11 subjects with objective clinical responses observed in 55% (6/11), including two subjects with clear evidence of single agent activity. Amongst these, three CLL subjects were rendered MRD negative in peripheral blood and one MCL subject achieved complete metabolic response by the Lugano criteria. Two subjects had stable disease but in one of these subjects there was a &amp;gt;50% reduction in peripheral blood lymphocytosis and a 40% reduction in lymphadenopathy. Despite time limited exposure to NVG-111, the restricted mean survival time for DoR is currently 13.6 months (SEM 3.07), the median is not yet calculable with response ongoing in four subjects. The median progression-free survival currently is 18.7 months (95% CI 2.6 - not calculable). Conclusion: These data provide clinical proof of concept for selective targeting of ROR1 with a TCE leading to objective evidence of antitumor activity with encouraging response durability even in CLL patients known to have defective T cell function. The safety profile was consistent with the mechanism of action. Further evaluation of this promising molecule is ongoing.

Background Molecular characterization of B-cell non-Hodgkin lymphoma (B-NHL), through circulating tumor DNA (ctDNA) assessment of minimal residual disease (MRD) has been proposed as a tool to predict clinical outcome. Odronextamab, a CD20×CD3 bispecific antibody, demonstrated deep and durable responses and a generally manageable safety profile in patients (pts) with R/R FL or DLBCL in the Phase 2 ELM-2 study (NCT03888105; Kim TM et al. and Kim WS et al. ASH. 2022). In the overall populations, 12-month PFS rates were 64% and 29%, respectively. Using ctDNA from ELM-2, we show that these assessments associate with clinical outcomes following odronextamab treatment. Methods In ELM-2, pts received IV odronextamab in 21-day cycles, with step-up dosing in Cycle (C) 1, 80 mg (FL)/160 mg (DLBCL) QW in C2-4, then 160 mg (FL)/320 mg (DLBCL) Q2W until disease progression or unacceptable toxicity. Baseline (BL) ctDNA and tumor biopsies were used for molecular profiling. BL and on-treatment ctDNA were used for MRD determination in the biomarker population (BP; pts required ≥1 available plasma biomarker sample to be included in the BP). The first post-BL ctDNA sample was collected on C5 Day (D) 1, at the time of positron emission tomography-computed tomography (PET-CT). A modified AVENIO ctDNA analysis workflow (Roche; research only) was used for next-generation sequencing, based on the cancer personalized profiling by deep sequencing technique (Kurtz et al. J Clin Oncol. 2018). Whole blood cell pellets were used to filter out germline allele variants. MRD negativity was reported when the P value for variant allele frequency was &amp;gt;0.005. Results The BP comprised 53 FL pts and 63 DLBCL pts; at BL, all FL pts and all but one DLBCL pt were MRD(+). Pts remaining on study until C5D1 had similar PFS regardless of whether they were in the BP or overall population (FL, n=111; DLBCL, n=83). Pts who were MRD(-) at C5D1 had significantly longer PFS vs. those who remained MRD(+) (FL: HR 0.27 [95% CI 0.09-0.84], P=0.024 [Fig. 1a]; DLBCL: HR 0.29 [95% CI 0.12-0.71], P=0.007). In pts with FL achieving complete response (CR) by PET-CT at C5D1, a trend for prolonged PFS was observed in those who were MRD(-) (n=26) at this timepoint vs. those who were MRD(+) (n=17; HR 0.29 [95% CI 0.07-1.1], P=0.072). Pts with DLBCL who were MRD(-) at C5D1 (n=20) had similar PFS benefit regardless of PET-CT CR status (HR 0.56 [95% CI 0.10-3.11], P=0.511). Four DLBCL pts who were MRD(-) and did not achieve CR by PET-CT at C5D1 (partial response, n=3; stable disease, n=1) went on to achieve PET-CT CR at a later timepoint. Mutational analyses of BL ctDNA identified TP53 as the most frequent mutation (FL, n=34/53 [64%] mutation-evaluable pts; DLBCL, n=44/58 [76%]). In FL pts, TP53 mutations were associated with MRD(+) status at C5D1 (Fisher's exact test, P=0.002) and predicted significantly shorter PFS (HR 3.57 [95% CI 1.01-12.69]; P=0.049); this association was not observed in DLBCL. LymphGen classification (Wright et al. Cancer Cell. 2020) of BL ctDNA in pts with DLBCL identified mostly MCD and EZB subtypes (MCD, n=15; EZB, n=14; ST2, n=1; BN2, n=1; other, n=26). EZB-subtype pts treated with odronextamab had significantly longer PFS compared with MCD-subtype pts (HR 0.23 [95% CI 0.07-0.83]; P=0.025 [Fig. 1b]). Using BL ctDNA, cell of origin was determined in 43/58 pts with DLBCL; odronextamab treatment led to similar PFS in higher-risk non-germinal-center B-cell-like (non-GCB, n=18 [42%]) pts vs. GCB pts (n=25 [58%]; HR 1.62 [95% CI 0.72-3.62]; P=0.244). Further molecular assessment focused on gene fusions in DLBCL pts in the BP (39 with local laboratory gene fusion and ctDNA analyses, 24 with only ctDNA analyses). Odronextamab led to similar PFS in pts with double-hit (n=15) or triple-hit (n=5) fusions compared to those without (n=43; P=0.343 and P=0.140, respectively). Conclusions This study is among the first to analyze ctDNA in pts with R/R FL and DLBCL in a pivotal trial. This non-invasive method allows molecular characterization of pts with no available tissue, enabling identification of high-risk subgroups. CtDNA MRD status at C5D1 of odronextamab treatment was highly associated with PFS in pts with FL and DLBCL and in the future could form the basis of response-directed treatment paradigms. Molecular characterization in tumor biopsies, including CD20, will be presented. Ongoing monitoring of ctDNA may serve as an important early progression marker in R/R FL and DLBCL.

Background The class of CD20×CD3 bispecific antibodies (BsAbs) has emerged as an important anti-lymphoma modality for patients (pts) with R/R B-cell non-Hodgkin lymphoma. Odronextamab, a novel, off-the-shelf, CD20×CD3 BsAb, has previously demonstrated compelling efficacy in both R/R diffuse large B-cell lymphoma and R/R FL. In pts with R/R FL, odronextamab monotherapy achieved 75% complete response (CR) rates and encouraging durability of responses, and showed generally manageable safety, in the Phase 2 ELM-2 study (NCT03888105; Kim TM, et al. ASH. 2022). Here, we report the results of a second, pre-specified interim analysis of ELM-2. Methods Intravenous odronextamab was administered weekly in 21-day cycles during Cycles (C) 1-4. Optimization of the step-up regimen to further mitigate cytokine release syndrome (CRS) was reported previously (Kim TM, et al. ASH. 2022). Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during C1, followed by 80 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance treatment continued at 160 mg every 2 weeks until disease progression or unacceptable toxicity. Pts who achieved a durable CR for ≥9 months transitioned to dosing every 4 weeks. A pre-specified interim analysis was performed when 80 pts had completed ≥12 months follow-up. The primary endpoint was objective response rate (ORR), assessed by independent central review (ICR) according to the Lugano classification. Key secondary endpoints included CR rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and changes in scores of patient-reported outcomes. Minimal residual disease (MRD) was included as an exploratory endpoint. Results At data cut off (Jan 31, 2023), the global study was fully enrolled and included 140 safety-evaluable pts with FL; 128 pts were efficacy-evaluable and 85 pts had ≥12 months follow-up. The median duration of study follow-up for efficacy was 26.6 months. In the safety-evaluable FL population, median age was 60.5 years (range 22-84), 53% were male, and pts had received a median of 3 (range 2-13) prior lines of therapy. 73% of pts were refractory to their last therapy, 41% were double refractory, and 74% were refractory to an anti-CD20 antibody. 50% of pts had progression of disease within 2 years (POD24) and 29% had a prior autologous hematopoietic stem cell transplant. ORR and CR rate by ICR were 80% (102/128) and 72% (92/128), respectively, and were consistent across pts with high-risk features. Responses were durable, with both median DoR and duration of CR of 21.7 months; the probability of maintaining CR for 24 months was 48%. Median PFS was 20.7 months (95% CI: 16.7-26.5) and median OS was not reached; the probability of survival at 3 years was 63%. Patient-reported overall quality of life (QoL) scores were maintained during the course of treatment. MRD status at 12 weeks was highly predictive of PFS. Safety was generally consistent with previous reports, and no new treatment-related Grade (Gr) 5 events were recorded since the first interim analysis. The most common treatment-emergent AEs (&amp;gt;30% all grades) were CRS (55%), anemia (34%), neutropenia (34%), and pyrexia (33%). With the optimized 0.7/4/20 mg step-up regimen (n=72), 98% of CRS events were Gr 1/2, and only one pt had Gr 3 CRS. All CRS events resolved with supportive measures; 13 pts received tocilizumab for CRS management with the optimized regimen. Only one low-grade ICANS event was reported with the optimized regimen. Gr ≥3 infections occurred in 50 (36%) pts (Gr 5, n=14 [10%]); COVID-19 infections were reported in 46 (35%) pts (Gr 5, n=8 [6%]). Conclusions The results of this pre-specified analysis of the Phase 2 ELM-2 study continue to demonstrate deep and durable responses with odronextamab in heavily pretreated, refractory pts with R/R FL. 90% of responders were complete responders, with a 48% probability of maintaining CR for 2 years. High CR rates appear to translate to favorable, long-term survival outcomes in the setting of incurable disease. The incidence of AEs was consistent with earlier reports, with no new treatment-related Gr 5 events. Importantly, continued treatment with odronextamab had no detrimental effects on overall QoL. These data underscore the promise of odronextamab as a potentially effective agent for the management of R/R FL. Updated data will be presented.

Background: Goals of patient-centered care for management of relapsed or refractory follicular lymphoma (R/R FL) are to improve clinical outcomes while maintaining or improving health-related quality of life (HRQoL). In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study, odronextamab monotherapy demonstrated high and durable complete response rates and generally manageable safety in patients with R/R FL. We report here, for the first time, patient-reported outcome (PRO) results from ELM-2 in patients with R/R FL. Methods: Patients with R/R FL Grade 1-3a received odronextamab IV at 80 mg weekly in 21-day cycles in Cycles (C) 1-4. Optimization of the step-up regimen to mitigate cytokine release syndrome (CRS) was reported previously. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg in C1, then 80 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance continued at 160 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response (≥9 months) switched to dosing every 4 weeks. Patients completed EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L questionnaires at Weeks 1 (baseline), 2, 3, 4, and 10, then every 8 weeks for the remainder of the first year and every 12 weeks in the second year. Results here focus on six key PRO scales: EORTC QLQ-C30 Global Health Status/Quality of Life (GHS/QOL), physical functioning (PF), role functioning (RF), and fatigue; FACT-Lym lymphoma subscale (LymS); and EQ-5D-3L visual analog score (VAS). Longitudinal analyses using mixed models for repeated measures (MMRM) were conducted through Week 50 (the last visit with ≥10 patients with PRO data). Changes from baseline were considered statistically significant if the 95% confidence interval did not contain zero. No adjustment for multiplicity was performed, hence all statistical significance is nominal. Published ranges for minimum important difference (MID) to define clinically meaningful changes are: EORTC QLQ-C30 scales, 10 points; FACT-Lym LymS, 2.9-5.4 points; and EQ-5D-3L VAS, 7-12 points. For responder and time to definitive deterioration (TTDD) analyses, the upper end of these published MID ranges was used to define deterioration or improvement. Results: At the ELM-2 interim data cutoff on 31-Jan-2023, 140 patients with R/R FL Grade 1-3a had received at least 1 dose of odronextamab. Median age was 60.5 years (range: 22-84), with 38.6% ≥65 years, 52.9% male, 57.1% White, 32.1% Asian, 52.2% ECOG=0, and 47.1% ECOG=1. Median duration of follow-up was 26.6 months (range: 6.2-37.5). PRO completion rates for EORTC-QLQ-C30, FACT-Lym, and EQ-5D-3L were high at baseline and remained high for all assessments through Week 50. At baseline, moderate levels of general health (GHS/QoL) and high levels of functioning (PF and RF) were observed that were higher (better) than reference values for general cancer or non-Hodgkin's Lymphoma (NHL). Fatigue scores at baseline were lower (less symptoms) than reference values for general cancer or NHL. EORTC QLQ-C30 GHS/QOL, PF, RF, and fatigue scores were maintained from baseline through Week 50 (Table). For EQ-5D-3L VAS, the overall estimated mean changes from baseline improved statistically significantly but did not reach MID thresholds (Table). For FACT-Lym LymS, overall estimated mean change from baseline statistically significantly improved, and scores improved statistically significantly from Weeks 10 to 42 (except Week 34), with clinically meaningful improvements at Weeks 26 and 42 (Figure). The proportion of patients reporting meaningful improvement or stability across the six scales was higher than the proportion reporting meaningful worsening through Week 50 (Table). The median TTDD for EORTC-QLQ-C30 GHS/QoL was 22.41 (95% CI: 14.59 to not yet reached) months, corresponding to the median PFS. Median TTDD was not reached for EORTC QLQ-C30 PF, FACT-Lym LymS, and EQ-5D-3L VAS scales. Conclusions: For patients with R/R FL, patient-reported HRQoL results were favorable during odronextamab treatment until disease progression, with no detriments on patient-reported symptoms, functioning, and overall quality of life. These results complement encouraging clinical efficacy, durability of responses, and tolerability observed in this highly refractory patient population and support the future role of odronextamab in the management of patients with R/R FL.

(1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the resection of glioma. Both processes may be enhanced by increasing intracellular PpIX concentrations, which can be achieved through iron chelation. AP2-18 is a novel combinational drug, which ester-links a PpIX precursor (aminolaevulinic acid; ALA) to an iron-chelating agent (CP94). (2) Methods: Human glioma U-87 MG cells were cultured in 96-well plates for 24 h and incubated for 3 or 6 h with various test compound combinations: ALA (±) CP94, methyl aminolevulinate (MAL) (±) CP94 and AP2-18. PpIX fluorescence was measured at 0, 3 or 6 h with a Bio-tek Synergy HT plate reader, as well as immediately after irradiation with a 635 nm red light (Aktilite CL16 LED array), representing the PDT procedure. Cell viability post-irradiation was assessed using the neutral red assay. (3) Results: AP2-18 significantly increased PpIX fluorescence compared to all other test compounds. All treatment protocols effectively achieved PDT-induced cytotoxicity, with no significant difference between test compound combinations. (4) Conclusions: AP2-18 has potential to improve the efficacy of fluorescence-guided resection either with or without the subsequent intraoperative PDT of glioma. Future work should feature a more complex in vitro model of the glioma microenvironment.