BACKGROUND:Sustained-release (SR) tapentadol was listed on Australia's Pharmaceutical Benefits Scheme (PBS) in 2014 for chronic severe pain requiring long-term opioid treatment. Dispensings have increased since listing despite declining trends in other PBS-listed opioids. Preferential prescribing of SR opioids may increase the risk of dependence and accidental overdose, particularly when used to treat acute pain. AIMS:To explore the quality use of publicly subsidised tapentadol in Australia. METHODS:We examined annual initiation rates and patterns of use of tapentadol (SR) in the dispensing records of a 10% random sample of PBS-eligible Australians (2014-2021). We used national tapentadol sales data to assess the proportion of sales attributable to the PBS. RESULTS:Tapentadol initiation increased from 2014, peaking at 7.5/1000 adult population in 2019 before declining to 5.3/1000 in 2021. We identified 63 766 new users between 2014 and 2020, of whom 92.8% discontinued in the first year following initiation, 58.0% had only a single dispensing and 34.3% had no other opioids dispensed in the 3 months before or after initiation. 27.8% of new users were dispensed tapentadol on the same day as potentially interacting medicines. There was a sustained drop in the proportion of sales attributable to the PBS from June 2020 onwards, from an average of 69.1%, to 63.9% of pack sales. CONCLUSIONS:Patterns of use suggest tapentadol (SR) is generally used for short duration. Although most tapentadol sold in Australia is subsidised, there is evidence of a shift towards private sales.

BACKGROUND:Although immunotherapy has emerged as a therapeutic strategy for many cancers, there are limited studies establishing the safety and efficacy in people living with HIV (PLWH) and cancer.METHODS:PLWH and solid tumors or Kaposi sarcoma (KS) receiving antiretroviral therapy and a suppressed HIV viral load received nivolumab at 3 mg/kg every 2 weeks, in two dose deescalation cohorts stratified by CD4 count (stratum 1: CD4 count > 200/µL and stratum 2: CD4 count 100-199/µL). An expansion cohort of 24 participants with a CD4 count > 200/µL was then enrolled.RESULTS:A total of 36 PLWH received nivolumab, including 15 with KS and 21 with a variety of other solid tumors. None of the first 12 participants had dose-limiting toxicity in both CD4 strata, and five patients (14%) overall had grade 3 or higher immune related adverse events. Objective partial response occurred in nine PLWH and cancer (25%), including in six of 15 with KS (40%; 95% CI, 16.3-64.7). The median duration of response was 9.0 months overall and 12.5 months in KS. Responses were observed regardless of PDL1 expression. There were no significant changes in CD4 count or HIV viral load.CONCLUSIONS:Nivolumab has a safety profile in PLWH similar to HIV-negative subjects with cancer, and also efficacy in KS. Plasma HIV remained suppressed and CD4 counts remained stable during treatment and antiretroviral therapy, indicating no adverse impact on immune function.TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02408861.

In this paper, we report a technique for tracking multiple small moving targets using a millimeter-wave Frequency-Modulated Continuous-Wave radar. Radar images are obtained from raw radar data collected by a radar system that performs a digital beamscanning in the azimuth plane and a mechanical beamscanning in the elevation plane. Trajectories of several targets in the scene are estimated from a new multi-target tracking (MT 2 ) algorithm based on the calculation of the global nearest neighbors. We demonstrate the effectiveness of this algorithm from the tracking of two moving targets. Our preliminary experimental results obtained for short range (up to 2.0 meters) outdoor detection of small tags pave the way for future research on tracking tagged flying insects and could therefore be useful for studying the behavior and ecology of pollinators.

This paper is a training paper for aerospace engineering education, given to master students in the Bordeaux's university (https://formations.u-bordeaux.fr/#/details-formation?type=parcours-type&id=1779). It gives the necessary backgrounds for the application of the structured H-infinity control approach to space applications. The structured H-infinity control is presented as a "ready-to-be used" technique. Its theory is not investigated, but some aspects are presented when judged understandable for an engineer. The orbital station-keeping problem is considered as a support example. The paper covers all the aspects of the engineer exercise, from establishing the models for designing the controller until its implementation in a GNC structure. Copyright (C) 2024 The Authors. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Background Prenatal iron deficiency is underrecognized and undertreated. Despite the universally recognized role of iron in maternal health as well as fetal and placental development, US national screening guidelines for prenatal iron deficiency are non-existent. Study Design/Methods A review of published literature pertaining to prenatal iron deficiency was performed; these data were summarized and synthesized to construct an algorithm for the diagnosis and treatment of prenatal iron deficiency. Results Iron deficiency is the most common etiology of anemia in pregnancy and affects over 50% of pregnancies; however, the lack of universal screening undoubtedly underestimates its true prevalence. A ferritin < 30 μg/dL has a 92% sensitivity and 98% specificity for the diagnosis of iron deficiency; remarkably, maternal ferritin < 13.4 μg/dL compromises fetal iron stores. Prenatal iron deficiency invokes significant maternal-fetal consequences: prenatal anemia doubles maternal mortality and is associated with higher rates of preeclampsia, cesarean sections, peripartum hemorrhage, and maternal transfusions; fetal iron deficiency is associated with a higher incidence of intrauterine growth restriction, preterm birth, low birth weight, and unfavorable long-term cognitive and behavioral sequelae (including autism and schizophrenia), the latter persisting despite iron repletion. Optimal iron repletion routes of administration vary by gestational age, with oral iron utilized in the first and second trimesters and the option for intravenous supplementation reserved for the second and third trimesters. While the gastrointestinal tract absorbs a maximum of 5mg of iron per day, the iron requirements in pregnancy are 800mg per day, highlighting the critical role of intravenous supplementation. The 2023 International Federation of Gynecology and Obstetrics (FIGO) guidelines recommend screening all women for iron deficiency starting from menarche, irrespective of anemia, including prior to planned pregnancy and at the end of the second trimester. The 2024 European Hematology Association (EHA) emphasizes and recommends identification of pre-conceptual iron deficiency and normalization of iron stores before conception, along with effective treatment of iron deficiency anemia in pregnancy or postpartum. Unfortunately, the American College of Obstetrics and Gynecology (ACOG) has yet to endorse comparable screening guidance for prenatal iron deficiency. We constructed an algorithm to facilitate early screening, diagnosis, and treatment of iron deficiency in pregnancy that utilizes ferritin as an initial test to screen for iron deficiency, instructions on how to replete iron and when to refer a patient to hematologist. Although our algorithm utilizes ferritin as the principal screening test, transferrin saturation <20% is diagnostic of iron deficiency in the context of inflammation. Conclusion The absence of a United States national recommendation to screen, diagnose, and treat prenatal iron deficiency compromises maternal-fetal outcomes. The adoption of universal iron deficiency screening in all women at first confirmation of pregnancy would lead to earlier recognition and treatment of iron deficiency and improve maternal-fetal outcomes.

Hyperluminous infrared galaxies (HyLIRGs) are the rarest and most extreme starbursts and found only in the distant Universe (z greater than or similar to 1). They have intrinsic infrared (IR) luminosities L-IR >= 10(13) L-circle dot and are commonly found to be major mergers. Recently, the Planck All-Sky Survey to Analyze Gravitationally-lensed Extreme Starbursts project (PASSAGES) searched similar to 10(4) deg(2) of the sky and found similar to 20 HyLIRGs. We describe a detailed study of PJ0116-24, the brightest (mu(LIR) approximate to 2.6 x 10(14) L-circle dot, magnified with mu approximate to 17) Einstein-ring HyLIRG in the southern sky, at z = 2.125, with observations from the near-IR integral-field spectrograph VLT/ERIS and the submillimetre interferometer ALMA. We detected H alpha, H beta, [N II] and [S II] lines and obtained an extreme Balmer decrement (H alpha/H beta approximate to 8.73 +/- 1.14). We modelled the molecular-gas and ionized-gas kinematics with CO(3-2) and H alpha data at similar to 100-300 pc and (sub)kiloparsec delensed scales, respectively, finding consistent regular rotation. We found PJ0116-24 to be highly rotationally supported (v(rot)/sigma(0, mol. gas) approximate to 9.4) with a richer gaseous substructure than other known HyLIRGs. Our results imply that PJ0116-24 is an intrinsically massive (M-baryon approximate to 10(11.3) M-circle dot) and rare starbursty disk (star-formation rate, SFR = 1,490 M-circle dot yr(-1)) probably undergoing secular evolution. This indicates that the maximal SFR (greater than or similar to 1,000 M-circle dot yr(-1)) predicted by simulations could occur during a galaxy's secular evolution, away from major mergers.

Objectives: This study evaluated real-world treatment patterns of approved bone-targeting agents (BTAs) with various mechanisms of action—pamidronate, zoledronic acid, and denosumab—for the prevention of skeletal-related events in patients with bone metastases (BM) from solid tumors. Methods: Adult patients with BM secondary to solid tumors between January 1, 2014, and December 31, 2018, were identified from the Flatiron Health Oncology Services Comprehensive Electronic Records database and categorized by BTA use and therapy type. Time from diagnosis to initiation, persistence (mean time on treatment), and compliance (≥12 administrations/year) with BTA with up to 4 years of follow-up were examined. Results: This study included 27,268 patients with BM (breast cancer, 32.7%; lung cancer, 16.5%; prostate cancer, 17.2%; and other solid tumors, 33.6%); of these, 41.4% initiated denosumab after BM diagnosis; 21.3%, zoledronic acid; 0.6%, pamidronate; and 36.7% had no treatment record. Mean (SD) time to initiation for denosumab or zoledronic acid was 68.6 (157.0) days (denosumab, 70.3 (160.4) days; zoledronic acid, 65.2 [150.2] days). Mean persistence and compliance (first year of treatment) were significantly higher for denosumab than for zoledronic acid (22.0 vs. 14.9 mo [ P <0.0001] and 42.3% vs. 34.8% [ P <0.0001], respectively). Treatment compliance was the highest in patients with breast cancer (denosumab, 48.2%; zoledronic acid, 39.1%). Conclusions: Real-world BTA treatment patterns in the United States suggest that over one-third of patients with BM secondary to solid tumors remain untreated and less than 50% of the patients received ≥12 administrations/year of BTA therapy.

In this paper, we propose to combine the two-dimensional MUSIC (MUltiple SIgnal Classification) algorithm with Fast Fourier Transform (FFT) to detect small moving targets from raw data collected by millimeter-wave beamscanners. It is shown that this hybrid detection method makes it possible to reduce by factor 3 the computation time required by MUSIC algorithm, at the expense of the reduction by 55% of the detection rate. Measurement results and analyses are given in the case of the tracking of a small mobile cylinder in a cluttered indoor environment from three millimeter-wave beamscanning radars.

In patients with lower-risk myelodysplastic syndromes/neoplasms (MDS), response to first-line therapy is limited and transient. The MATTERHORN randomized, double-blind, phase 3 trial evaluated roxadustat versus placebo for patients with transfusion-dependent, lower-risk MDS. Eligible patients had very low-, low-, or intermediate-risk MDS with or without prior erythropoiesis-stimulating agent treatment, and a transfusion burden of 1-4 packed red blood cell (pRBC) units every 8 weeks (Q8W). Patients were randomized (3:2) to oral roxadustat (2.5 mg/kg) or placebo, both three times weekly, with best supportive care. Primary efficacy endpoint was transfusion independence (TI) for ≥56 days within 28 weeks (TI responders). MATTERHORN was terminated due to interim analysis outcomes not meeting statistical significance. In total, 272 patients were screened, and 140 patients were enrolled (82, roxadustat, and 58, placebo). At final analysis, 38/80 (47.5%) patients and 19/57 (33.3%) in the roxadustat and placebo arms, respectively, were TI responders (p = .217). A greater percentage of patients in the roxadustat arm with a transfusion burden of ≥2 pRBC units Q4W were TI responders (36.1%; 13/36) compared with the placebo arm (11.5%; 3/26; p-nominal = .047). The seven on-study deaths (4, roxadustat, and 3, placebo) were considered unrelated to treatment. Three roxadustat patients progressed to acute myeloid leukemia. Despite MATTERHORN not meeting its primary endpoint, a numerically higher TI rate was achieved with roxadustat treatment compared with placebo. Further analyses are needed to confirm the MDS patient subgroups deriving clinical benefit from this novel treatment.

Multiple unmanned aerial vehicle (UAV) cooperative operations have been proposed as a relatively new concept for improving the combat capability of a single UAV, and formation control is the focus and core technology of multi-UAV cooperative operations. However, the existing control methods rarely focus on the optimization of UAV formation based on constrained effectiveness, and faster tracking performance is required in formation control. Therefore, this study presents a 6 degrees-of-freedom UAV formation control architecture that integrates trajectory planning and attitude control by considering the constrained effectiveness of optimal formation and coupling effect. To achieve formation selection and geometry parameter optimization in a battlefield environment, a formation-constrained effectiveness model based on battlefield effectiveness was proposed, and the formation was optimized using the simulated annealing particle swarm optimization (SAPSO) method. To verify the accuracy and effectiveness of formation optimization and control, five UAV formation flight scenarios based on combat effectiveness formation were designed. Numerical simulation results show that the proposed optimization algorithm can maximizes battlefield effectiveness based on the formation-constrained effectiveness model; the proposed trajectory planning accurately tracked the relative position commands with a fast response time and short rising time; the proposed coupling effect-involved attitude control method was compared with the conventional attitude control method to demonstrate the efficiency of the proposed method; and the controller considering coupling had a faster trajectory response in the coupling effect zone. These results suggest that the proposed approach has a better tracking performance and demonstrates high efficiency and accuracy in UAV formation control.

Introduction: Autologous Stem Cell Transplantation (ASCT) offers high curative rates for patients with Multiple Myeloma (MM), Hodgkin's Lymphoma (HL), and non-Hodgkin's Lymphoma (NHL). Optimization of blood counts prior to ASCT is important to avoid prolonged pancytopenia following conditioning chemotherapy, and to minimize post-transplant complications and mortality. Pennsylvania Hospital's Centre for Transfusion-Free Medicine (CTFM) performed the world's first bloodless ASCT more than 20 years ago utilizing cell adjuncts such as erythropoietin (EPO), intravenous iron, aminocaproic acid, and granulocyte colony-stimulating factor (G-CSF). While there exist no clear guidelines as to a specific hemoglobin level to maintain prior to transplantation, practices often vary with a pre-transplant hemoglobin of 11-12g/dL being recommended from prior literature. We conducted a review of all bloodless medicine patients' hemoglobin levels enrolled at the CTFM with MM, HL, and NHL undergoing autologous stem cell transplantation. Methods: This retrospective single-center study included all bloodless medicine patients ≥ 18 years old with HL(n=4), NHL (n=11) and MM (n=44) who received ASCT between January 2016 - December 2023 at Pennsylvania Hospital's CTFM. All patients included were inpatient hospitalization encounters for complete blood count (CBC) monitoring following outpatient stem cell collection, conditioning chemotherapy, and stem cell reinfusion. Patients not admitted post-stem-cell infusion were excluded. Data points were manually extracted through chart review and included hemoglobin values in g/dL on admission, discharge and lowest value recorded during admission; length of stay in days; and 30-day post-reinfusion mortality status. Our primary endpoint was to determine mortality rates stratified by hemoglobin ranges per 1.0g/dL prior to admission. A secondary objective was to determine patients' average length of stay (LOS) stratified based on hemoglobin values prior to admission. Results: 59 patients with either MM, HL, or NHL were included, no patients were excluded from our CTFM database. The average age of patients was 58.5 years. The average hemoglobin on admission for all patients was 12.3g/dL, while the average hemoglobin on discharge was 9.3g/dL, constituted as grade 1 anemia per Common Terminology Criteria for Adverse Events (CTCAE). The average nadir hemoglobin among all patients was 8.2g/dL. Hemoglobin decreased an average of 4.2g/dL from admission to nadir, and 42% of patients experienced grade 3 anemia during nadir (25/59). Of these 25 patients, 14 patients (56%) had improvement in hemoglobin levels above 8.0g/dL on discharge. A single 30-day post-reinfusion death secondary to treatment-related mortality from profound anemia occurred in a patient with a hemoglobin of 2.8g/dL (grade-4 anemia) in the intensive care unit, who had an admission hemoglobin of 11.2g/dL. The average LOS for all patients was 19.2 days. Sub-group analysis of all patients showed that 5% of patients had hemoglobin values between 9-10g/dL, 10% between 10-11g/dL, 27% between 11-12g/dL, and 57% above 12g/dL on admission. Of these patients, 30-day mortality rates within all sub-groups were 0%, as determined by living status at 30-days post-reinfusion, except for a 6.25% mortality rate (1/16) within the 11-12g/dL group. Among patient subgroups stratified by hemoglobin on admission, there was no statistical difference in length of stay (ANOVA p=0.8), nor 30-day post-reinfusion mortality rates (ANOVA p=0.7). Discussion: ASCT for bloodless medicine patients has been increasingly accessible over the past decade due to improvement in strategies for pharmacologic support pre-transplantation, effective cytokine mobilization, reducing bleeding events, and close cardiac monitoring. Our single-center data analysis suggests that bloodless medicine patients may, in-fact, have a higher tolerance of anemia ahead of conditioning chemotherapy for ASCT compared to previous evidence. Given a lack of significant difference in mortality rates between patients with admission hemoglobin levels as low as 9.7g/dL and higher levels, we believe ASCT can be safely performed in select patients with hemoglobin values below 11g/dL with close inpatient CBC monitoring and treatment with cell adjuncts.

ERIS, the Enhanced Resolution Imager and Spectrograph, is an instrument that both extends and enhances the fundamental diffraction limited imaging and spectroscopy capability for the VLT. It replaces two instruments that were being maintained beyond their operational lifetimes, combines their functionality on a single focus, provides a new wavefront sensing module for natural and laser guide stars that makes use of the Adaptive Optics Facility, and considerably improves on their performance. The observational modes ERIS provides are integral field spectroscopy at 1-2.5 μm, imaging at 1-5 μm with several options for high contrast imaging, and longslit spectroscopy at 3-4 μm, The instrument is installed at the Cassegrain focus of UT4 at the VLT and, following its commissioning during 2022, has been made available to the community.

Presented on behalf of all MATTERHORN (FGCL-4592-082) study investigators Introduction: For patients (pts) with LR-MDS, anemia poses a major clinical challenge, with limited response to first-line erythropoietin (EPO)-stimulating agents (ESAs) and a median duration of response ≤2 years. Further, pts with RBC transfusion dependence (≥2 packed RBC [pRBC] units every 8 weeks [Q8W]) are less likely to respond to ESAs. Anemia treatments with novel mechanisms of action enabling transfusion independence (TI) are needed to reduce frequent RBC transfusion burden. Roxadustat is a first-in-class, hypoxia-inducible factor prolyl hydroxylase inhibitor for treatment of anemia with chronic kidney disease. In the MATTERHORN (NCT03263091) dose-selection stage, roxadustat was well-tolerated, and 37.5% of pts (9/24) with LR-MDS and low RBC transfusion burden ([LTB] 1 pRBC unit Q8W for two consecutive 8-week periods or 2-4 pRBC units Q8W) achieved TI. In the MATTERHORN double-blind stage, TI response rate and safety of roxadustat were further assessed. Methods: MATTERHORN is an ongoing, double-blind, Phase III, randomized, placebo (PBO)-controlled trial. Eligible adult pts (≥18 years of age) had very low-, low-, or intermediate-risk primary MDS per Revised International Prognostic Scoring System (IPSS-R) classification (<5% bone marrow blasts); hemoglobin (Hb) ≤10.0 g/dL at baseline (BL); and LTB. Prior ESA use (>8 weeks before randomization) was permitted. Pts were randomized 3:2 to roxadustat or PBO, then stratified by serum EPO concentration (≤200 or 200-400 mIU/mL), IPSS-R risk, and transfusion burden. Pts received oral roxadustat (starting dosage: 2.5 mg/kg three times weekly based on the dose-selection stage) or PBO with best supportive care (BSC; per institutional criteria, including RBC transfusion) for a 52-week treatment period, followed by a 4-week follow-up period. Primary efficacy endpoint was percentage of pts with TI (the absence of RBC transfusion) for ≥56 consecutive days during the first 28 treatment weeks (TI responder). The percentage of pts with TI and mean Hb increase of ≥1.0 and ≥1.5 g/dL (averaged over 8 weeks) compared with BL pretransfusion Hb was also assessed (to be reported separately). Safety (including treatment-emergent adverse events [TEAEs] and serious TEAEs) was evaluated throughout the study. Results: As of the final 28-week interim analysis of the double-blind stage (data cutoff: April 24, 2023), 140 pts (82 roxadustat, 58 PBO) were randomized and treated. Across arms, median age was 71.5 years (range, 26-96), 59.3% (83/140) were male, and 80.0% (112/140) were white. Most pts (72.1% [101/140]) had IPSS-R low-risk disease and a transfusion burden of 2-4 pRBC units Q8W (92.1% [129/140]). Median (range) BL transfusion burden was 2.5 (1-10) pRBC units. Seventy pts (50.0%) received prior ESAs (98.6% [69/70] were ESA-refractory). Eighty-four pts (41/82 [50.0%] roxadustat, 43/58 [74.1%] PBO) completed 28 weeks of treatment, and 15 pts (6/82 [7.3%] roxadustat, 9/58 [15.5%] PBO) were continuing treatment. Median (range) treatment duration was 24.1 (1.1-28.0) weeks for the roxadustat arm and 28.0 (0.1-28.0) weeks for the PBO arm. A greater percentage of pts in the roxadustat arm compared with the PBO arm were TI responders (47.5% vs. 33.3%). However, this difference did not reach statistical significance ( p=0.22; figure). Percentages of pts with TEAEs of any grade, serious TEAEs, and TEAEs leading to treatment discontinuation were similar across arms (table). Six deaths occurred on study (roxadustat: pneumonia [n=2], acute myocardial infarction and ischemic stroke [n=1], multiorgan failure [n=1]; PBO: urosepsis [n=1], disease progression [n=1]). Three pts (all in roxadustat arm) progressed to acute myeloid leukemia. The study was terminated by the sponsor and is currently being completed. Conclusions: Despite not meeting the primary endpoint, roxadustat plus BSC was well-tolerated, and a high percentage of pts with LR-MDS and LTB were TI responders. The high TI response rate in the PBO arm, historically poor outcomes in pts with ESA-refractory disease, and the inclusion of pts who were not transfusion-dependent (1 pRBC unit Q8W) may have contributed to the lack of a statistically significant difference in TI response rates between arms. MATTERHORN outcomes highlight the continued unmet need for effective and safe therapies that reduce RBC transfusion burden in LR-MDS.

12085 Background: Anemia is prevalent in patients (pts) receiving myelosuppressive chemotherapy (> 60%) and exacerbated by repeated treatment cycles due to cytotoxic agent accumulation. Chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in pts with anemia receiving myelosuppressive chemotherapy. Methods: This open-label, single-arm, proof-of-concept Phase 2 study included pts with mostly advanced, non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had not received red blood cell (RBC) transfusion or erythropoietin-stimulating agents within 4 weeks of enrollment. Patients were treated with oral roxadustat for ≤16 weeks. The primary efficacy endpoint was maximum mean change in Hb within 16 weeks of baseline without RBC transfusion in pts who had received ≥1 dose of roxadustat and who had a baseline and ≥1 post-dose Hb assessment. Hb response and safety data were preliminarily assessed in pts receiving a starting dose of 2.0 mg/kg thrice weekly (TIW) for 4 weeks: doses of 100, 150, and 200 mg were given to pts weighing < 70, 70–100, and > 100 kg, respectively. Following a review of data from these pts, dose was increased to 2.5 mg/kg—150, 200, and 250 mg TIW to pts weighing < 70, 70–100, and > 100 kg, respectively—and adjusted every 4 weeks from Week 5 based on Hb response. Results: Patients were assigned to 2.0 mg/kg (n = 31) and 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The maximum mean Hb change from baseline without RBC transfusion was 2.47±1.51 g/dL and 2.52±1.54 g/dL in the 2.0 mg/kg and 2.5 mg/kg cohorts, respectively. Hb increased by ≥1.5 g/dL in 73% of pts and ≥2.0 g/dL in 61% of pts. Median time to ≥2.0 g/dL Hb increase was 71.0 days. Both cohorts had higher proportions of pts with a Hb increase of ≥1, ≥1.5, or ≥2 g/dL at Week 16 compared with baseline. Median time to ≥1 and ≥2 g/dL Hb increase was shorter in pts who started on 2.5 mg/kg compared with 2.0 mg/kg doses (≥1 g/dL: 30 vs 44; ≥2 g/dL 57 vs 105, respectively). Fewer pts required an RBC transfusion (Week 5 to end of treatment) when starting on 2.5 mg/kg compared with 2.0 mg/kg doses (10.2% vs 20.0%). Subgroup analyses based on major tumor and baseline chemotherapy types demonstrated efficacy of roxadustat at both starting doses. The overall safety profile observed was consistent with the patient population under study. Overall, 92% of pts experienced an adverse event (AE). Most AEs were consistent with the underlying malignancies and chemotherapy regimens used. The incidence of deep vein thrombosis was 15.2% (n = 14) and pulmonary embolism was 9.8% (n = 9). There were 17 deaths (18.5%) during the study; none were attributed to roxadustat, and most were associated with disease progression. Conclusions: Roxadustat increased Hb in CIA regardless of tumor type and chemotherapy regimen. These data support additional clinical study. Clinical trial information: NCT04076943.

<p>Supplementary Figure S1: Combined patient population and treatments in the three phase III studies included in the analysis. Supplementary Figure S2: OS (A), DP (B), and DPB (C) stratified by category ({greater than or equal to} or < median) of month 3 sBSAP percent change from baseline. Supplementary Table S1: BTM levels at baseline and at month 3 after bone antiresorptive treatment. Supplementary Table S2: Covariate analysis of OS, DP, and DPB at month 3 adjusted for baseline visceral metastases, bone metastases, or ECOG category.</p>

Background Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions. Methods We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4(+) T-cell count of 50 cells per mu L or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1 center dot 2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107. Findings Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection. Interpretation Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained. Copyright (c) 2023 Elsevier Ltd. All rights reserved.

OBJECTIVES:This study evaluated real-world treatment patterns of approved bone-targeting agents (BTAs) with various mechanisms of action-pamidronate, zoledronic acid, and denosumab-for the prevention of skeletal-related events in patients with bone metastases (BM) from solid tumors. METHODS:Adult patients with BM secondary to solid tumors between January 1, 2014, and December 31, 2018, were identified from the Flatiron Health Oncology Services Comprehensive Electronic Records database and categorized by BTA use and therapy type. Time from diagnosis to initiation, persistence (mean time on treatment), and compliance (≥12 administrations/year) with BTA with up to 4 years of follow-up were examined. RESULTS:This study included 27,268 patients with BM (breast cancer, 32.7%; lung cancer, 16.5%; prostate cancer, 17.2%; and other solid tumors, 33.6%); of these, 41.4% initiated denosumab after BM diagnosis; 21.3%, zoledronic acid; 0.6%, pamidronate; and 36.7% had no treatment record. Mean (SD) time to initiation for denosumab or zoledronic acid was 68.6 (157.0) days (denosumab, 70.3 (160.4) days; zoledronic acid, 65.2 [150.2] days). Mean persistence and compliance (first year of treatment) were significantly higher for denosumab than for zoledronic acid (22.0 vs. 14.9 mo [ P <0.0001] and 42.3% vs. 34.8% [ P <0.0001], respectively). Treatment compliance was the highest in patients with breast cancer (denosumab, 48.2%; zoledronic acid, 39.1%). CONCLUSION:Real-world BTA treatment patterns in the United States suggest that over one-third of patients with BM secondary to solid tumors remain untreated and less than 50% of the patients received ≥12 administrations/year of BTA therapy.

Background: Multiple cases of immune thrombocytopenia (ITP) occurring after SARS-CoV-2 mRNA vaccines have recently reached public attention. It has been reported in patients with previous ITP or other autoimmune diseases and in individuals with no associated past medical history. The management, and the recurrence of ITP with booster doses are still not well investigated and remains a challenge for clinicians. Aims: To report potential benefit of Thrombopoietin receptor agonist (TPO) following immune thrombocytopenia (ITP) associated with COVID-19 vaccination. Methods: Case report. Results: A 36-year-old previously healthy woman presented with a 5-day history of menorrhagia, epistaxis, gingival bleeding, and petechial rash in extremities. The patient received her first dose of the BNT162b2 COVID-19 Vaccine two weeks before symptom onset. Laboratory workup on admission revealed a platelet count of less than 4,000/ml, hemoglobin of 14.7 g/dL, and white blood cell count of 10,900/mL. A peripheral smear confirmed severe thrombocytopenia with no schistocytes. Additional studies showed normal prothrombin time, partial thromboplastin time, basic metabolic panel, folate, B12, and Thyroid-stimulating hormone. Given the clinical and laboratory findings, the patient was diagnosed with Idiopathic thrombocytopenic purpura (ITP). She was started on a three-day course of Intravenous immune globulin (IVIG) 1 g/kg/d and methylprednisolone 60 mg/d, after which her symptoms improved and the platelet count increased to 80,000/ml. The patient was discharged three days after admission on a four-day prednisone taper plan. She was started on Eltrombopag 50 mg daily two weeks after discharge and received her second dose of the COVID-19 vaccine three weeks after discharge without any adverse reaction. Her platelet count was 356,000/ml at the time of initiation of Eltrombopag and increased to 668,000/mL after the completion of four weeks of treatment (three weeks after the second dose of vaccination). In a follow-up appointment three weeks after discontinuation of Eltrombopag, she denied any recurrent symptoms of bleeding or menorrhagia, and her platelet count was normal (371,000/ml). Image:Summary/Conclusion: Multiple cases of thrombocytopenia have been reported in recipients of both BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 Vaccines so far, with a reported incidence rate of 0.80 per million doses for both vaccines. Based on an annual incidence rate of 3.3 ITP cases per 100,000 adults, the observed number of all thrombocytopenia cases following administration of mRNA COVID-19 vaccines does not exceed the number of expected ITP cases. Symptomatic ITP is a severe condition that carries the risk of fatal hemorrhage and is generally treated with corticosteroids and/or IVIG. In refractory disease, splenectomy, or administration of TPO agonists can be considered. In patients with vaccine associated ITP, using TPO agonists earlier might be considered to avoid the use of immunosuppressants shortly after vaccination, which might impair the intended immunity against SARS-CoV-2.

Introduction: Immune/idiopathic thrombocytopenia purpura (ITP) is a condition characterized by low platelet counts. Current chronic treatment options for ITP include rituximab, a thrombopoietin (TPO) agonist, or a splenectomy. Rituximab, a CD20 monoclonal antibody that depletes B-cells to disrupt the production of harmful antibodies (Zaja et al. 2003), has historically been the primary treatment for ITP. However, early studies have shown that while effective in the short term, rituximab has a drop in efficacy after 180 days (Zaja et al. 2003). TPO agonists are a newer mechanism that mimic endogenous TPO by stimulating the maturation and proliferation of megakaryocytes to stimulate platelet production (Nugent et al. 2009). Current TPO agonists include avatrombopag, eltrombopag, fostamatinib, and romiplostim. We explored the use of these TPO agonists practically in the hematology/oncology practice at Pennsylvania Hospital (PAH) to evaluate efficacy and responses to each therapy. Methods: A retrospective chart review was conducted through the University of Pennsylvania Epic system investigating chronic treatment of ITP at PAH hematology/oncology department since 2012 with a diagnosis of ITP. Results: 231 charts were analyzed. 121 patients did not require chronic treatment (1 patient was admitted for workup while the chart review occurred, and treatment is still being determined). 10 had chronic treatment via steroids, mainly prednisone, and 1 only had a family history of ITP with no ITP diagnosis. 8 charts were unable to be reviewed due to privacy concerns. This left 91 charts which were reviewed for chronic management of ITP. Of these 91 charts, 7 only presented for a second opinion on management and did not receive treatment. 15 underwent a splenectomy, but only 3 did not first receive a secondary therapy. 48 received rituximab, but only 15 (31.25%) had a sustained response. 66 patients eventually received a TPO agonist. Of these 66 patients, only 22 (33.33%) received a single therapy. The other 44 received multiple TPO agonists or rituximab and then a TPO agonist. All four TPO agonists were used, and the responses to these drugs are summarized in table 1. Conclusions: Of the 231 patients presenting to the PAH hematology/oncology clinic, 91 required long term, non-steroidal therapy. Our findings support previous studies that show a decline in long term efficacy of rituximab with only 31.25% (15) of patients achieving a sustained response. The other 68.65% (33) required an additional therapy. Interestingly, all 3 secondary therapies (rituximab, TPO agonist, and splenectomy) were utilized by the clinicians and 72.5% (66) of patients required a TPO agonist. About one-third (22) of these 66 patients had a sustained response on a single TPO agonist on their first try. However, two-thirds (44) of the patients had to switch to another TPO agonist before finding an acceptable response. Eltrombopag and romiplostim are relatively older than fostamatinib and avatrombopag, however the newer drugs are beginning to make their way into therapy with 5 patients on ongoing therapy with fostamatinib (3) and avatrombopag (2). The downfall of the TPO agonists is that most require sustained long-term therapy with only 5 patients total achieving a sustained response without therapy. This is especially difficult for romiplostim which requires patients to come in weekly for an injection. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal