bluuebunny/crossref_metadata_2025_split huggingface dataset:
The treatment of Austrian private foundations under the Ultimate Beneficial Ownership Act
Authors: Petritz Michael , Horkel-Wytrzens Cordula 
Published: June 2019

Abstract
As part of the implementation of the fourth Anti-Money Laundering Directive in Austria, the Wirtschaftliche Eigentümer Register Gesetz, (The Ultimate Beneficial Owner Register Act) was introduced. The main aim of this Act is to provide accurate and up-to-date information on the ultimate beneficial owner (UBO) of entities, trusts, and foundations. This information is seen as a key factor in combating money laundering and terrorist financing. Paragraph 2 of the Ultimate Beneficial Ownership Act defines the UBO, which corresponds to the definition in paragraph 3 subparagraph 6 of the Anti-Money Laundering Directive. In the case of corporate entities, ultimate ownership and control are relevant for determining the UBO. In the case of trusts and private foundations, it is not ownership and control that are relevant for determining the UBO, but the function the person has with respect to the trust/foundation. All definitions have in common that the UBO has to be a natural person. Obliged entities are required to identify and report their UBOs to the register, in the case of a breach of duty/law severe penalties apply.
Include, Individualize, and Integrate: Organizational Meta-strategies for Mature Workers
Authors: Parker Sharon K , Andrei Daniela M 
Published: June 2019

AbstractIn this commentary, we synthesize the literature on mature workers in organizations to support the development of an intervention-focused research program. We identify 3 broad approaches, or “meta-strategies,” which theory and research suggest organizations can use to reap the benefits associated with a mature and age-diverse workforce. “Include” involves strategies to create an inclusive climate in which mature workers are welcomed and fairly treated and is based on theories such as optimal distinctiveness theory. “Individualize” involves strategies to adapt the work to meet the individual needs and preferences of an aging workforce, such as work redesign and is based on theories about how people change over the life span. “Integrate” involves strategies to address the greater age diversity that comes with an aging workforce, such as how mentoring schemes enable younger and older workers to better learn from each other, and is based on theories such as those concerned with team diversity. We believe that this framework will help organizational decision makers to think more broadly and more proactively about how to manage, and harness the benefits of, an aging workforce. Our framework also challenges researchers to give more attention to intervention studies, including considering what configurations of strategies might be most helpful, as well as whether sequencing of strategies is important.
PF288 POPULATION PHARMACOKINETIC (POPPK) AND CONCENTRATION‐QTC ANALYSIS OF QUIZARTINIB IN PATIENTS (PTS) WITH FLT3‐ITD–POSITIVE RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML)
Authors: Kang D. , Ludwig E. , Jaworowicz D. , Huang H. , Fiedler‐Kelly J. , Cortes J. , Ganguly S. , Khaled S. , Krämer A. , Levis M. , Martinelli G. , Perl A. , Russell N. , Abutarif M. , Choi Y. , Kobayashi K. , Mendell J. , Yin O. 
Published: June 2019

Background:Quizartinib is a highly potent and selective FLT3 inhibitor with robust clinical activity in pts with R/R FLT3‐ITD AML.Aims:This analysis was conducted to evaluate the PopPK with quizartinib in a pooled analysis of 7 trials and to evaluate the relationship of quizartinib concentration to QTc in patients from the phase 3 QuANTUM‐R (AC220–007) study.Methods:The PopPK analysis included data from 585 participants enrolled in 5 phase 1 studies, 1 phase 2 study (2689‐CL‐2004), and 1 phase 3 study (QuANTUM‐R). Quizartinib was given as single or multiple doses of 20, 30, 60, and 90 mg (17.7, 26.5, 53, 79.5 mg free base). In QuANTUM‐R, the starting dose was 30 mg/day, increased to 60 mg/day after 2 weeks if QTcF was <450 ms. Patients receiving a concurrent strong CYP3A inhibitor initiated quizartinib at 20 mg/day, with an increase to 30 mg/day if QTcF was <450 ms. Concentration‐QTc analysis included only QuANTUM‐R pts (n = 226). Nonlinear mixed‐effects modeling was performed using observed quizartinib concentrations and time‐matched triplicate ECG measurements.Results:Only strong CYP3A inhibitor use produced a meaningful effect on quizartinib overall exposure (AUC)—an approximately 62% increase. Participant status (AML pts vs healthy participants), albumin level, and body surface area were statistically significant factors, but their effects on quizartinib AUC were <20%. QTcF increased in a concentration‐dependent manner, and the predicted mean increase at the maximum concentration of 60 mg was 21.1 ms (90% CI, 18.3–23.6 ms). Hypokalemia (serum potassium <3.5 mmol/L) was a statistically significant covariate affecting baseline QTcF, but no differences in QTcF increase would be expected at the same quizartinib concentration between patients with and those without hypokalemia.Summary/Conclusion:Strong CYP3A inhibitor use was the only clinically meaningful factor affecting quizartinib PK exposure. QTcF showed an exposure‐dependent increase with respect to quizartinib concentration; but no significant factors, including sex and age, were identified affecting the concentration‐QTc relationship. Results support clinical recommendation of dose reduction in pts receiving strong CYP3A inhibitors because quizartinib exposure is increased significantly in the presence of such agents.
PF316 THE CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH AGGRESSIVE LARGE CELL LYMPHOMA AND DIABETES MELLITUS
Authors: Pasvolsky O. , akirov A. , elias B. , raanani P. , gurion R. , rozovski U. 
Published: June 2019

Background:Epidemiological studies suggest that patients with diabetes mellitus (DM) are at‐risk to develop several types of cancers, including non‐Hodgkin lymphoma. Whether DM affects the clinical presentation or outcome of patients with lymphoma is unknown. Since patients with DM are prone to develop infectious complications, we hypothesize that the co‐occurrence of DM would increase the rate and/or severity of infectious complications in patients with lymphoma who receive chemotherapy.Aims:To describe the clinical characteristics and outcomes of patients with DM who received treatment for aggressive large cell lymphoma.Methods:This is a single center retrospective single center study. We included all consecutive patients who were diagnosed with aggressive large cell lymphoma and were treated at our institute between 2013 and 2017. Demographics, disease‐related and outcome data were extracted from the electronic medical records. Additional data and lab results were extracted from the hospital database. Categorical variables were compared using the χ2 or the Fischer exact test, and Mann Whitney was used to compare medians.Results:Between the years 2013 and 2017 we treated 226 patients with aggressive large cell lymphoma, most (n = 219, 96%) with diffuse large B cell lymphoma. In this cohort 49 patients (22%) had type 2 DM. None of our patients had type 1 DM. The median age of patients with DM was 70 years, and of non‐DM patients 65 years (P = 0.001). Patients with DM tended to have higher baseline BMI values (P = 0.057), but were comparable in all other demographic characteristics. Likewise, response to therapy, relapse rates and survival outcomes were similar in patients with DM compared to non‐DM patients.There were 133 hospital admissions due to febrile neutropenia (FN) in the entire cohort. Patients with DM had higher rates of admissions due to FN (P = 0.004). The admission rate in patients with DM remained higher after age‐matched subgroup analysis (P = 0.005). Yet, the duration of hospitalizations and number of admissions to the ICU were similar in patients with or without DM. In patients with DM, improved glycemic control during FN hospitalizations was associated with shorter hospital duration (P = 0.007). However, Hemoglobin A1C levels were not associated with increased risk for FN or infectious complications.Summary/Conclusion:Patients with aggressive large cell lymphoma and DM have higher rates of hospitalizations due to FN. In this high risk population, perhaps more aggressive measures should be made to avoid infectious complications. Furthermore, our data suggests that improved glycemic control during hospitalization is associated with shorter length of hospitalization due to FN in patients with DM.
PF333 RISK OF BLEEDING COMPLICATIONS AND ATRIAL FIBRILLATION ASSOCIATED WITH IBRUTINIB TREATMENT: A SYSTEMATIC REVIEW AND META‐ANALYSIS
Authors: Pellegrini L. , Novak U. , Andres M. , Nagler M. 
Published: June 2019

Background:The use of ibrutinib is rapidly increasing because of its high potency to treat chronic lymphocytic leukaemia and other lymphoproliferative disorders. The application is however hampered by major adverse events such as bleeding complications and atrial fibrillation. The frequency and predictors of these adverse events are unknown.Aims:We aimed to study the frequency and predictors of bleeding complications and atrial fibrillation in patients treated with ibrutinib.Methods:Following a prespecified protocol, we systematically searched the literature for case series, cohort studies, as well as randomized controlled trials reporting on patients treated with ibrutinib using MEDLINE and EMBASE databases. We retrieved all relevant data in parallel. Methodological quality was observed using the Newcastle‐Ottawa Scale (NOS). Proportions of patients with bleeding events as well as atrial fibrillation were pooled in relevant subgroups using the binominal distribution and Freeman‐Tukey double arcsine transformation.Results:Among 1870 records screened, and 263 articles assessed in full‐text, 58 were finally included, comprising 4918 patients treated with ibrutinib. Methodological quality according to NOS was rated as poor to moderate. Bleeding events varied substantially with any bleedings reported between 2.8% and 78%, and major bleedings between 0% and 25% (Figure 1). New onset of atrial fibrillation was reported between 0% and 11%. Pooled estimates were 25% for any bleedings (95% confidence interval [CI] 19%, 32%); 3% for major bleedings (95% CI 2%, 4%), and 5% for atrial fibrillation (95% CI 4%, 6%). Predictors of adverse events were not apparent.Summary/Conclusion:Reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained suggests a relevant risk of bleeding events as well as atrial fibrillation in patients treated with ibrutinib.image
PF413 CARDIAC, VASCULAR, AND HYPERTENSION SAFETY OF BOSUTINIB VS IMATINIB FOR NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA IN THE BFORE TRIAL
Authors: Brümmendorf T.H. , Gambacorti‐Passerini C. , Clark R. , Leip E. , Viqueira A. , Kota V. , Deininger M. , Cortes J.E. 
Published: June 2019

Background:Tyrosine kinase inhibitor therapy has been linked to cardiac and vascular events.Aims:Cardiac, vascular, and hypertension treatment‐emergent adverse events (TEAEs) with bosutinib or imatinib for newly diagnosed chronic phase chronic myeloid leukemia were analyzed.Methods:Patients who received ≥1 dose of bosutinib (n = 268) or imatinib (n = 265) 400 mg/day in the phase 3 BFORE trial (NCT02130557) were included. Prespecified MedDRA terms comprised the clusters of investigator assessed TEAEs. Exposure‐adjusted TEAE rate was defined as the number of patients with TEAEs / total patient‐year, where patient‐year = the sum of total time to first TEAE for patients with TEAEs and treatment duration for patients without TEAEs.Results:After ≥36 months of follow‐up, 65% vs 62% of patients in the bosutinib vs imatinib arm were still on treatment. Rates of TEAEs, treatment withdrawals, and drug‐related TEAEs in the clusters of interest were low in both arms (Table). The most common cardiac, vascular, and hypertension TEAEs, respectively, were sinus bradycardia (2%), angina pectoris (3%), and hypertension (7%) vs prolonged QT (3%), peripheral coldness (1%), and hypertension (9%) with bosutinib vs imatinib; corresponding grade 3/4/5 TEAE rates in the respective clusters were 3%, 3%, and 4% vs 1%, 0.4%, and 4%. Hypertension was the only grade 3/4 TEAE occurring in ≥1% of patients in either arm (4% each); 1 grade 5 TEAE each was noted for bosutinib (cardiac failure) and imatinib (cerebrovascular accident). Exposure‐adjusted rates of cardiac, vascular, and hypertension TEAEs, respectively, were 0.04, 0.03, and 0.04 vs 0.03, 0.01, and 0.04 (grade 3/4/5 only: 0.01, 0.01, and 0.02 vs 0.01, 0.002, and 0.02) for bosutinib vs imatinib.Summary/Conclusion:Cardiac, vascular, and hypertension TEAE rates were similarly low with bosutinib and imatinib. A majority of TEAEs were low grade and few led to treatment withdrawal.image
PF607 MAINTENANCE WITH WEEKLY CARFILZOMIB IN ELDERLY NEWLY DIAGNOSED MULTIPLE MYELOMA (IFM 2012–03)
Authors: Bobin A. , Fouquet G. , Duhamel A. , Karlin L. , Kolb B. , Tiab M. , Bourquard P. , Lenain P. , Jaccard A. , Belhadj‐Merzoug K. , Attal M. , Moreau P. , Hulin C. , Facon T. , Avet‐Loiseau H. , Leleu X. 
Published: June 2019

Background:Continuous therapy, such as maintenance, appears to be a major therapeutic change in multiple myeloma, improving response rate and overall survival. Novel agents widen the range of treatment options, but still Lenalidomide (IMIiD) is widely used in this indication. Even though usually well tolerated it remains a daily treatment, and thus can lead to some side effects on a long term basis. Carfilzomib, a second generation PI, allows interesting response rate and prolonged survival, with manageable adverse events. Nevertheless, only few clinical trials focused on its use in maintenance rather than in first or second line treatment.Aims:Thereforewe, we chose to study maintenance Carfilzomib for elderly newly diagnosed multiple myeloma (eNDMM).Methods:IFM 2012–03 is a multicenter phase I study for eNDMM (patients aged 65 years old and more) that determined the maximal tolerated dose of weekly carfilzomib, associated with melphalan and prednisone (KMP), at 70 mg/m2. The following results will concern the second phase of the study using intravenous Carfilzomib monotherapy in maintenance. K was administered at 36 mg/m2 for 13 cycles on an every 2 weeks schedule.Results:Thirty eNDMM were recruited in IFM 2012–03. Median age is 75, with 56% R‐ISS 2 or 3 and 11% high‐risk cytogenetic. With K weekly from 36 to 70 mg/m2, OS is reported at 93.3%, including 46.7% ≥CR; median PFS is 35.8 months and median OS was not reached.Twenty‐two (73%) patients started K maintenance and 16 (73%) completed it. Four patients progressed and 2 stopped for AEs (renal amylosis, sensory neuropahty) during the maintenance phase. At maintenance completion, 50% were ≥CR. From the start of maintenance, in landmark analysis, median PFS is 28.1 months and the estimated 36‐months OS approximately 70%.Summary/Conclusion:Maintenance Carfilzomib enables deep responses as well as prolonged survival for patients over 65 years old presenting with a newly diagnosed multiple myeloma. With promising results, a fixed duration and a satisfying safety profile it could integrate new treatment strategies for ineligible to transplant NDMM. Surely patients could benefit of its efficacy in addition to simple administration modality. Further studies should still bring additional informations in order to confirm our results. Nowadays, multiple myeloma treatment landscape and clinical practice is constantly evolving leading to significant improvement for our patients.
PF619 LENALIDOMIDE IN COMBINATION WITH DEXAMETHASONE AS FIRST‐LINE THERAPY IN TRANSPLANT‐INELIGIBLE PATIENTS WITH MULTIPLE MYELOMA: INTERIM RESULTS OF THE OBSERVATIONAL STUDY FIRST‐NIS
Authors: Nückel H. , Hurtz H.‐J. , Schulz H. , Schulze M. , Koenigsmann M. , Dechow T. , Merling M. , Houet L. , Vannier C. , Potthoff K. 
Published: June 2019

Background:The lenalidomide‐dexamethasone (Rd) combination is a non‐alkylator‐based oral first‐line treatment option in transplant‐ineligible patients (pts) with multiple myeloma (MM). Approval of this regimen was based on the results of the pivotal phase III FIRST trial comparing Rd to the melphalan‐prednisone‐thalidomide (MPT) combination. Median OS was 10 months longer with Rd continuous versus MPT (Facon T et al., Blood 2018). Real‐world effectiveness and safety data of this commonly used first‐line treatment approach in the elderly population are still scarce.Aims:The focus of the first interim analysis is to evaluate baseline characteristics and early evidence for safety and effectiveness of first‐line Rd therapy documented in a real‐world patient population.Methods:The prospective, multicenter, non‐interventional, observational FIRST‐NIS study was designed to collect data on 167 pts with multiple myeloma receiving Rd as first‐line therapy from about 50 sites across Germany. Primary objective was to evaluate effectiveness of Rd assessed by 24‐month progression‐free survival (PFS) rate. Secondary endpoints included overall survival (OS), PFS, objective response rate (ORR), duration of response (DOR), quality of life (QoL) and safety. Descriptive statistics were used to analyze the data. The prespecified interim analysis was performed 24 months after the enrollment of the 50th patient.Results:At the cut‐off date of the interim analysis (July 3rd, 2018), 167 pts had been enrolled. Thereof, 155 pts qualified for effectiveness analysis and 159 pts for safety analysis. Baseline characteristics of all pts and of pts stratified by age (≤ 75 years, > 75 years) are presented (Table 1). The ORR was 53.5% in all pts, 60.9% in pts ≤ 75 years and 50.5% in pts > 75 years. 52.8% of pts developed grade 3/4 adverse events (AEs). Grade 3/4 AEs that occurred in at least 5% of pts were anemia (n = 9, 5.7%) and pneumonia (n = 8, 5.0%).Summary/Conclusion:The preliminary data of this interim analysis demonstrate a favorable risk‐benefit profile of Rd in the real‐world setting. Rd seems to be a reasonable first‐line treatment option that can also be provided to elderly pts > 75 years. The ORR results at this early analysis, however, are inferior compared to the outcomes of the pivotal phase III FIRST trial. One reason might be the high proportion of pts aged > 75 years in the FIRST‐NIS, i.e. 70% versus 35% in the FIRST trial. Results need to be confirmed in the final analysis.image
PF621 REAL WORLD EXPERIENCE IN THE MANAGEMENT OF WALDENSTRÖM'S MACROGLOBULINAEMIA FROM ANALYSIS OF THE RORY MORRISON REGISTRY
Authors: Bomsztyk J. , D'Sa S. , McCarthy H. , El‐Sharkawi D. , Scorer H. , Kothari J. , Pratt G. , Cuthill K. , Kyriakou C. 
Published: June 2019

Background:Waldenström's Macroglobulinaemia (WM) is characterised by the presence of an IgM paraprotein and bone marrow infiltration by lymphoplasmacytic lymphoma (Owen et al. 2003); patients present in a variable manner (Castillo et al 2016). A variety of treatments are used at front line and relapse. Current guidelines advocate chemoimmunotherapy in both settings (Owen et al. 2014). Novel agents are also effective spurred on by biological discoveries, including the somatic mutations in MYD88 and CXCR4 genes, but their precise role remains to be determined. Ibrutinib became available in the UK in 2017 via the Cancer Drugs Fund (CDF) for WM in the relapsed setting (NICE TA491).Aims:To describe the natural history of WM, monitor usage and impact of treatments including emerging therapies on outcomes in the UKMethods:The Rory Morrison Registry (RMR) collects data from existing and new patients with WM & related conditions from (so far) 14 centres across the UK using entry on to a web‐based platform. 701 patients are registered including 560 with a confirmed WM diagnosis. We describe treatment trends from across the UK at front line and first relapse. To facilitate analysis, we grouped the regimens.Results:383 patients have received front line therapy with at least 29 different regimens since 1984, and 215 second line therapy with at least 32 different regimens.The most common categories were DRC (90 patients; 23%), Alkylator based (75, 20%), R‐Bendamustine (50; 13%) and CHOP‐based (42; 11%), Other (37, 10%), Purine analogue (PA)‐based therapy (35; 9%), Rituximab monotherapy (R‐mono) (34, 9%), Bortezomib‐based (17; 4%) and BTK inhibitors (3, 1%).The use of each treatment has noticeably changed over time (See graph). The peak treatment choices in the early 2000 s were Alkylator‐ or CHOP‐based therapies. This has been superseded by DRC (since 2007) and R‐Bendamustine (since 2011). There has been a stable role for R‐mono and PA‐based therapy.Regimens used at first relapse have been highly variable till 2017 when Ibrutinib became available. Treatments from 209 patients at first relapse since 1984 show that the most common category was ‘Other’ (52; 25%), followed by BTK Inhibitors (41; 21%), R‐mono (including maintenance rituximab) (22; 11%), Alkylator‐based (21; 10%), PA‐based (19; 9%), DRC (19, 9%), Bendamustine‐based (17, 8%), CHOP‐based (13; 6%) and Bortezomib‐based (5; 2%). Notably, since 2017, of the 58 patients having 2ndline therapy 34 (58%) received BTK inhibitors.Summary/Conclusion:Observations from the Rory Morrison Registry demonstrate the evolving trends in WM treatment in the UK, including the emergence of DRC and R‐Bendamustine as standard frontline therapy and a preference for BTK inhibition as 2ndline therapy, since their availability. Further analysis is planned to assess the ‘real world’ impact of the emerging treatments.image