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  • 1
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 61, No. 6 ( 2020-05-11), p. 1435-1444
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
    detail.hit.zdb_id: 2030637-4
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  • 2
    In: European Journal of Haematology, Wiley, Vol. 105, No. 5 ( 2020-11), p. 646-654
    Abstract: Ibrutinib has now been approved for treatment of chronic lymphocytic leukemia (CLL) in both front‐line setting and as later‐line treatment. However, knowledge about the outcomes and adverse events (AE) among patients at a population‐based level is still limited. Objectives To report outcomes and AEs in a population‐based cohort treated with ibrutinib outside clinical trials. Methods We conducted a multicenter, retrospective cohort study including all patients with CLL treated with ibrutinib. Results In total, 205 patients were included of whom 39 (19%) were treatment‐naïve. The median follow‐up was 21.4 months (interquartile range (IQR), 11.9,32.8), the estimated overall survival at 12 months was 88.8% (95% confidence interval (CI); 84.3%, 93.3%), and the estimated progression‐free survival at 12 months was 86.3% (95% CI; 81.3%, 91.2%). During follow‐up, 200 (97.6%) patients had at least one AE and 100 (48.8%) patients had at least one grade ≥3 AE. Eighty‐six patients (42.0%) discontinued ibrutinib, hereof 47 (54.7%) due to AEs and 19 (22.1%) had progression of CLL or Richter transformation. Conclusions In our study, we find comparable, though slightly inferior, overall, and progression‐free survival, and discontinuation due to toxicity was higher compared with clinical trials. Patient training and information may improve treatment adherence outside clinical trials.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2027114-1
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  • 3
    Online Resource
    Online Resource
    American Meteorological Society ; 1989
    In:  Journal of the Atmospheric Sciences Vol. 46, No. 12 ( 1989-06), p. 1664-1686
    In: Journal of the Atmospheric Sciences, American Meteorological Society, Vol. 46, No. 12 ( 1989-06), p. 1664-1686
    Type of Medium: Online Resource
    ISSN: 0022-4928 , 1520-0469
    RVK:
    Language: English
    Publisher: American Meteorological Society
    Publication Date: 1989
    detail.hit.zdb_id: 218351-1
    detail.hit.zdb_id: 2025890-2
    SSG: 16,13
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  • 4
    Online Resource
    Online Resource
    Common Ground Research Networks ; 2011
    In:  The International Journal of Climate Change: Impacts and Responses Vol. 2, No. 3 ( 2011), p. 143-162
    In: The International Journal of Climate Change: Impacts and Responses, Common Ground Research Networks, Vol. 2, No. 3 ( 2011), p. 143-162
    Type of Medium: Online Resource
    ISSN: 1835-7156
    URL: Issue
    Language: Unknown
    Publisher: Common Ground Research Networks
    Publication Date: 2011
    detail.hit.zdb_id: 2645930-9
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  • 5
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1849-1849
    Abstract: Background : The UK Myeloma Research Alliance recently introduced a new clinical prediction model for outcome in newly diagnosed multiple myeloma (MM) patients not eligible for autologous hematopoietic stem-cell transplantation (ASCT) (Lancet Haematology 2019; 6: e154-66). The score or Myeloma Risk Profile, MRP, includes WHO performance status (PS), the International Staging System (ISS), age, and C-reactive protein (CRP) as prognostic variables. First a score is calculated by the formula: Score = (PS - 2) * 0.199 + (age - 74.4) * 0.0165 + (ISS - 2) * 0.212 + (log(CRP + 1) - 2.08) * 0.0315, where PS and ISS are defined as numbers between 0-4 and 1-3, respectively, and CRP is in mg/L. Next, three risk groups are defined as 1) low risk: score 〈 -0.256, 2) medium risk: -0.256 ≤ score ≤ -0.0283, or 3) high risk: score 〉 -0.0283. The MRP score was generated based on two prospective clinical trial cohorts, the NRCI-Myeloma XI study (ISRCTN49407852) as training set or internal validation, and the NRCI-Myeloma IX study (Blood 2011; 118, 1231-38) as test set or external validation. Both trials investigated conventional oral alkylating agents, cyclophosphamide or melphalan, in combination with thalidomide, lenalidomide, and/or bortezomib; thus including drugs typically used in treatment of elderly MM patients. Establishment of the model included 1852 patients in the training set, and 520 patients in the test set. All patients were recruited as part of clinical trials and therefore fulfilled defined inclusion and exclusion criteria. To validate the MRP score in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients in the Danish National MM Registry. Methods : The Danish MM registry started 01 January 2005. It includes registration of all diagnosed MM patients in Denmark and given first- and second-line treatment. A data validation study has been performed (J Clin Epidemiology, 2016; 8: 583-587). At 31 December 2014, 2,926 newly diagnosed treatment demanding MM patients were registered, hereof 1,803 patients were above 65 years and found ineligible for ASCT, and constituted the patient population for this study. Results: Of 1,803 transplant in-eligible but treatment demanding newly diagnosed MM patients above 65 years 426 patients had one or more missing values for calculation of the MRP score, most often this was caused by missing ISS. Thus, 1,377 patients were evaluable with a median follow-up of 40.9 months. Patients were treated according to standard of care in Denmark during the 10-years registration period which included upfront conventional alkylating agent, mostly melphalan in 37.7%, thalidomide-based in 25.6%, bortezomib-based in 26.1%, lenalidomide based in 2.7%, and only palliative, mostly steroid-based in 7.9%. The distribution of the risk groups according to MRP was as follows: low risk 28.5%, medium-risk 25.1%, and high-risk 46.4%. Ccompared to the UK datasets we had a higher proportion of high-risk patients which undoubtedly reflects that our cohort is population based. Median survivals for the 3 risk groups are presented in Table 1 and overall survival curves illustrated in Figure 1. The model performed well in separating the patients into subgroups with different survival risks. In conclusion, our real life population-based data confirm that the MRP score is a robust and valuable risk assessment tool for elderly newly diagnosed MM patients older than 65 and not eligible for ASCT. An important advantage of the MRP score is that it is calculated from simple parameters that should be part of everyday diagnostic work-up. Disclosures Vangsted: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Jansen: Honoraria. Plesner:Takeda: Consultancy; Oncopeptides: Consultancy; Genmab: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Janssen: Consultancy, Research Funding. Frederiksen:Novartis: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Alexion: Research Funding; Abbvie: Research Funding. Abildgaard:Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
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  • 6
    In: Quality of Life Research, Springer Science and Business Media LLC, Vol. 29, No. 2 ( 2020-02), p. 335-346
    Abstract: The quality of patient-reported outcome (PRO) data can be compromised by non-response (NR) to scheduled questionnaires, particularly if reasons for NR are related to health problems, which may lead to unintended bias. The aim was to investigate whether electronic reminders and real-time monitoring improve PRO completion rate. Methods The population-based study “Quality of life in Danish multiple myeloma patients” is a longitudinal, multicentre study with consecutive inclusion of treatment-demanding newly diagnosed or relapsed patients with multiple myeloma. Education of study nurses in the avoidance of NR, electronic reminders, 7-day response windows and real-time monitoring of NR were integrated in the study. Patients complete PRO assessments at study entry and at 12 follow-up time points using electronic or paper questionnaires. The effect of the electronic reminders and real-time monitoring were investigated by comparison of proportions of completed questionnaires before and after each intervention. Results The first 271 included patients were analysed; of those, 249 (85%) chose electronic questionnaires. Eighty-four percent of the 1441 scheduled PRO assessments were completed within the 7-day response window and 11% after real-time monitoring, achieving a final PRO completion rate of 95%. A significant higher proportion of uncompleted questionnaires were completed after the patients had received the electronic reminder and after real-time monitoring. Conclusions Electronic reminders and real-time monitoring contributed to a very high completion rate in the study. To increase the quality of PRO data, we propose integrating these strategies in PRO studies, however highlighting that an increase in staff resources is required for implementation.
    Type of Medium: Online Resource
    ISSN: 0962-9343 , 1573-2649
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2008960-0
    SSG: 5,1
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  • 7
    In: COVID, MDPI AG, Vol. 1, No. 1 ( 2021-08-27), p. 303-314
    Abstract: In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic.
    Type of Medium: Online Resource
    ISSN: 2673-8112
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 3056217-X
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  • 8
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1767-1767
    Abstract: Introduction Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase for treatment of chronic lymphocytic leukemia (CLL). Ibrutinib has demonstrated superior efficacy for patients with TP53 aberration or relapsed/refractory (R/R) CLL; and more recently superior progression free survival (PFS) has been demonstrated compared to chemoimmunotherapy as first line therapy. However, knowledge about the outcomes and adverse events (AE) upon ibrutinib among patients at a population-based level are still limited. The aim of the here presented study is to explore outcomes of ibrutinib treatment in a population-based cohort of patients with CLL treated with ibrutinib in Denmark. Methods In this retrospective study, patients from 8 hospitals in Denmark, who were diagnosed with CLL and treated with ibrutinib from April 2014 until February 2019 were included. Medical records were retrospectively reviewed to obtain information. Patients receiving ibrutinib within clinical trials were excluded. Overall survival (OS) was defined as time from ibrutinib start to death from any cause while PFS was defined as time from ibrutinib start to progression or death from any cause. PFS and OS were analyzed with the Kaplan-Meier method while cumulative incidence was calculated with the Aalen-Johansen estimator. Results In total, 205 patients with CLL receiving ibrutinib treatment were identified from hospital records and registries. The median follow-up was 21.4 months (IQR, 11.9-32.8) and the median time on ibrutinib was 16.8 months (IQR, 6.0-28.1). The median age at treatment initiation was 72.8 years (IQR, 65.7-77.8), 128 (62.4%) were male, and 111 (63.4%) were Binet stage B/C at treatment initiation out of 175 with available information regarding clinical stage. Thirty-nine (19.0%) received ibrutinib as first-line, and 166 for R/R CLL with a median of 2 (range, 1-8) prior treatment regimens. Information on TP53 aberration was available for 149 and regarding IGHV mutation for 147 patients, 111 (74.5%) had TP53 aberration and 107 (72.8%) were IGHV unmutated. Eighty-six patients (42.0%) discontinued ibrutinib during follow-up with a median time until discontinuation of 9.3 months (IQR, 3.0-23.2). Forty-seven (54.7%) discontinued due to AEs, 19 (22.1%) due to progression (12 had progression of CLL and 7 had Richter's transformation) while the remaining 20 (23.2%) discontinued due to other reasons. The estimated cumulative incidence of discontinuation at 12 months was 24.8% (95% CI: 18.6-30.9). The estimated OS after 12 and 24 months was 88.8% (95%CI: 84.3-93.3) and 76.8% (95%CI: 70.4-83.2) and the estimated PFS after 12 and 24 months was 87.3% (95%CI: 82.5-92.1) and 72.4% (95%CI: 65.5-79.2). One hundred and eighty-eight (91.7%) experienced at least one AE, among these 45 (23.9%) experienced a grade 3+. The most common AEs were hemorrhage (tendency to bruise, epistaxis etc.) which occurred in 86 (42.0%) of all and musculoskeletal and connective tissue disorders (arthralgia, myalgia etc.) which occurred in 82 (40.0%). Thirty-one (15.1%) patients experienced atrial fibrillation while on ibrutinib and 14 (6.8%) developed hypertension. One hundred and thirty-seven patients (66.8%) had at least one infection and among these 80 (58.4%) were hospitalized with an infection. The most common infections were lower respiratory tract infections and urinary tract infections that occurred for 88 (42.9%) and 41 (20.0%). The estimated cumulative incidence for any infection was 58.9% (95%CI: 52.0-65.9) at 12 months. Conclusion This is the first study describing outcomes for a population-based cohort of CLL patients treated with ibrutinib in Denmark. Real-world studies are warranted, to confirm the results from clinical trials. In this study, patients appear to have comparable OS and types of AE compared with the RESONATE trial. Differences in frequency of AEs compared to the clinical trial may reflect the focus of clinicians in routine practice. Discontinuation in this cohort was higher compared to clinical trials but comparable to previously reported real-world studies. While ibrutinib can be safely managed in routine clinical practice, this study demonstrates that a quarter of patients discontinue treatment due to mainly AEs. Further patient training and information, and in some instances personalized treatment with other targeted agents based on adverse event profile, may improve treatment adherence. Disclosures Aarup: Research Committee, Rigshospitalet: Research Funding. Enggaard:Abbie: Other: Advisory board; Gilead: Other: Advisory board; Janssen: Other: Advisory board. Frederiksen:Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding; Alexion: Research Funding. Niemann:Novo Nordisk Foundation: Research Funding; AstraZeneca: Consultancy, Other: Travel Grant, Research Funding; Sunesis: Consultancy; Acerta: Consultancy; CSL Behring: Consultancy; Roche: Other: Travel Grant; Janssen: Consultancy, Other: Travel Grant, Research Funding; Gilead: Other: Travel Grant; Abbvie: Consultancy, Other: Travel Grant, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    American Meteorological Society ; 1996
    In:  Journal of the Atmospheric Sciences Vol. 53, No. 10 ( 1996-05), p. 1410-1432
    In: Journal of the Atmospheric Sciences, American Meteorological Society, Vol. 53, No. 10 ( 1996-05), p. 1410-1432
    Type of Medium: Online Resource
    ISSN: 0022-4928 , 1520-0469
    RVK:
    Language: English
    Publisher: American Meteorological Society
    Publication Date: 1996
    detail.hit.zdb_id: 218351-1
    detail.hit.zdb_id: 2025890-2
    SSG: 16,13
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  • 10
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2017
    In:  Climate Dynamics Vol. 48, No. 9-10 ( 2017-5), p. 3261-3282
    In: Climate Dynamics, Springer Science and Business Media LLC, Vol. 48, No. 9-10 ( 2017-5), p. 3261-3282
    Type of Medium: Online Resource
    ISSN: 0930-7575 , 1432-0894
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 382992-3
    detail.hit.zdb_id: 1471747-5
    SSG: 16,13
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