دورية أكاديمية
أعرض في EDS

Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS.

التفاصيل البيبلوغرافية
العنوان: Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS.
المؤلفون: Huls G; Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands., Chitu DA; Department of Hematology, HOVON Data Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Pabst T; Department of Oncology, University Hospital, Inselspital, and University of Bern, Bern, Switzerland., Klein SK; Department of Hematology, Meander Hospital Amersfoort, Amersfoort, The Netherlands., Stussi G; Department of Hematology, Ospedale Regionale, Bellinzona, Switzerland., Griskevicius L; Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius University, Vilnius, Lithuania., Valk PJM; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands., Cloos J; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., van de Loosdrecht AA; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., Breems D; Department of Hematology, ZNA Stuivenberg/Middelheim, Antwerp, Belgium., van Lammeren-Venema D; Department of Hematology, Hagaziekenhuis, Den Haag, The Netherlands., van Zeventer I; Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands., Boersma R; Department of Hematology, Amphia Hospital, Breda, The Netherlands., Jongen-Lavrencic M; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands., Fehr M; Department of Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland., Hoogendoorn M; Department of Hematology, Medical Center Leeuwarden, Leeuwarden, The Netherlands., Manz MG; Department of Medical Oncology and Hematology, Universitätsspital Zurich, Zurich, Switzerland., Söhne M; Department of Hematology, Antonius Hospital, Nieuwegein, The Netherlands., van Marwijk Kooy R; Department of Hematology, Isala Hospital, Zwolle, The Netherlands., Deeren D; Department of Hematology, AZ Delta Roeselare, Roeselare, Belgium., van der Poel MWM; Department of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands., Legdeur MC; Department of Hematology, Medical Spectrum Twente, Enschede, The Netherlands., Tick L; Department of Hematology, Maxima Medical Center, Veldhoven, The Netherlands., Chalandon Y; Division of Hematology, University Hospital Genève and Faculty of Medicine, University of Genève, Genève, Switzerland; and., Ammatuna E; Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands., Blum S; Service and Central Laboratory of Hematology, Department of Oncology and Department of Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV), Lausanne, Switzerland., Löwenberg B; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands., Ossenkoppele GJ; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
المصدر: Blood advances [Blood Adv] 2020 Sep 22; Vol. 4 (18), pp. 4267-4277.
نوع المنشور: Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: Leukemia, Myeloid, Acute*/drug therapy , Myelodysplastic Syndromes*, Adenine/analogs & derivatives ; Decitabine/therapeutic use ; Humans ; Netherlands ; Piperidines
مستخلص: The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85.
(© 2020 by The American Society of Hematology.)
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المشرفين على المادة: 0 (Piperidines)
1X70OSD4VX (ibrutinib)
776B62CQ27 (Decitabine)
JAC85A2161 (Adenine)
تواريخ الأحداث: Date Created: 20200911 Date Completed: 20210514 Latest Revision: 20231104
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7509861
DOI: 10.1182/bloodadvances.2020002846
PMID: 32915972
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2020002846