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: Peter J. M. Valk, Yves Chalandon, Thomas Pabst, Markus G. Manz, Dimitri Breems, Maaike Sohne, Bob Löwenberg, Emanuele Ammatuna, Marjolein van der Poel, Sabine Blum, Dries Deeren, Rien van Marwijk Kooy, Dana A. Chitu, Mojca Jongen-Lavrencic, Lidwine W. Tick, Marie Cecile J.C. Legdeur, Gerwin Huls, Saskia K. Klein, Danielle van Lammeren-Venema, Gert J. Ossenkoppele, Georg Stussi, Arjan A. van de Loosdrecht, Isabelle A van Zeventer, Rinske S. Boersma, M. Fehr, Mels Hoogendoorn, Jacqueline Cloos, Laimonas Griskevicius
المساهمون: Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Hematology laboratory, CCA - Cancer Treatment and quality of life, Hematology, University of Zurich, Huls, Gerwin, Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
المصدر: Blood advances, vol. 4, no. 18, pp. 4267-4277
Blood Advances, Vol. 4, No 18 (2020) pp. 4267-4277
Blood, 4(18), 4267-4277. AMER SOC HEMATOLOGY
Blood, 4(18), 4267-4277. American Society of Hematology
Blood advances, 4(18), 4267-4277. American Society of Hematology
Huls, G, Chitu, D A, Pabst, T, Klein, S K, Stussi, G, Griskevicius, L, Valk, P J M, Cloos, J, van de Loosdrecht, A A, Breems, D, van Lammeren-Venema, D, van Zeventer, I, Boersma, R, Jongen-Lavrencic, M, Fehr, M, Hoogendoorn, M, Manz, M G, Söhne, M, Kooy, R V M, Deeren, D, van der Poel, M W M, Legdeur, M C, Tick, L, Chalandon, Y, Ammatuna, E, Blum, S, Löwenberg, B & Ossenkoppele, G J 2020, ' Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS ', Blood, vol. 4, no. 18, pp. 4267-4277 . https://doi.org/10.1182/BLOODADVANCES.2020002846
Blood advances, 4(18), 4267-4277. The American Society of Hematology
Blood Adv
سنة النشر: 2020
مصطلحات موضوعية: Oncology, medicine.medical_specialty, Clinical Trials and Observations, medicine.medical_treatment, 2720 Hematology, Decitabine, MINIMAL RESIDUAL DISEASE, 610 Medicine & health, Hematopoietic stem cell transplantation, ACUTE MYELOID-LEUKEMIA, chemistry.chemical_compound, Piperidines, Internal medicine, CONVENTIONAL CARE REGIMENS, AZACITIDINE THERAPY, Humans, Medicine, Adverse effect, TREATMENT RESPONSE, Netherlands, MYELODYSPLASTIC SYNDROME, ddc:616, business.industry, Adenine, CLINICAL-RESPONSE, Myeloid leukemia, Hematology, Minimal residual disease, Transplantation, Leukemia, Myeloid, Acute, chemistry, Tolerability, HYPOMETHYLATING AGENT THERAPY, Myelodysplastic Syndromes, Ibrutinib, 10032 Clinic for Oncology and Hematology, SURVIVAL, TRIAL, business, medicine.drug
الوصف: 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.
وصف الملف: application/pdf; advancesadv2020002846.pdf - application/pdf
اللغة: English
تدمد: 2473-9529
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f035f8641df261cae7346abf960dbaaf
https://serval.unil.ch/notice/serval:BIB_BA95A00DDE07
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....f035f8641df261cae7346abf960dbaaf
قاعدة البيانات: OpenAIRE
الوصف
تدمد:24739529