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

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Version: Final published version
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Serval ID
serval:BIB_BA95A00DDE07
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS.
Journal
Blood advances
Author(s)
Huls G., Chitu D.A., Pabst T., Klein S.K., Stussi G., Griskevicius L., Valk PJM, 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., van Marwijk Kooy R., Deeren D., van der Poel MWM, Legdeur M.C., Tick L., Chalandon Y., Ammatuna E., Blum S., Löwenberg B., Ossenkoppele G.J.
ISSN
2473-9537 (Electronic)
ISSN-L
2473-9529
Publication state
Published
Issued date
22/09/2020
Peer-reviewed
Oui
Volume
4
Number
18
Pages
4267-4277
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Pubmed
Web of science
Open Access
Yes
Create date
19/09/2020 13:10
Last modification date
07/11/2020 7:10
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