dc.contributor.author | Bakunina, Katerina | |
dc.contributor.author | Putter, Hein | |
dc.contributor.author | Versluis, Jurjen | |
dc.contributor.author | Koster, Eva A. S. | |
dc.contributor.author | van der Holt, Bronno | |
dc.contributor.author | Manz, Markus G. | |
dc.contributor.author | Breems, Dimitri A. | |
dc.contributor.author | Gjertsen, Bjørn Tore | |
dc.contributor.author | Cloos, Jacqueline | |
dc.contributor.author | Valk, Peter J. M. | |
dc.contributor.author | Passweg, Jakob | |
dc.contributor.author | Pabst, Thomas | |
dc.contributor.author | Ossenkoppele, Gert J. | |
dc.contributor.author | Löwenberg, Bob | |
dc.contributor.author | Cornelissen, Jan J. | |
dc.contributor.author | de Wreede, Liesbeth C. | |
dc.date.accessioned | 2022-04-21T08:02:46Z | |
dc.date.available | 2022-04-21T08:02:46Z | |
dc.date.created | 2022-01-05T20:41:07Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 2045-7634 | |
dc.identifier.uri | https://hdl.handle.net/11250/2991824 | |
dc.description.abstract | Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re-analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomized between standard induction chemotherapy with or without clofarabine. Using multi-state models, we evaluated the effects of induction chemotherapy outcomes (complete remission [CR], measurable residual disease [MRD]), and post-remission therapy with allogeneic stem cell transplantation [alloSCT] on relapse and death. Through the latter a consistent reduction in the hazard of relapse in the clofarabine arm compared to the standard arm was found, which occurred irrespective of MRD status or post-remission treatment with alloSCT, demonstrating a strong and persistent antileukemic effect of clofarabine. During the time period between achieving CR and possible post-remission treatment with alloSCT, non-relapse mortality was higher in patients receiving clofarabine. An overall net benefit of treatment with clofarabine was identified using the composite endpoint current leukemia-free survival (CLFS). In conclusion, these results enforce and extend the earlier reported beneficial effect of clofarabine in AML and show that multi-state models further detail the effect of treatment on competing and series of events. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Wiley | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | The added value of multi-state modelling in a randomized controlled trial: The HOVON 102 study re-analyzed | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2021 The Author(s) | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.1002/cam4.4392 | |
dc.identifier.cristin | 1975501 | |
dc.source.journal | Cancer Medicine | en_US |
dc.source.pagenumber | 630-640 | en_US |
dc.identifier.citation | Cancer Medicine. 2022, 11 (3), 630-640. | en_US |
dc.source.volume | 11 | en_US |
dc.source.issue | 3 | en_US |