The added value of multi-state modelling in a randomized controlled trial : The HOVON 102 study re-analyzed
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Cancer medicine - 11(2022), 3 vom: 01. Feb., Seite 630-640 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bakunina, Katerina [VerfasserIn] |
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| Links: |
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| Themen: |
762RDY0Y2H |
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| Anmerkungen: |
Date Completed 18.04.2022 Date Revised 18.04.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cam4.4392 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM334889383 |
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| 520 | |a © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Koster, Eva A S |e verfasserin |4 aut | |
| 700 | 1 | |a van der Holt, Bronno |e verfasserin |4 aut | |
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| 700 | 1 | |a Breems, Dimitri A |e verfasserin |4 aut | |
| 700 | 1 | |a Gjertsen, Bjorn T |e verfasserin |4 aut | |
| 700 | 1 | |a Cloos, Jacqueline |e verfasserin |4 aut | |
| 700 | 1 | |a Valk, Peter J M |e verfasserin |4 aut | |
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| 700 | 1 | |a Cornelissen, Jan J |e verfasserin |4 aut | |
| 700 | 1 | |a de Wreede, Liesbeth C |e verfasserin |4 aut | |
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