The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed
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 phas...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.4392 |
| _version_ | 1818082985978626048 |
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| author | Katerina Bakunina Hein Putter Jurjen Versluis Eva A. S. Koster Bronno van derHolt Markus G. Manz Dimitri A. Breems Bjorn T. Gjertsen Jacqueline Cloos Peter J. M. Valk Jakob Passweg Thomas Pabst Gert J. Ossenkoppele Bob Löwenberg Jan J. Cornelissen Liesbeth C. deWreede |
| author_facet | Katerina Bakunina Hein Putter Jurjen Versluis Eva A. S. Koster Bronno van derHolt Markus G. Manz Dimitri A. Breems Bjorn T. Gjertsen Jacqueline Cloos Peter J. M. Valk Jakob Passweg Thomas Pabst Gert J. Ossenkoppele Bob Löwenberg Jan J. Cornelissen Liesbeth C. deWreede |
| author_sort | Katerina Bakunina |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T19:30:48Z |
| format | Article |
| id | doaj.art-efddc38d4b904e3199e4f5412bc60ca2 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-10T19:30:48Z |
| publishDate | 2022-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-efddc38d4b904e3199e4f5412bc60ca22022-12-22T01:36:16ZengWileyCancer Medicine2045-76342022-02-0111363064010.1002/cam4.4392The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzedKaterina Bakunina0Hein Putter1Jurjen Versluis2Eva A. S. Koster3Bronno van derHolt4Markus G. Manz5Dimitri A. Breems6Bjorn T. Gjertsen7Jacqueline Cloos8Peter J. M. Valk9Jakob Passweg10Thomas Pabst11Gert J. Ossenkoppele12Bob Löwenberg13Jan J. Cornelissen14Liesbeth C. deWreede15Department of Hematology HOVON Data Center Erasmus MC Cancer Institute Rotterdam The NetherlandsDepartment of Biomedical Data Sciences Leiden University Medical Center Leiden The NetherlandsDepartment of Hematology Erasmus University Medical Center Cancer Institute Rotterdam The NetherlandsDepartment of Hematology Leiden University Medical Center Leiden The NetherlandsDepartment of Hematology HOVON Data Center Erasmus MC Cancer Institute Rotterdam The NetherlandsDepartment of Medical Oncology and Hematology University Hospital Zurich Zurich SwitzerlandDepartment of Hematology Hospital Network Antwerp Stuivenberg/Middelheim Antwerp BelgiumDepartment of Internal Medicine Hematology section Haukeland University Hospital Bergen NorwayDepartment of Hematology Amsterdam UMC VU University Medical Center Cancer Center Amsterdam Amsterdam The NetherlandsDepartment of Hematology Erasmus University Medical Center Cancer Institute Rotterdam The NetherlandsDepartment of Hematology University Hospital Basel Basel SwitzerlandDepartment of Medical Oncology University Hospital/Inselspital Bern SwitzerlandDepartment of Hematology Amsterdam UMC VU University Medical Center Cancer Center Amsterdam Amsterdam The NetherlandsDepartment of Hematology Erasmus University Medical Center Cancer Institute Rotterdam The NetherlandsDepartment of Hematology Erasmus University Medical Center Cancer Institute Rotterdam The NetherlandsDepartment of Biomedical Data Sciences Leiden University Medical Center Leiden The NetherlandsAbstract 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.https://doi.org/10.1002/cam4.4392AMLclofarabinecurrent leukemia‐free survivalHSCTmulti‐state modelRCT |
| spellingShingle | Katerina Bakunina Hein Putter Jurjen Versluis Eva A. S. Koster Bronno van derHolt Markus G. Manz Dimitri A. Breems Bjorn T. Gjertsen Jacqueline Cloos Peter J. M. Valk Jakob Passweg Thomas Pabst Gert J. Ossenkoppele Bob Löwenberg Jan J. Cornelissen Liesbeth C. deWreede The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed Cancer Medicine AML clofarabine current leukemia‐free survival HSCT multi‐state model RCT |
| title | The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed |
| title_full | The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed |
| title_fullStr | The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed |
| title_full_unstemmed | The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed |
| title_short | The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed |
| title_sort | added value of multi state modelling in a randomized controlled trial the hovon 102 study re analyzed |
| topic | AML clofarabine current leukemia‐free survival HSCT multi‐state model RCT |
| url | https://doi.org/10.1002/cam4.4392 |
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