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Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)

To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard ind...

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Autores principales: Ladenstein, Ruth, Pötschger, Ulrike, Valteau-Couanet, Dominique, Luksch, Roberto, Castel, Victoria, Ash, Shifra, Laureys, Geneviève, Brock, Penelope, Michon, Jean Marie, Owens, Cormac, Trahair, Toby, Chi Fung Chan, Godfrey, Ruud, Ellen, Schroeder, Henrik, Beck-Popovic, Maja, Schreier, Guenter, Loibner, Hans, Ambros, Peter, Holmes, Keith, Castellani, Maria Rita, Gaze, Mark N., Garaventa, Alberto, Pearson, Andrew D.J., Lode, Holger N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072500/
https://www.ncbi.nlm.nih.gov/pubmed/32013055
http://dx.doi.org/10.3390/cancers12020309
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author Ladenstein, Ruth
Pötschger, Ulrike
Valteau-Couanet, Dominique
Luksch, Roberto
Castel, Victoria
Ash, Shifra
Laureys, Geneviève
Brock, Penelope
Michon, Jean Marie
Owens, Cormac
Trahair, Toby
Chi Fung Chan, Godfrey
Ruud, Ellen
Schroeder, Henrik
Beck-Popovic, Maja
Schreier, Guenter
Loibner, Hans
Ambros, Peter
Holmes, Keith
Castellani, Maria Rita
Gaze, Mark N.
Garaventa, Alberto
Pearson, Andrew D.J.
Lode, Holger N.
author_facet Ladenstein, Ruth
Pötschger, Ulrike
Valteau-Couanet, Dominique
Luksch, Roberto
Castel, Victoria
Ash, Shifra
Laureys, Geneviève
Brock, Penelope
Michon, Jean Marie
Owens, Cormac
Trahair, Toby
Chi Fung Chan, Godfrey
Ruud, Ellen
Schroeder, Henrik
Beck-Popovic, Maja
Schreier, Guenter
Loibner, Hans
Ambros, Peter
Holmes, Keith
Castellani, Maria Rita
Gaze, Mark N.
Garaventa, Alberto
Pearson, Andrew D.J.
Lode, Holger N.
author_sort Ladenstein, Ruth
collection PubMed
description To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepoint of 109 days, resulting from the median time between ASCR and initiation of immunotherapy, was used to define patients’ eligibility in the pre-immunotherapy analysis cohort. Median follow-up was 5.8 years (inter-quartile range (IQR): 4.2–8.2 years) for 844 eligible patients balanced for risk factors, such as age, sex, stage 4, MYCN amplification and response prior to HDT. The five-year event-free and overall survival (95% confidence interval (CI) of 466 patients not receiving immunotherapy was 42% (38–47%) and 50% (46–55%) but was 57% (51–62%) and 64% (59–69%) for 378 patients receiving immunotherapy (p < 0.001). A multivariate analysis identified absence of immunotherapy (p = 0.0002, hazard ratio (HR) 1.573); type of HDT (p = 0.0029, HR 1.431); less than complete response prior to maintenance therapy (p = 0.0043, HR 1.494) and >1 metastatic compartment at diagnosis (p < 0.001, HR 2.665) as risk factors for relapse or progression. Results suggest an important role for dinutuximab beta-based immunotherapy within the treatment concepts applied in HR-NBL1/SIOPEN.
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spelling pubmed-70725002020-03-19 Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1) Ladenstein, Ruth Pötschger, Ulrike Valteau-Couanet, Dominique Luksch, Roberto Castel, Victoria Ash, Shifra Laureys, Geneviève Brock, Penelope Michon, Jean Marie Owens, Cormac Trahair, Toby Chi Fung Chan, Godfrey Ruud, Ellen Schroeder, Henrik Beck-Popovic, Maja Schreier, Guenter Loibner, Hans Ambros, Peter Holmes, Keith Castellani, Maria Rita Gaze, Mark N. Garaventa, Alberto Pearson, Andrew D.J. Lode, Holger N. Cancers (Basel) Article To explore the effects of immunotherapy in the International Society of Paediatric Oncology Europe Neuroblastoma Group SIOPEN high-risk neuroblastoma 1 trial (HR-NBL1 trial), two cohorts were studied: one prior to and one after the introduction of dinutuximab beta. All patients received standard induction and high-dose therapy (HDT) with autologous stem cell rescue (ASCR); the local control comprised surgery and radiotherapy to the primary tumour site, followed by isotretinoin. A landmark timepoint of 109 days, resulting from the median time between ASCR and initiation of immunotherapy, was used to define patients’ eligibility in the pre-immunotherapy analysis cohort. Median follow-up was 5.8 years (inter-quartile range (IQR): 4.2–8.2 years) for 844 eligible patients balanced for risk factors, such as age, sex, stage 4, MYCN amplification and response prior to HDT. The five-year event-free and overall survival (95% confidence interval (CI) of 466 patients not receiving immunotherapy was 42% (38–47%) and 50% (46–55%) but was 57% (51–62%) and 64% (59–69%) for 378 patients receiving immunotherapy (p < 0.001). A multivariate analysis identified absence of immunotherapy (p = 0.0002, hazard ratio (HR) 1.573); type of HDT (p = 0.0029, HR 1.431); less than complete response prior to maintenance therapy (p = 0.0043, HR 1.494) and >1 metastatic compartment at diagnosis (p < 0.001, HR 2.665) as risk factors for relapse or progression. Results suggest an important role for dinutuximab beta-based immunotherapy within the treatment concepts applied in HR-NBL1/SIOPEN. MDPI 2020-01-28 /pmc/articles/PMC7072500/ /pubmed/32013055 http://dx.doi.org/10.3390/cancers12020309 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ladenstein, Ruth
Pötschger, Ulrike
Valteau-Couanet, Dominique
Luksch, Roberto
Castel, Victoria
Ash, Shifra
Laureys, Geneviève
Brock, Penelope
Michon, Jean Marie
Owens, Cormac
Trahair, Toby
Chi Fung Chan, Godfrey
Ruud, Ellen
Schroeder, Henrik
Beck-Popovic, Maja
Schreier, Guenter
Loibner, Hans
Ambros, Peter
Holmes, Keith
Castellani, Maria Rita
Gaze, Mark N.
Garaventa, Alberto
Pearson, Andrew D.J.
Lode, Holger N.
Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)
title Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)
title_full Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)
title_fullStr Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)
title_full_unstemmed Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)
title_short Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)
title_sort investigation of the role of dinutuximab beta-based immunotherapy in the siopen high-risk neuroblastoma 1 trial (hr-nbl1)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072500/
https://www.ncbi.nlm.nih.gov/pubmed/32013055
http://dx.doi.org/10.3390/cancers12020309
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