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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7072500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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