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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, Genevieve
; 
Brock, Penelope
; 
Michon, Jean Marie
; 
Owens, Cormac
... show 10 more
Authors
Ladenstein, Ruth
 Pötschger, Ulrike
 Valteau-Couanet, Dominique
 Luksch, Roberto
 Castel, Victoria
 Ash, Shifra
 Laureys, Genevieve
 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
Advisors
Editors
Other Contributors
Departments
Date
2020-01-28
Date Submitted
Keywords
dinutuximab beta
high-risk neuroblastoma
IMMUNOTHERAPY
Other Subjects
Subject Mesh
Planned Date
Start Date
Collaborators
Principal Investigators
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cancers-12-00309-v2.pdf
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URI
http://hdl.handle.net/10147/629474
Abstract
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.
Language
en
Citation
ISSN
2072-6694
eISSN
ISBN
DOI
10.3390/cancers12020309
PMID
32013055
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