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

St. Anna Children‘s Hospital and Children’s Cancer Research Institute (CCRI), Department of Paediatrics, Medical University, 1090 Vienna, Austria
Children’s Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University, 1090 Vienna, Austria
Children and Adolescent Oncology Department, Gustave Roussy, Paris-Sud, University, 94805 Villejuif, France
Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain
Schneider Children‘s Medical Center of Israel, Sackler Faculty of Medicine Tel Aviv University, Petach, Tikvah 49202, Israel
University Hospital Ghent, 9000 Ghent, Belgium
Great Ormond Street Hospitalfor Children, WC1N 3JH London, UK
Institut Curie, 75248 Paris, France
Paediatric Haematology/Oncology, Our Lady’s Children’s Hospital, Crumlin, D12 N512 Dublin, Ireland
Sydney Children’s Hospital, Randwick NSW 2031, Australia
Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Hong Kong
Rikshospitalet, 0027 Oslo, Norway
Department of Paediatrics, University Hospital of Aarhus, 8200 Aarhus, Denmark
Department of Paediatrics, University Hospital Lausanne, 1011 Lausanne, Switzerland
AIT Austrian Institute of Technology GmbH, 8020 Graz, Austria
Apeiron Biologics AG, 1030 Vienna, Austria
St George's Hospital, Department Paediatric Surgery, SW17 0QT London, UK
National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, Department of Oncology, W1 2PG London, UK
IRCCS Istituto Giannina Gaslini, 16148 Genova, Italy
Institute of Cancer Research, Royal Marsden Hospital, SM5 2NG Sutton, UK
Department of Pediatric Hematology and Oncology, University Medicine Greifswald, 17489 Greifswald, Germany
Author to whom correspondence should be addressed.
The authors contributed equally to this work and share first authorship.
Cancers 2020, 12(2), 309;
Received: 23 December 2019 / Revised: 17 January 2020 / Accepted: 25 January 2020 / Published: 28 January 2020
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. View Full-Text
Keywords: high-risk neuroblastoma; immunotherapy; dinutuximab beta high-risk neuroblastoma; immunotherapy; dinutuximab beta
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MDPI and ACS Style

Ladenstein, R.; Pötschger, U.; Valteau-Couanet, D.; Luksch, R.; Castel, V.; Ash, S.; Laureys, G.; Brock, P.; Michon, J.M.; Owens, C.; Trahair, T.; Chi Fung Chan, G.; Ruud, E.; Schroeder, H.; Beck-Popovic, M.; Schreier, G.; Loibner, H.; Ambros, P.; Holmes, K.; Castellani, M.R.; Gaze, M.N.; Garaventa, A.; Pearson, A.D.J.; Lode, H.N. Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1). Cancers 2020, 12, 309.

AMA Style

Ladenstein R, Pötschger U, Valteau-Couanet D, Luksch R, Castel V, Ash S, Laureys G, Brock P, Michon JM, Owens C, Trahair T, Chi Fung Chan G, Ruud E, Schroeder H, Beck-Popovic M, Schreier G, Loibner H, Ambros P, Holmes K, Castellani MR, Gaze MN, Garaventa A, Pearson ADJ, Lode HN. Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1). Cancers. 2020; 12(2):309.

Chicago/Turabian Style

Ladenstein, Ruth, Ulrike Pötschger, Dominique Valteau-Couanet, Roberto Luksch, Victoria Castel, Shifra Ash, Genevieve Laureys, Penelope Brock, Jean Marie Michon, Cormac Owens, Toby Trahair, Godfrey Chi Fung Chan, Ellen Ruud, Henrik Schroeder, Maja Beck-Popovic, Guenter Schreier, Hans Loibner, Peter Ambros, Keith Holmes, Maria Rita Castellani, Mark N. Gaze, Alberto Garaventa, Andrew D.J. Pearson, and Holger N. Lode. 2020. "Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1)" Cancers 12, no. 2: 309.

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