PMID- 32013055 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210110 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 12 IP - 2 DP - 2020 Jan 28 TI - Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1). LID - 10.3390/cancers12020309 [doi] LID - 309 AB - 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. FAU - Ladenstein, Ruth AU - Ladenstein R AD - St. Anna Children's Hospital and Children's Cancer Research Institute (CCRI), Department of Paediatrics, Medical University, 1090 Vienna, Austria. FAU - Potschger, Ulrike AU - Potschger U AD - Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University, 1090 Vienna, Austria. FAU - Valteau-Couanet, Dominique AU - Valteau-Couanet D AD - Children and Adolescent Oncology Department, Gustave Roussy, Paris-Sud, University, 94805 Villejuif, France. FAU - Luksch, Roberto AU - Luksch R AD - Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. FAU - Castel, Victoria AU - Castel V AD - Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain. FAU - Ash, Shifra AU - Ash S AD - Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine Tel Aviv University, Petach, Tikvah 49202, Israel. FAU - Laureys, Genevieve AU - Laureys G AD - University Hospital Ghent, 9000 Ghent, Belgium. FAU - Brock, Penelope AU - Brock P AD - Great Ormond Street Hospitalfor Children, WC1N 3JH London, UK. FAU - Michon, Jean Marie AU - Michon JM AD - Institut Curie, 75248 Paris, France. FAU - Owens, Cormac AU - Owens C AD - Paediatric Haematology/Oncology, Our Lady's Children's Hospital, Crumlin, D12 N512 Dublin, Ireland. FAU - Trahair, Toby AU - Trahair T AD - Sydney Children's Hospital, Randwick NSW 2031, Australia. FAU - Chi Fung Chan, Godfrey AU - Chi Fung Chan G AD - Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Hong Kong. FAU - Ruud, Ellen AU - Ruud E AD - Rikshospitalet, 0027 Oslo, Norway. FAU - Schroeder, Henrik AU - Schroeder H AD - Department of Paediatrics, University Hospital of Aarhus, 8200 Aarhus, Denmark. FAU - Beck-Popovic, Maja AU - Beck-Popovic M AD - Department of Paediatrics, University Hospital Lausanne, 1011 Lausanne, Switzerland. FAU - Schreier, Guenter AU - Schreier G AD - AIT Austrian Institute of Technology GmbH, 8020 Graz, Austria. FAU - Loibner, Hans AU - Loibner H AD - Apeiron Biologics AG, 1030 Vienna, Austria. FAU - Ambros, Peter AU - Ambros P AD - Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University, 1090 Vienna, Austria. FAU - Holmes, Keith AU - Holmes K AD - St George's Hospital, Department Paediatric Surgery, SW17 0QT London, UK. FAU - Castellani, Maria Rita AU - Castellani MR AD - Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. FAU - Gaze, Mark N AU - Gaze MN AD - 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. FAU - Garaventa, Alberto AU - Garaventa A AD - IRCCS Istituto Giannina Gaslini, 16148 Genova, Italy. FAU - Pearson, Andrew D J AU - Pearson ADJ AD - Institute of Cancer Research, Royal Marsden Hospital, SM5 2NG Sutton, UK. FAU - Lode, Holger N AU - Lode HN AD - Department of Pediatric Hematology and Oncology, University Medicine Greifswald, 17489 Greifswald, Germany. LA - eng GR - 8177/CRUK_/Cancer Research UK/United Kingdom GR - n/a/Apeiron Biologics AG/ GR - n/a/Pierre Fabre Medicament/ GR - QLRI-CT-2002-01768/European Commission 5th Frame Work Grant/ PT - Journal Article DEP - 20200128 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC7072500 OTO - NOTNLM OT - dinutuximab beta OT - high-risk neuroblastoma OT - immunotherapy COIS- The academic data supported APEIRON to obtain the dinutuximab beta product licensure in May 2017 in the European Union (EMA). SIOPEN and CCRI established a contract with APEIRON regarding the provision of academic data. Ruth Ladenstein and Holger Lode acted as consultants for APEIRON on behalf of SIOPEN for the ch14.18/CHO development. The other authors declare no conflict of interest. EDAT- 2020/02/06 06:00 MHDA- 2020/02/06 06:01 PMCR- 2020/01/28 CRDT- 2020/02/05 06:00 PHST- 2019/12/23 00:00 [received] PHST- 2020/01/17 00:00 [revised] PHST- 2020/01/25 00:00 [accepted] PHST- 2020/02/05 06:00 [entrez] PHST- 2020/02/06 06:00 [pubmed] PHST- 2020/02/06 06:01 [medline] PHST- 2020/01/28 00:00 [pmc-release] AID - cancers12020309 [pii] AID - cancers-12-00309 [pii] AID - 10.3390/cancers12020309 [doi] PST - epublish SO - Cancers (Basel). 2020 Jan 28;12(2):309. doi: 10.3390/cancers12020309.