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

Autor: Ladenstein R; St. Anna Children's Hospital and Children's Cancer Research Institute (CCRI), Department of Paediatrics, Medical University, 1090 Vienna, Austria., Pötschger U; Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University, 1090 Vienna, Austria., Valteau-Couanet D; Children and Adolescent Oncology Department, Gustave Roussy, Paris-Sud, University, 94805 Villejuif, France., Luksch R; Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy., Castel V; Hospital Universitario y Politecnico La Fe, 46026 Valencia, Spain., Ash S; Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine Tel Aviv University, Petach, Tikvah 49202, Israel., Laureys G; University Hospital Ghent, 9000 Ghent, Belgium., Brock P; Great Ormond Street Hospitalfor Children, WC1N 3JH London, UK., Michon JM; Institut Curie, 75248 Paris, France., Owens C; Paediatric Haematology/Oncology, Our Lady's Children's Hospital, Crumlin, D12 N512 Dublin, Ireland., Trahair T; Sydney Children's Hospital, Randwick NSW 2031, Australia., Chi Fung Chan G; Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Hong Kong., Ruud E; Rikshospitalet, 0027 Oslo, Norway., Schroeder H; Department of Paediatrics, University Hospital of Aarhus, 8200 Aarhus, Denmark., Beck-Popovic M; Department of Paediatrics, University Hospital Lausanne, 1011 Lausanne, Switzerland., Schreier G; AIT Austrian Institute of Technology GmbH, 8020 Graz, Austria., Loibner H; Apeiron Biologics AG, 1030 Vienna, Austria., Ambros P; Children's Cancer Research Institute (CCRI), St. Anna Kinderkrebsforschung, Department of Paediatrics, Medical University, 1090 Vienna, Austria., Holmes K; St George's Hospital, Department Paediatric Surgery, SW17 0QT London, UK., Castellani MR; Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy., Gaze MN; 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., Garaventa A; IRCCS Istituto Giannina Gaslini, 16148 Genova, Italy., Pearson ADJ; Institute of Cancer Research, Royal Marsden Hospital, SM5 2NG Sutton, UK., Lode HN; Department of Pediatric Hematology and Oncology, University Medicine Greifswald, 17489 Greifswald, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2020 Jan 28; Vol. 12 (2). Date of Electronic Publication: 2020 Jan 28.
DOI: 10.3390/cancers12020309
Abstrakt: 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.
Competing Interests: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje