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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...

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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
Descripción
Sumario: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.