Ladenstein, RuthPötschger, UlrikeValteau-Couanet, DominiqueLuksch, RobertoCastel, VictoriaAsh, ShifraLaureys, GenevieveBrock, PenelopeMichon, Jean MarieOwens, CormacTrahair, TobyChi Fung Chan, GodfreyRuud, EllenSchroeder, HenrikBeck-Popovic, MajaSchreier, GuenterLoibner, HansAmbros, PeterHolmes, KeithCastellani, Maria RitaGaze, Mark NGaraventa, AlbertoPearson, Andrew D JLode, Holger N2021-05-262021-05-262020-01-282072-66943201305510.3390/cancers12020309http://hdl.handle.net/10147/629474To 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.endinutuximab betahigh-risk neuroblastomaIMMUNOTHERAPYArticleCancers