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

• Main Authors: Ruth Ladenstein, 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, Holger N. Lode
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Cancers
• Subjects: high-risk neuroblastoma; immunotherapy; dinutuximab beta
• Online Access: https://www.mdpi.com/2072-6694/12/2/309

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&#8217; eligibility in the pre-immunotherapy analysis cohort. Median follow-up was 5.8 years (inter-quartile range (IQR): 4.2&#8722;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&#8722;47%) and 50% (46&#8722;55%) but was 57% (51&#8722;62%) and 64% (59&#8722;69%) for 378 patients receiving immunotherapy (<em>p</em> &lt; 0.001). A multivariate analysis identified absence of immunotherapy (p = 0.0002, hazard ratio (HR) 1.573); type of HDT (<em>p</em> = 0.0029, HR 1.431); less than complete response prior to maintenance therapy (<em>p</em> = 0.0043, HR 1.494) and &gt;1 metastatic compartment at diagnosis (<em>p</em> &lt; 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.