Lode, Holger N., Siebert, Nikolai and Valteau-Couanet, Dominique , (2025) Fcγ receptor polymorphism in relapsed/refractory high-risk neuroblastoma patients correlates with outcomes in the SIOPEN dinutuximab beta long-term infusion trial. Clinical Cancer Research, 31 (17), 3692-3701. (doi:10.1158/1078-0432.CCR-25-0180).
Abstract
Purpose: to identify a tolerable dinutuximab beta long-term infusion (LTI) schedule with immunomodulatory activity for relapsed/refractory high-risk neuroblastoma.
Patients and methods: in this Phase I/II trial, dinutuximab beta LTI (five 35-day cycles) with subcutaneous interleukin-2 was evaluated in high-risk neuroblastoma cohorts (1x exploratory, 2x confirmatory). The composite primary endpoint was >80% patients free of intravenous morphine by day 5/cycle 1 plus ≥100 natural killer cells/μL and ≥1 μg/mL dinutuximab beta concentration by day 15/cycle 1. Secondary endpoints included objective response rate, event-free survival, overall survival, Fc-gamma receptor polymorphisms, and natural killer cells.
Results: overall, 122 patients were treated. At 10 mg/m2/day dinutuximab beta LTI, 95% patients (22/24 exploratory cohort; 20/20 confirmatory cohort 1) achieved the composite primary endpoint, with ≥80% patients intravenous morphine-free by day 5/cycle 1. End-of-treatment objective response rate was 45% in 78 evaluable patients. Two-year event-free survival and overall survival were 56% (±4%) and 73% (±4%) overall; and 45% (±5%) and 65% (±5%) in relapsed/refractory disease, respectively. Two-year survival rates were greater in patients with high-affinity Fc-gamma receptor polymorphisms and high-level natural killer cells versus patients with low-affinity Fc-gamma receptor polymorphisms and low-level natural killer cells (event-free survival, 79% [±9%] vs 35% [±11%], p=0.009; overall survival, 84% [±8%] vs 70% [±10%]; p=0.083). Multivariate analysis identified age >5 years, low-affinity Fc-gamma receptor polymorphisms, and relapse/refractory disease as independent risk factors.
Conclusion: dinutuximab beta LTI was well tolerated and clinically active in patients with relapsed/refractory high-risk neuroblastoma, with Fc-gamma receptor polymorphisms and natural killer cells identified as prognostic biomarkers.
More information
Identifiers
Catalogue record
Export record
Altmetrics
Contributors
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.