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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
Fcγ Receptor Polymorphism in Patients with Relapsed/Refractory High-Risk Neuroblastoma Correlates with Outcomes in
Holger N Lode1, Nikolai Siebert1, Dominique Valteau-Couanet2
1University Medicine Greifswald, Greifswald, Germany.
Purpose:
To identify a tolerable dinutuximab beta long-term infusion (LTI) schedule with immunomodulatory activity for relapsed/refractory high-risk neuroblastoma (HRNBL).
Patients And Methods:
In this phase I/II trial, dinutuximab beta LTI (five 35-day cycles) with subcutaneous interleukin-2 (IL-2) was evaluated in HRNBL cohorts (1× exploratory and 2× confirmatory). The composite primary endpoint was >80% patients free of intravenous morphine by day 5/cycle 1 plus ≥100 natural killer (NK) cells/μL and ≥1 μg/mL dinutuximab beta concentration by day 15/cycle 1. Secondary endpoints included objective response rate, event-free survival (EFS), overall survival (OS), Fcγ receptor (FCYR) polymorphisms, and NK cells.
Results:
Overall, 122 patients were treated. At 10 mg/m2/day dinutuximab beta LTI, 95% patients (22/24 exploratory cohort and 20/20 confirmatory cohort 1) achieved the composite primary endpoint, with ≥80% patients intravenous morphine-free by day 5/cycle 1. The end-of-treatment objective response rate was 45% in 78 evaluable patients. Two-year EFS and OS 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 FCYR polymorphisms and high-level NK cells versus patients with low-affinity FCYR polymorphisms and low-level NK cells [EFS, 79% (±9%) vs. 35% (±11%), P = 0.009; OS, 84% (±8%) vs. 70% (±10%); P = 0.083]. Multivariate analysis identified age >5 years, low-affinity FCYR polymorphisms, and relapse/refractory disease as independent risk factors.
Conclusions:
Dinutuximab beta LTI was well tolerated and clinically active in patients with relapsed/refractory HRNBL, with FCYR polymorphisms and NK cells identified as prognostic biomarkers.
