1. Inicio
  2. Publicaciones
  3. Fc? Receptor Polymorphism in Patients with Relapsed/Refractory High-Risk Neuroblastoma Correlates with Outcomes in the SIOPEN Dinutuximab Beta Long-Term Infusion Trial

Fc? Receptor Polymorphism in Patients with Relapsed/Refractory High-Risk Neuroblastoma Correlates with Outcomes in the SIOPEN Dinutuximab Beta Long-Term Infusion Trial

Fecha de publicación:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Lode H.N.
  • Siebert N.
  • Valteau-Couanet D.
  • Garaventa A.
  • Anderson J.
  • Yaniv I.
  • Ash S.
  • Gray J.
  • Klingebiel T.
  • Loibner H.
  • Luksch R.
  • Manzitti C.
  • Michon J.M.
  • Owens C.
  • Pötschger U.
  • Troschke-Meurer S.
  • Glogova E.
  • Ladenstein R.

Grupos

Abstract

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 end-points included objective response rate, event-free survival (EFS), overall survival (OS), Fc? receptor (FCYR) polymor-phisms, 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 lowaffinity FCYR polymorphisms and low-level NK cells [EFS, 79% (±9%) vs. 35% (±11%), P ¼ 0.009; OS, 84% (±8%) vs. 70% (±10%); P ¼ 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. © 2025 The Authors; Published by the American Association for Cancer Research.

Datos de la publicación

ISSN/ISSNe:
1078-0432, 1557-3265

CLINICAL CANCER RESEARCH  AMER ASSOC CANCER RESEARCH

Tipo:
Article
Páginas:
3692-3701
PubMed:
40627545
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
4,399 SCImago ℠
Cuartil:
Q1 SCImago ℠

Documentos

  • No hay documentos

Métricas

Filiaciones mostrar / ocultar

Keywords

  • Adolescent; Adult; Antibodies, Monoclonal; Child; Child, Preschool; Drug Resistance, Neoplasm; Female; Humans; Infant; Interleukin-2; Killer Cells, Natural; Male; Neoplasm Recurrence, Local; Neuroblastoma; Polymorphism, Genetic; Prognosis; Receptors, IgG; Treatment Outcome; Young Adult; creatinine; dinutuximab; Fc receptor; gamma glutamyltransferase; interleukin 2; isotretinoin; morphine; dinutuximab; interleukin 2; monoclonal antibody; anaphylaxis; anorexia; Article; cancer survival; capillary leak syndrome; child; Common Terminology Criteria for Adverse Events; computer assisted tomography; constipation; cytokine release syndrome; diarrhea; disease exacerbation; drug response; drug toxicity; drug withdrawal; edema; enzyme linked immunosorbent assay; event free survival; fatigue; female; fever; headache; hematologic disease; hematuria; high risk neuroblastoma; human; hypertension; hypotension; immunotherapy; infection; liver toxicity; lung toxicity; major clinical study; male; mood ch

Cita

Compartir