Chemo-immunotherapy with dinutuximab beta in patients with relapsed/progressive high-risk neuroblastoma: does chemotherapy backbone matter?

Chemotherapy Dinutuximab beta Immunotherapy Neuroblastoma Real-world data Relapse

Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
May 2024
Historique:
received: 16 01 2024
revised: 27 02 2024
accepted: 28 02 2024
pubmed: 16 3 2024
medline: 16 3 2024
entrez: 15 3 2024
Statut: ppublish

Résumé

Addition of anti-GD2 antibodies to temozolomide-based chemotherapy has demonstrated increased antitumor activity and progression-free survival in patients with relapsed/progressive high-risk neuroblastoma. However, chemo-immunotherapy is not yet approved for this indication. This study presents the chemo-immunotherapy experience in patients with relapsed/progressive high-risk neuroblastoma treated within the off-label use program of the Neuroblastoma Committee of the French Society of Pediatric Oncology (SFCE). Dinutuximab beta (dB) was administered alongside temozolomide-topotecan (TOTEM) or temozolomide-irinotecan (TEMIRI) at first disease relapse/progression or topotecan-cyclophosphamide (TopoCyclo) at further relapse/progression. Real-world data on demographics, treatment, antitumor activity and safety was collected from all patients after inclusion in SACHA-France (NCT04477681), a prospective national registry, which documents safety and efficacy data on innovative anticancer therapies prescribed to patients ≤ 25 years old as compassionate or off-label use. Between February 2021 and July 2023, 39 patients with confirmed relapsed/progressive high-risk neuroblastoma (median age 6 years, range 1-24) were treated with dB+TopoCyclo (n = 24) or dB+TOTEM/TEMIRI (n = 15) across 17 centers. In total, 163 chemo-immunotherapy cycles were administered, main toxicities were mild or moderate, with higher incidence of hematological adverse drug reactions with dB+TopoCyclo than dB+TOTEM/TEMIRI. Objective response rate was 42% for dB+TopoCyclo (CI95% 22-63%) and 40% for dB+TOTEM/TEMIRI (CI95% 16-68%). Similar objective response rates for dB+TopoCyclo and dB+TOTEM/TEMIRI in patients with relapsed/progressive high-risk neuroblastoma emphasize the importance of chemo-immunotherapy, irrespective of the chemotherapy backbone.

Sections du résumé

BACKGROUND BACKGROUND
Addition of anti-GD2 antibodies to temozolomide-based chemotherapy has demonstrated increased antitumor activity and progression-free survival in patients with relapsed/progressive high-risk neuroblastoma. However, chemo-immunotherapy is not yet approved for this indication. This study presents the chemo-immunotherapy experience in patients with relapsed/progressive high-risk neuroblastoma treated within the off-label use program of the Neuroblastoma Committee of the French Society of Pediatric Oncology (SFCE).
METHODS METHODS
Dinutuximab beta (dB) was administered alongside temozolomide-topotecan (TOTEM) or temozolomide-irinotecan (TEMIRI) at first disease relapse/progression or topotecan-cyclophosphamide (TopoCyclo) at further relapse/progression. Real-world data on demographics, treatment, antitumor activity and safety was collected from all patients after inclusion in SACHA-France (NCT04477681), a prospective national registry, which documents safety and efficacy data on innovative anticancer therapies prescribed to patients ≤ 25 years old as compassionate or off-label use.
RESULTS RESULTS
Between February 2021 and July 2023, 39 patients with confirmed relapsed/progressive high-risk neuroblastoma (median age 6 years, range 1-24) were treated with dB+TopoCyclo (n = 24) or dB+TOTEM/TEMIRI (n = 15) across 17 centers. In total, 163 chemo-immunotherapy cycles were administered, main toxicities were mild or moderate, with higher incidence of hematological adverse drug reactions with dB+TopoCyclo than dB+TOTEM/TEMIRI. Objective response rate was 42% for dB+TopoCyclo (CI95% 22-63%) and 40% for dB+TOTEM/TEMIRI (CI95% 16-68%).
CONCLUSION CONCLUSIONS
Similar objective response rates for dB+TopoCyclo and dB+TOTEM/TEMIRI in patients with relapsed/progressive high-risk neuroblastoma emphasize the importance of chemo-immunotherapy, irrespective of the chemotherapy backbone.

Identifiants

DOI: 10.1016/j.ejca.2024.114001 PMID: 38489858
pubmed: 38489858
pii: S0959-8049(24)00157-6
doi: 10.1016/j.ejca.2024.114001
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114001

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Pablo Berlanga reported an advisory role (institutional funding) for EUSA Pharma and grants and drugs for trials from Bayer outside the submitted work. No other disclosures were reported.

Auteurs

Patricia Raiser (P)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Gudrun Schleiermacher (G)

RTOP (Recherche Translationelle en Oncologie Pediatrique), U830 INSERM, Institut Curie, PSL Research University, 75005 Paris, France; SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), U830 INSERM, Institut Curie, PSL Research University, 75005 Paris, France.

Marion Gambart (M)

Department of Pediatric Oncology, Toulouse University Hospital, 31300 Toulouse, France.

Benoit Dumont (B)

Department of Pediatric Oncology, Institut d'Hématologie et d'Oncologie Pédiatrique/Centre Léon Bérard, 69008 Lyon, France.

Anne-Sophie Defachelles (AS)

Department of Pediatric Oncology, Oscar Lambret Cancer Center, 59000 Lille, France.

Estelle Thebaud (E)

Pediatric Immuno-Hemato-Oncology Unit, CHU Nantes, 44000 Nantes, France.

Julie Tandonnet (J)

Pediatric Hematology-Oncology Department, Centre Hospitalier Universitaire (CHU), 33000 Bordeaux, France.

Claudia Pasqualini (C)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Stéphanie Proust (S)

Department of Pediatric Oncology, University Hospital, 49100 Angers, France.

Natacha Entz-Werle (N)

Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, 67200 Strasbourg, France.

Isabelle Aerts (I)

RTOP (Recherche Translationelle en Oncologie Pediatrique), U830 INSERM, Institut Curie, PSL Research University, 75005 Paris, France; SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), U830 INSERM, Institut Curie, PSL Research University, 75005 Paris, France.

Lee A Ndounga-Diakou (LA)

Pharmacovigilance Unit, Clinical Research Direction, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Arnaud Petit (A)

Department of Pediatric Hematology and Oncology, Hôpital Armand Trousseau, 75012 Paris, France.

Chloe Puiseux (C)

Department of Pediatric Hemato-Oncology, University Hospital of Rennes, 35200 Rennes, France.

Camille Khanfar (C)

Department of Pediatric Oncology, CHU Amiens Picardie, 80054 Amiens, France.

Jeremie Rouger (J)

Department of Pediatric Hematology and Oncology, University Hospital of Caen, 14000 Caen, France.

Ludovic Mansuy (L)

Department of Pediatric Hematology-Oncology, Children's Hospital of Brabois, 54500 Vandoeuvre Les Nancy, France.

Joy Benadiba (J)

Department of Hemato-Oncology Pediatric, Nice University Hospital, 06000 Nice, France.

Frédéric Millot (F)

Department of Paediatric Haematology and Oncology, Centre Hospitalo-Universitaire de Poitiers, 86000 Poitiers, France.

Claire Pluchart (C)

Department of Paediatric Haematology and Oncology, Centre Hospitalo-Universitaire de Reims, 51100 Reims, France.

Salim Laghouati (S)

Pharmacovigilance Unit, Clinical Research Direction, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Birgit Geoerger (B)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France; INSERM U1015, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Gilles Vassal (G)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Dominique Valteau-Couanet (D)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France.

Pablo Berlanga (P)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, 94805 Villejuif, France. Electronic address: Pablo.Berlanga@gustaveroussy.fr.

Classifications MeSH