A pilot study of genomic-guided induction therapy followed by immunotherapy with difluoromethylornithine maintenance for high-risk neuroblastoma.
DFMO
immunotherapy
maintenance
neuroblastoma
precision medicine
Journal
Cancer reports (Hoboken, N.J.)
ISSN: 2573-8348
Titre abrégé: Cancer Rep (Hoboken)
Pays: United States
ID NLM: 101747728
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
16
02
2022
received:
10
09
2021
accepted:
27
02
2022
pubmed:
1
4
2022
medline:
23
11
2022
entrez:
31
3
2022
Statut:
ppublish
Résumé
Survival for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapies. To study the feasibility and safety of incorporating a genomic-based targeted agent to induction therapy for HRNB as well as the feasibility and safety of adding difluoromethylornithine (DFMO) to anti-GD2 immunotherapy. Twenty newly diagnosed HRNB patients were treated on this multicenter pilot trial. Molecular tumor boards selected one of six targeted agents based on tumor-normal whole exome sequencing and tumor RNA-sequencing results. Treatment followed standard upfront HRNB chemotherapy with the addition of the selected targeted agent to cycles 3-6 of induction. Following consolidation, DFMO (750 mg/m Of the 20 subjects enrolled, 19 started targeted therapy during cycle 3 and 1 started during cycle 5. Eighty-five percent of subjects met feasibility criteria (receiving 75% of targeted agent doses). Addition of targeted agents did not result in toxicities requiring dose reduction of chemotherapy or permanent discontinuation of targeted agent. Following standard consolidation, 15 subjects continued onto immunotherapy with DFMO. This combination was well-tolerated and resulted in no unexpected adverse events related to DFMO. This study demonstrates the safety and feasibility of adding targeted agents to standard induction therapy and adding DFMO to immunotherapy for HRNB. This treatment regimen has been expanded to a Phase II trial to evaluate efficacy.
Sections du résumé
BACKGROUND
Survival for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapies.
AIMS
To study the feasibility and safety of incorporating a genomic-based targeted agent to induction therapy for HRNB as well as the feasibility and safety of adding difluoromethylornithine (DFMO) to anti-GD2 immunotherapy.
METHODS
Twenty newly diagnosed HRNB patients were treated on this multicenter pilot trial. Molecular tumor boards selected one of six targeted agents based on tumor-normal whole exome sequencing and tumor RNA-sequencing results. Treatment followed standard upfront HRNB chemotherapy with the addition of the selected targeted agent to cycles 3-6 of induction. Following consolidation, DFMO (750 mg/m
RESULTS
Of the 20 subjects enrolled, 19 started targeted therapy during cycle 3 and 1 started during cycle 5. Eighty-five percent of subjects met feasibility criteria (receiving 75% of targeted agent doses). Addition of targeted agents did not result in toxicities requiring dose reduction of chemotherapy or permanent discontinuation of targeted agent. Following standard consolidation, 15 subjects continued onto immunotherapy with DFMO. This combination was well-tolerated and resulted in no unexpected adverse events related to DFMO.
CONCLUSION
This study demonstrates the safety and feasibility of adding targeted agents to standard induction therapy and adding DFMO to immunotherapy for HRNB. This treatment regimen has been expanded to a Phase II trial to evaluate efficacy.
Identifiants
pubmed: 35355452
doi: 10.1002/cnr2.1616
pmc: PMC9675391
doi:
Substances chimiques
Eflornithine
ZQN1G5V6SR
Antineoplastic Agents
0
Immunologic Factors
0
RNA
63231-63-0
Types de publication
Multicenter Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1616Informations de copyright
© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.
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