Synergy between TMZ and individualized multimodal immunotherapy to improve overall survival of IDH1 wild-type MGMT promoter-unmethylated GBM patients.
Adult
Humans
Temozolomide
/ therapeutic use
Dacarbazine
/ therapeutic use
DNA Modification Methylases
/ genetics
Glioblastoma
/ therapy
Antineoplastic Agents, Alkylating
/ therapeutic use
DNA Repair Enzymes
/ genetics
Retrospective Studies
Brain Neoplasms
/ genetics
Tumor Suppressor Proteins
/ genetics
DNA Methylation
Immunotherapy
Isocitrate Dehydrogenase
/ genetics
Journal
Genes and immunity
ISSN: 1476-5470
Titre abrégé: Genes Immun
Pays: England
ID NLM: 100953417
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
02
09
2021
accepted:
12
01
2022
revised:
20
12
2021
pubmed:
18
2
2022
medline:
21
12
2022
entrez:
17
2
2022
Statut:
ppublish
Résumé
The prognosis of IDH1 wild-type MGMT promoter-unmethylated GBM patients remains poor. Addition of Temozolomide (TMZ) to first-line local treatment shifted the median overall survival (OS) from 11.8 to 12.6 months. We retrospectively analyzed the value of individualized multimodal immunotherapy (IMI) to improve OS in these patients. All adults meeting the criteria and treated 06/2015-06/2021 were selected. Thirty-two patients (12f, 20m) had a median age of 47 y (range 18-69) and a KPI of 70 (50-100). Extent of resection was complete (11), <complete (12) or not documented (9). Seven patients were treated with surgery/radio(chemo)therapy and subsequent IMI (Group-1); 25 patients were treated with radiochemotherapy followed by maintenance TMZ plus IMI during and after TMZ (Group-2). Age, KPI and extent of resection were not different amongst both groups. The median OS of group-1 patients was 11 m (2 y OS: 0%). Surprisingly the median OS of group-2 patients was 22 m with 2 y OS of 36% (CI95%: 16-57), which was significantly (Log-rank: p = 0.0001) different from group-1. The data suggest that addition of IMI after local therapy on its own has no relevant effect on OS in these GBM patients, similar to maintenance TMZ. However, the combination of both TMZ + IMI significantly improved OS.
Identifiants
pubmed: 35173295
doi: 10.1038/s41435-022-00162-y
pii: 10.1038/s41435-022-00162-y
pmc: PMC9758045
doi:
Substances chimiques
Temozolomide
YF1K15M17Y
Dacarbazine
7GR28W0FJI
DNA Modification Methylases
EC 2.1.1.-
Antineoplastic Agents, Alkylating
0
DNA Repair Enzymes
EC 6.5.1.-
Tumor Suppressor Proteins
0
MGMT protein, human
EC 2.1.1.63
IDH1 protein, human
EC 1.1.1.42.
Isocitrate Dehydrogenase
EC 1.1.1.41
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
255-259Informations de copyright
© 2022. The Author(s).
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