Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
19
01
2023
accepted:
15
08
2023
pmc-release:
16
10
2024
medline:
1
11
2023
pubmed:
17
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38). Twenty-four of 61 (39%) ICB-treated patients who subsequently underwent surveillance colonoscopy had premalignant polyps. Within matched pre-ICB and post-ICB follow-up periods, the overall rate of tumor development was unchanged; however, on subgroup analysis, a decreased incidence of post-ICB visceral tumors was observed. These data suggest that ICB treatment of LS-associated tumors does not eliminate risk of new neoplasia development, and LS-specific surveillance strategies should continue. These data have implications for immunopreventative strategies and provide insight into the immunobiology of dMMR tumors.
Identifiants
pubmed: 37845474
doi: 10.1038/s41591-023-02544-9
pii: 10.1038/s41591-023-02544-9
pmc: PMC10870255
mid: NIHMS1961754
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2458-2463Subventions
Organisme : NCI NIH HHS
ID : R21 CA252519
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA092629
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA279922
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221745
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000457
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA184746
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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