Synapse - Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade

Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade Journal Article

Authors:	Harrold, E. C.; Foote, M. B.; Rousseau, B.; Walch, H.; Kemel, Y.; Richards, A. L.; Keane, F.; Cercek, A.; Yaeger, R.; Rathkopf, D.; Segal, N. H.; Patel, Z.; Maio, A.; Borio, M.; O’Reilly, E. M.; Reidy, D.; Desai, A.; Janjigian, Y. Y.; Murciano-Goroff, Y. R.; Carlo, M. I.; Latham, A.; Liu, Y. L.; Walsh, M. F.; Ilson, D.; Rosenberg, J. E.; Markowitz, A. J.; Weiser, M. R.; Rossi, A. M.; Vanderbilt, C.; Mandelker, D.; Bandlamudi, C.; Offit, K.; Berger, M. F.; Solit, D. B.; Saltz, L.; Shia, J.; Diaz, L. A. Jr; Stadler, Z. K.
Article Title:	Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade
Abstract:	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. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title:	Nature Medicine
Volume:	29
Issue:	10
ISSN:	1078-8956
Publisher:	Nature Publishing Group
Date Published:	2023-10-01
Start Page:	2458
End Page:	2463
Language:	English
DOI:	10.1038/s41591-023-02544-9
PUBMED:	37845474
PROVIDER:	scopus
PMCID:	PMC10870255
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85174268360&doi=10.1038%2fs41591-023-02544-9&partnerID=40&md5=bd5399f8fe7d76f2be3d56b1aafcaf84
Notes:	Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Zsofia Stadler -- Source: Scopus