Journal Article

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

Foote, Michael B., Bandlamudi, Chaitanya, Shia, Jinru, Latham, Alicia, Borio, Matilde, Cercek, Andrea, Markowitz, Arnold J., Harrold, Emily C., Offit, Kenneth, Rathkopf, Dana, Rousseau, Benoit, Patel, Zalak, Richards, Allison L., Janjigian, Yelena Y., O’Reilly, Eileen M., Solit, David B., Vanderbilt, Chad, Diaz, Luis A., Segal, Neil H., Murciano-Goroff, Yonina R., Weiser, Martin R., Maio, Anna, Keane, Fergus, Rosenberg, Jonathan E., Kemel, Yelena, Saltz, Leonard, Rossi, Anthony M., Desai, Avni, Mandelker, Diana, Carlo, Maria I., Yaeger, Rona, Reidy, Diane, Liu, Ying L., Stadler, Zsofia K., Ilson, David, Walch, Henry, Walsh, Michael F., Berger, Michael F.

2023

Overview

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. In a retrospective analysis of patients with Lynch syndrome and primary cancers treated with immune checkpoint inhibitors, 12% developed subsequent malignancies, suggesting that this treatment may not eliminate risk in individuals predisposed to mismatch repair-deficient cancers, and ongoing surveillance is warranted.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/67/68 / 692/699/67/1059/2325 / 692/699/67/2195 / Biomedical and Life Sciences / Biomedicine / Brain Neoplasms / Brief Communication / Cancer / Cancer Research / Colon / Colorectal cancer / Colorectal Neoplasms - pathology / Colorectal Neoplasms, Hereditary Nonpolyposis - complications / Colorectal Neoplasms, Hereditary Nonpolyposis - drug therapy / Colorectal Neoplasms, Hereditary Nonpolyposis - genetics / Genetic disorders / Humans / Immune Checkpoint Inhibitors / Infectious Diseases / Malignancy / Metabolic Diseases / Metastases / Mismatch repair / Molecular Medicine / Neoplastic Syndromes, Hereditary / Neurosciences / Polyps / Risk / Subgroups / Surveillance / Tumors