Retrospective cohort study of causes of death among individuals with Lynch syndrome in the immunotherapy era

Individuals with Lynch syndrome (LS) predominantly develop mismatch repair-deficient/microsatellite-unstable (MMR-D/MSI-H) cancer, for which immunotherapy can yield long-term disease control. A retrospective cohort study at Dana-Farber Cancer Institute (Boston, MA) investigated causes of death among individuals with LS in the era of immunotherapy (since May 2017). In this study, 43% of cancer-related deaths among individuals with LS were due to MMR-proficient cancer, most commonly pancreatic and colorectal cancers. MMR-D/MSI-H cancers resistant to immunotherapy were also a frequent cause of death. The age at terminal cancer diagnosis differed by the affected LS gene. The authors conclude that with immunotherapy leading to excellent long-term outcomes among many LS-associated cancers, there is a need to better understand prevention/interception strategies against MMR-proficient/MS-stable cancer in LS.