Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab
AbstractThere is currently no effective treatment for metastasised uveal melanoma (UM). Recently, it was reported that a UM patient was responsive to checkpoint inhibitor (CI) treatment, due to a high tumour mutation burden correlated with a germline loss-of-functionMBD4 mutation. Here, we report on another UM patient who carried anMBD4 germline nonsense variant (p.Leu563Ter) and her tumour showed a fivefold higher than average mutation burden. We confirmed the association between germline loss-of-function variant inMBD4 and CI response. The patient experienced stable disease (10 months) and survived 2 years with metastatic disease, which is twice as long as median survival. Additionally, the frequency ofMBD4 loss-of-function variants in reported UM cohorts was> 20 times higher than in an aggregated population genome database (P < 5 × 10−5), implying a potential role as UM predisposition gene. These findings provide a strong basis for the inclusion ofMBD4 in the screening of potential UM-prone families as well as stratification of immunotherapy.
Source: Immunogenetics - Category: Genetics & Stem Cells Source Type: research
More News: Databases & Libraries | Eye Cancers | Genetics | Immunotherapy | Melanoma | Skin Cancer | Uveal Melanoma | Yervoy