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Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab.
- Source :
-
Immunogenetics . May2019, Vol. 71 Issue 5/6, p433-436. 4p. - Publication Year :
- 2019
-
Abstract
- There 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-function MBD4 mutation. Here, we report on another UM patient who carried an MBD4 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 in MBD4 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 of MBD4 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 of MBD4 in the screening of potential UM-prone families as well as stratification of immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NONSENSE mutation
*UVEAL diseases
*IPILIMUMAB
*MELANOMA
*THERAPEUTICS
*BRAF genes
Subjects
Details
- Language :
- English
- ISSN :
- 00937711
- Volume :
- 71
- Issue :
- 5/6
- Database :
- Academic Search Index
- Journal :
- Immunogenetics
- Publication Type :
- Academic Journal
- Accession number :
- 136505057
- Full Text :
- https://doi.org/10.1007/s00251-019-01108-x