MLH1 germline loss-of-function in endometrial produces dMMR/MSI-H phenotype. Pan-tumor MS...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-MLH1-GERMLINE-ENDOMETRIAL |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-ENDOMETRIAL |
| Sources | SRC-CIVIC SRC-ESGO-ENDOMETRIAL-2025 SRC-NCCN-UTERINE-2025 |
Actionability Facts
| Biomarker | BIO-DMMR-IHC |
|---|---|
| Variant | MLH1 germline loss-of-function (dMMR / MSI-H) |
| Disease | DIS-ENDOMETRIAL |
| ESCAT tier | IA |
| Recommended combinations | dostarlimab + carbo/paclitaxel (1L advanced dMMR, RUBY), pembrolizumab + carbo/paclitaxel (1L advanced, NRG-GY018), dostarlimab monotherapy (2L+ dMMR, GARNET), pembrolizumab monotherapy (pan-tumor MSI-H) |
| Evidence summary | MLH1 germline loss-of-function in endometrial produces dMMR/MSI-H phenotype. Pan-tumor MSI-H ICI eligibility (pembrolizumab per KEYNOTE-158, dostarlimab per GARNET) supersedes tumor-specific lines via tissue-agnostic FDA approval. Advanced/recurrent dMMR endometrial: dostarlimab + carbo/paclitaxel 1L (RUBY) and pembrolizumab + carbo/paclitaxel (NRG-GY018) doubled PFS. Dostarlimab/pembrolizumab monotherapy in 2L+. Adjuvant ICI in early-stage dMMR under study. |
Notes
Germline MLH1 loss → cascade testing mandatory (Lynch syndrome). Family meets Amsterdam/Bethesda criteria. Pan-tumor MSI-H ICI eligibility supersedes tumor- specific lines.
Used By
No reverse references found in the YAML corpus.