Dr. Lee on the Association of MSI-H, dMMR, and TMB-H Features in Endometrial Cancer

Sarah Lee, MD, MBA, First-Year Fellow, NYU Langone Health, discusses the association of microsatellite instability–high (MSI-H), mismatch repair deficiency (dMMR), and tumor mutational burden–high (TMB-H) features in endometrial cancer. 

Several FDA indications have been granted for patients with endometrial cancer, Lee says. These include pembrolizumab (Keytruda), which was FDA in 2017 for patients with unresectable or metastatic, MSI-H or dMMR solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. Pembrolizumab was also approved in 2020 for the treatment of patients with unresectable or metastatic TMB-H solid tumors that have progressed following prior treatment and who have no satisfactory alterative treatment options, Lee explains. Moreover, findings from the ongoing phase 1 GARNET trial (NCT02715284) led to the 2021 FDA accelerated approval of the checkpoint inhibitor dostarlimab-gxly (Jemperli) for patients with dMMR recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen, Lee adds.

The regulatory decisions brought up the question of: What is the overlap between these 3 disease features? It is important to consider broad molecular testing for MSI-H, dMMR, and TMB-H features to determine which patients that can qualify for immunotherapy, Lee concludes.