Is there a role for frontline combination therapy with a hypomethylating agent plus venetoclax for high risk MDS?  

Yes, if we extrapolate from AML and based on promising phase 1b clinical trial results (link below) so far, but venetoclax is not approved for MDS as of yet. Improved CR but also increased cytopenias, dose has not been confirmed yet. https://www.ashclinicalnews.org/on-location/ash-annual-meeting/ve...