Novel agents and pathways under investigation in MDS. Epigenetic modulators including HMA, HDACis, BET inhibitors, and LSD1i affect chromatin structure and transcription; immune checkpoint inhibition with a variety of monoclonal antibodies targeting the PD-1/PDL1 interaction, or CTLA-4 and its corresponding ligand facilitate antigen (MHC) recognition by T-cell receptors; IDH1/2 inhibition affects the mutant enzyme within mitochondria, splicing modulation acts preferentially on cells harboring mutations in splicing factors (splice mut); kinase inhibitors downregulate key signaling pathways including the RAS/MAPK and the PI3-K/AKT/m-TOR pathway.