Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

The ETCTN 10026 study tested decitabine and ipilimumab for transplant-naive advanced myelodysplastic syndrome/acute myeloid leukemia and relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Using single cell RNA sequencing, determinants of response (higher T/NK to myeloid cell ratio in responders) and resistance (insufficient clearance of AML clones) were identified and pharmacodynamics of decitabine (cytoreduction) and ipilimumab (increase in regulatory T cells) characterized. Single cell RNA sequencing of unselected bone marrow-derived mononuclear cells before treatment (screening), after 1 cycle of decitabine treatment alone (end of lead-in, EOLN), after combined treatment with decitabine and ipilimumab (C1, C2, ...), and at the end of treatment (EOT). NOTE FROM SUBMITTER: The raw data for this submission is being deposited in dbGAP under accession number phs003015.v1.