Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease. 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. Overall design: 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.