Implementing a functional precision medicine tumor board for acute myeloid leukemia.

We generated ex vivo drug response and multi-omics profiling data for a prospective series of 252 samples from 186 acute myeloid leukemia (AML) patients. Functional precision medicine tumor board (FPMTB) integrated clinical, molecular and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of AML patients and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five AML patients to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled identification of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3-inhibitors. Integration of molecular profiling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommendations, providing a paradigm for individualized implementation of functional precision cancer medicine.