An N-of-1 Trial of Itacitinib for a Patient with Aplastic Anemia Associated with a Gain-of-Function Variant in STAT1

Abstract An 18-year-old man presented with aplastic anemia, and exome sequencing identified a germline gain-of-function variant in the gene STAT1. Treatment with itacitinib, an investigational selective Janus Kinase 1 (JAK1) inhibitor, resulted in prompt recovery of hematopoiesis. An exhausted CD8+ T cell population and myeloid populations enriched for an interferon- y signature correlated with disease activity. Patient bone marrow sections displayed increased phospho-STAT1 staining, as did other idiopathic aplastic anemia cases, suggesting a shared pathophysiologic mechanism. This study describes the success and mechanism of a molecularly targeted therapy with potential implications for the treatment of aplastic anemias and other autoimmune disorders.