Ibrutinib is an oral selective and irreversible inhibitor of Bruton’s tyrosine kinase (BTK), which inhibits signal transduction from the B-cell receptor, activation of B-cells, and interleukin-2-inducible T-cell kinases (ITK).37 Pre-clinical models found that mice who underwent HCT from BTK- or ITK-deficient donors did not develop chronic GVHD, suggesting a possible role for ibrutinib for the treatment of chronic GVHD.38 Ibrutinib became the first FDA-approved agent for chronic GVHD in 2017 based on the results of a single-arm Phase II trial (PYC-1129) (Table 3). Here, BTK is linked to chronic graft versus host disease.