Acalabrutinib is an irreversible inhibitor of Bruton's tyrosine kinase with greater specificity for the enzyme than the first-in-class agent, ibrutinib. It had substantial antitumor effects in a phase 1–2 study involving patients with relapsed chronic lymphocytic leukemia. Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia among adults. Although chemoimmunotherapy prolongs the duration of remission and overall survival among most patients with CLL, 1 , 2 relapse virtually always occurs. This has prompted aggressive discovery efforts for new therapies in CLL. Because B-cell receptor signaling is a driving factor for CLL tumor-cell survival, 3 , 4 proximal kinases involved in this pathway have been therapeutic targets. Bruton’s tyrosine kinase (BTK) is immediately downstream of the B-cell receptor and is essential for the activation of several tumor-cell survival pathways relevant to CLL. 5 In addition, BTK is involved in chemokine-mediated homing and adhesion . . .