ARQ 531 is a potent, reversible inhibitor of both wild type and ibrutinib-resistant C481S-mutant BTK. This new agent suppresses oncogenic BCR signaling in chronic lymphocytic leukemia (CLL) cells resistant to ibrutinib and has demonstrated antitumor activity superior to ibrutinib in CLL. Jennifer Woyach, MD, The Ohio State University, Columbus, OH, outlines the study (NCT03162536) assessing the safety and tolerability of ARQ 531. Data indicate that ARQ 531 has a manageable safety profile and shows antitumor activity in CLL patients resistant to covalent BTK inhibitors, and promising pre-clinical activity in Richter’s transformation. This interview took place at the American Society of Hematology (ASH) 2019 Annual Meeting and Exposition in Orlando, FL.