Barbara Eichhorst, MD, University of Cologne, Cologne, Germany, discusses the design and results from two prospective phase II trials evaluating tirabrutinib in combination with idelalisib or entospletinib as dual therapy, and as triple therapy adding obinutuzumab [CLLRUmbrella1 (NCT02968563) and CLLRUmbrella2 (NCT02983617)]. Results from the two studies are comparable; combination therapy with tirabrutinib, idelalisib and obinutuzumab had good efficacy but relevant toxicity, while the tirabrutinib, entospletinib and obinutuzumab regimen was tolerable and demonstrated excellent therapeutic activity in relapsed or refractory chronic lymphocytic leukemia (CLL) patients. This interview took place at the American Society of Hematology (ASH) 2019 Annual Meeting and Exposition in Orlando, FL.