Paolo Ghia, MD, Università Vita-Salute San Raffaele, Milan, Italy, discusses evolving strategies using Bruton’s tyrosine kinase (BTK) inhibitors to treat chronic lymphocytic leukemia (CLL), commenting on the development of second-generation and third-generation BTK inhibitors which aim to achieve an improved safety and tolerability profile, in particular in regards to cardiovascular toxicities. Dr Ghia also talks on the development of pirtobrutinib, a third-generation non-covalent BTK inhibitor, highlighting the benefits of it being reversible and describing how this impacts drug sequencing. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.