Sequencing BTK inhibitor therapy in CLL: treatment considerations and emerging strategies

This podcast explores sequencing strategies and treatment considerations for BTK inhibitors in chronic lymphocytic leukemia (CLL). Jennifer Brown, MD, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses treatment options following covalent BTK inhibitor therapy, including venetoclax-based regimens and non-covalent BTK inhibitors. Gianluca Gaidano, MD, PhD, University of Eastern Piedmont, Vercelli, Italy, examines treatment selection after BTK inhibitor therapy, the improved safety profile of second-generation BTK inhibitors, and the Phase III AMPLIFY trial (NCT03836261) evaluating fixed-duration acalabrutinib plus venetoclax. Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany, reviews the CLL-FRAIL study investigating continuous acalabrutinib in older and frail patients with CLL. Kerry Rogers, MD, The Ohio State University, Columbus, OH, discusses strategies to overcome BTK inhibitor resistance, including fixed-duration combinations and long-term follow-up from a Phase II study of venetoclax plus ibrutinib in patients with BTK inhibitor resistance mutations. Finally, Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, presents findings from the Phase III BRUIN CLL-322 trial (NCT06073821) evaluating fixed-duration pirtobrutinib, venetoclax, and rituximab in previously treated CLL.