Long-Term BTK Inhibitor Safety and Options After Progression on a Covalent BTK Inhibitor

Sameh Gaballa, MD, of Moffitt Cancer Center, asks what to watch for in patients who have been on a Bruton tyrosine kinase (BTK) inhibitor for years. Andrew H. Lipsky, MD, of Columbia University Irving Medical Center, says adverse events level off after the first 6 months, with SEQUOIA showing even neutropenia declining by years 5 and 6. M. Yair Levy, MD, of Texas Oncology–Baylor Charles A. Sammons Cancer Center, first assesses adherence as a marker of tolerability. After progression on a covalent BTK inhibitor, Dr Lipsky sends resistance panels but says they rarely change his plan; because second-line pirtobrutinib progression-free survival in BRUIN fell short of his hopes, he often prefers a venetoclax-based regimen when a patient needs a long next line, reserving the noncovalent agent for later and keeping BTK degraders in mind. Dr Levy highlights emerging combinations of pirtobrutinib with venetoclax and says patient preference drives every choice.