Treatment Sequencing After Covalent BTK Inhibitors in CLL

Dr. Mazyar Shadman and Dr. Jennifer J. Huang discuss treatment selection for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) following covalent Bruton tyrosine kinase (BTK) inhibitor therapy. They compare pirtobrutinib with venetoclax-based regimens, highlighting differences in treatment duration, administration, and patient experience. Pirtobrutinib offers an oral, continuous treatment approach, whereas venetoclax-based therapy involves an initial dose ramp-up with frequent clinic visits but may provide a defined treatment period followed by time off therapy. The experts also review efficacy considerations, including progression-free survival findings from clinical studies, while acknowledging the limitations of comparing results across different study populations. They further explore retreatment with venetoclax-based therapy after a previous fixed-duration regimen. Dr. Huang notes that the interval between treatment completion and relapse can help inform this decision, with approximately 2 years discussed as a potential consideration. Dr. Shadman emphasizes individualizing treatment choices according to prior response, comorbidities, and patient-specific factors.