Pirtobrutinib in the First Line and Next-Generation Strategies in CLL

Sameh Gaballa, MD, of Moffitt Cancer Center, asks where pirtobrutinib, the noncovalent Bruton tyrosine kinase (BTK) inhibitor newly approved for first-line chronic lymphocytic leukemia (CLL), fits and whether starting with it burns the bridge to covalent agents. Andrew H. Lipsky, MD, of Columbia University Irving Medical Center, is skeptical for most patients because resistance mutations arising on pirtobrutinib may not be salvaged by covalent BTK inhibitors. M. Yair Levy, MD, of Texas Oncology–Baylor Charles A. Sammons Cancer Center, agrees and notes it is unknown whether a noncovalent-first sequence matches covalent followed by noncovalent. The faculty then discuss sonrotoclax plus zanubrutinib, which produced near-100% response and undetectable measurable residual disease in more than 90% of treatment-naive patients, results Dr Lipsky calls antibody-level without an antibody, as well as BTK degraders such as tacabrutideg and the CaDAnCe-304 trial against pirtobrutinib.