The FDA approved pirtobrutinib (Jaypirca) for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma without del(17p), based on the Phase 3 BRUIN CLL-313 trial. The decision expands the noncovalent BTK inhibitor’s use beyond relapsed settings and reinforces targeted therapy as first-line standard for appropriate CLL patients. In BRUIN CLL-313, pirtobrutinib significantly delayed disease progression versus bendamustine plus rituximab, with median progression-free survival not estimable versus 33.5 months in the comparator arm (HR 0.20). Overall survival was immature, with deaths still limited in both groups. The approval shifts treatment planning for older or comorbidity-heavy patients who may receive limited lines of therapy, increasing pressure on rivals to demonstrate competitive efficacy and durable safety in initial CLL regimens.