The FDA has approved pirtobrutinib (Jaypirca) for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who do not have del(17p), using data from the phase 3 BRUIN CLL-313 trial. The decision positions the noncovalent BTK inhibitor as a first-line option alongside, rather than after, chemoimmunotherapy choices. In BRUIN CLL-313, pirtobrutinib significantly delayed disease progression compared with bendamustine plus rituximab, with median progression-free survival not estimable versus 33.5 months in the control arm (HR 0.20). Overall survival remains immature, with fewer deaths recorded in the pirtobrutinib group. Because patients can cross over after progression, the interim survival picture is still developing. The approval nonetheless changes upfront treatment discussions by giving clinicians a targeted pathway for an important biomarker-defined subgroup.