The FDA approved pirtobrutinib (Jaypirca) for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who do not have del(17p), marking a shift to first-line use for the noncovalent BTK inhibitor. The decision is based on the phase 3 BRUIN CLL-313 trial, which compared pirtobrutinib with bendamustine plus rituximab (BR) in 282 patients. In BRUIN CLL-313, median progression-free survival was not estimable in the pirtobrutinib arm versus 33.5 months with BR (hazard ratio 0.20; P<.0001). Overall survival data were immature. Investigators reported a safety and tolerability profile consistent with previously established pirtobrutinib experience. The label expansion matters for treatment sequencing in CLL, where many patients may receive only one or two lines of therapy due to age and comorbidities. With this approval, clinicians can consider pirtobrutinib earlier rather than waiting for relapsed or refractory disease.