Overview
- Pirtobrutinib significantly improved progression-free survival over bendamustine plus rituximab in untreated CLL/SLL in BRUIN CLL-313, cutting the risk of progression or death by about 80% (HR 0.199).
- At roughly 24 to 28 months of follow-up in CLL-313, PFS was 93.4% with pirtobrutinib versus 70.7% with BR, with fewer grade 3 or higher adverse events and fewer treatment discontinuations on pirtobrutinib.
- In the head-to-head BRUIN CLL-314 trial (n=662), pirtobrutinib achieved a higher overall response rate than ibrutinib in BTK inhibitor–naive CLL/SLL (87.0% vs 78.5% ITT) with early PFS trends favoring pirtobrutinib, most notably in treatment‑naive patients (HR 0.239).
- Safety findings favored pirtobrutinib over ibrutinib in CLL-314, with lower rates of atrial fibrillation/flutter (2.4% vs 13.5%), hypertension (10.6% vs 15.1%), and fewer dose reductions (7.9% vs 18.2%).
- Final phase 1/2 BRUIN data showed an 81.6% ORR and durable benefit after prior covalent BTK inhibitors, and the FDA converted pirtobrutinib’s CLL/SLL indication to full approval on December 3, 2025.