BRUIN CLL-313: Pirtobrutinib vs BR for treatment-naïve CLL/SLL

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Wojciech Jurczak presented first results from the phase III BRUIN CLL-313 trial (NCT05023980) investigating the efficacy and safety of pirtobrutinib, a Bruton tyrosine kinase inhibitor (BTKi), vs bendamustine + rituximab (BR) in 282 treatment-naïve patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The primary endpoint was progression-free survival (PFS), and the key secondary endpoint was overall survival (OS).

Key data: At a median follow-up of 28.1 months, pirtobrutinib demonstrated a statistically significant and clinically meaningful PFS improvement, with an 80% reduction in the risk of progressive disease (PD) or death compared with BR (hazard ratio [HR], 0.20; 95% confidence interval [CI], 0.11–0.37; p < 0.0001). The 24-month PFS rate was 93.4% (95% CI, 87.6–96.5) for pirtobrutinib vs 70.7% (95% CI, 61.5–78.1) for BR. The 24-month OS rate trended in favor of pirtobrutinib vs BR (97.8% vs 93.0%). The incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) was 40.0% with pirtobrutinib and 67.4% with BR, with discontinuation due to TEAEs occurring in 4.3% and 15.4% of patients, respectively. The incidence of any grade of atrial fibrillation and flutter in patients aged ≥75 years remained low (5.0% vs 4.3%).

Key learning: Pirtobrutinib demonstrated one of the largest treatment effects observed for a single-agent BTKi compared with BR, with a favorable safety profile. The data suggest that pirtobrutinib shows potential as a new standard of care treatment for treatment-naïve patients with CLL/SLL, particularly older patients.