Phase III BRUIN CLL-322 trial: PVR vs VR for R/R CLL

Results from the randomized phase III BRUIN CLL-322 (NCT04965493) trial evaluating fixed-duration pirtobrutinib + venetoclax + rituximab (PVR; n = 321) vs venetoclax + rituximab (VR; n = 318) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) were presented by Matthew Davids at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), investigator-assessed PFS, time to next treatment (TTNT), overall response rate (ORR), and safety. 

Key data: At a median follow-up of 27.3 months, the median IRC-assessed PFS was not estimable (NE; 95% confidence interval [CI], 43.3–NE) with PVR vs 39.7 months (95% CI, 35.9–NE) with VR (hazard ratio [HR], 0.547; 95% CI, 0.400–0.748; p = 0.0001). The 24-month PFS rates were 86.9% (95% CI, 82.3–90.4) vs 71.8% (95% CI, 65.7–77.0). The PFS benefit was consistent across prespecified subgroups, including patients who had received post-covalent Bruton’s tyrosine kinase inhibitor (cBTKi), those receiving second-line treatment, and those with high-risk disease. The 24-month TTNT rates were 87.7% vs 77.2% (p < 0.0001). With a median follow-up of 30.6 months, OS interim data were immature; 24-month OS rates were 90.6% vs 89.2% (p = 0.6157). The ORRs were 88.5% vs 83.3% (p = 0.0618), with complete responses (CRs) in 31.8% vs 23.3% of patients. The most common Grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia/neutrophil count decrease (49.7% vs 43.7%), anemia (6.3% vs 10.6%), and COVID-19 (5.4% vs 3.9%). Pirtobrutinib’s favorable cardiovascular profile was preserved, with low rates of any grade atrial fibrillation/flutter (3.5%), hemorrhage (14.2%), and hypertension (12.0%). 

Key learning: PVR demonstrated superior PFS and TTNT compared with VR, with a manageable safety profile and no new safety signals, establishing PVR as a potential standard of care (SoC) option for patients with R/R CLL/SLL.