New Protocol: Pirtobrutinib with Venetoclax and Rituximab for CLL

In patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma, the addition of pirtobrutinib to venetoclax and rituximab significantly improved progression-free survival, with a 45% reduction in the risk of progression or death. The median progression-free survival in the pirtobrutinib group was not reached compared to 39.7 months in the venetoclax-rituximab group. The safety profile was manageable and consistent with the known profiles of the individual drugs.

Study

Open-label, multicentre, randomised, controlled, phase 3 trial [BRUIN CLL-322, NCT04965493]

Previously treated chronic lymphocytic leukemia

Pirtobrutinib + Venetoclax + Rituximab (28 cycles, n=321) vs Venetoclax + Rituximab (25 cycles, n=318)

Efficacy

IRC-assessed ORR: 88.5% vs 83.3% (PVR vs. VR)

mPFS: Not reached vs 39.7 mos (HR 0.547 [0.400-0.748])

24-mo PFS: 87% vs 72%

mOS: Not reached vs Not reached (HR 0.891 [0.568-1.398])

Safety

Grade >=3 AE: neutropenia (27% vs 25%), anemia (6% vs 11%), pneumonia (11% vs 7%), thrombocytopenia (5% vs 5%), infection (34% vs 23%), haemorrhage (3% vs 3%), atrial fibrillation and atrial flutter (2% vs 1%)

Treatment discontinuations due to drug-related AE: 5% vs 5%