Dr Matthew Davids speaks to ecancer about results from the phase 3 BRUIN CLL 322 trial evaluating fixed-duration pirtobrutinib, a noncovalent BTK inhibitor, in combination with venetoclax rituximab in patients with previously treated chronic lymphocytic leukaemia and small lymphocytic lymphoma.

The study compares this triplet regimen against standard venetoclax rituximab therapy in a randomized global trial population, including a high proportion of patients previously exposed to covalent BTK inhibitors.

At a median follow-up of 27.3 months, the addition of pirtobrutinib significantly improved investigator-assessed progression free survival, with a 24-month PFS of 86.9 percent compared with 71.8 percent for standard therapy.

Dr Davids says that the benefit was consistent across high-risk subgroups, including patients with del 17p TP53 mutations and those with prior BTK inhibitor exposure. The triplet regimen also achieved higher rates of undetectable minimal residual disease at the end of treatment and improved time to next treatment, while overall survival data remain immature.

These results support fixed-duration pirtobrutinib venetoclax rituximab as a potential new standard of care in relapsed or refractory CLL, including in patients previously treated with covalent BTK inhibitors.