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‹ Fri · 10 Jul 2026
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Fixed-duration pirtobrutinib plus venetoclax-rituximab versus venetoclax-rituximab for patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (BRUIN CLL-322): an open-label, multicentre, randomised, controlled, phase 3 trial.

Adding pirtobrutinib to standard therapy cut progression risk nearly in half for patients whose previous leukemia treatments had stopped working.

The BRUIN CLL-322 Phase 3 trial randomised 639 patients with previously treated CLL to receive pirtobrutinib (non-covalent BTK inhibitor) added to the venetoclax-rituximab standard regimen or VR alone. Adding pirtobrutinib cut the risk of progression or death by 45% (HR 0.547, p=0.0001), with 87% vs 72% of patients progression-free at 24 months, including those who had already failed a covalent BTK inhibitor.

What the study was

Study design
phase_3_rct
Category
hematologic_malignancies
Maturity
Potentially Practice-Changing
Journal
Lancet

Why it surfaced

Lancet Phase 3 RCT in R/R CLL—highest evidence grade, addresses the unmet need of fixed-duration therapy post-covalent BTKi failure, practice-changing potential; Eli Lilly-sponsored but masked IRC review and consistent subgroup benefit reduce bias concern.

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