A comprehensive analysis of pirtobrutinib in Chinese patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): Results from the phase 3 study BRUIN CLL-321.

BRUIN CLL-321 is the first prospective, randomized study conducted in covalent BTK inhibitor (cBTKi) pretreated chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients. In this heavily pretreated population, pirtobrutinib significantly improved progression-free survival (PFS) compared to investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BendaR). This report presents results from Chinese patients enrolled in BRUIN CLL-321, who were randomized 1:1 to pirtobrutinib (200 mg once daily) or IC of BendaR (idelalisib is not approved in China). End-points included independent review committee (IRC)-assessed PFS, investigator (INV)-assessed PFS, overall survival (OS), event-free survival (EFS), time to next treatment (TTNT) and safety. Among 40 Chinese patients (pirtobrutinib n = 19; BendaR n = 21), IRC-assessed PFS favoured pirtobrutinib (stratified hazard ratio [HR] = 0.281; 95% confidence interval [CI], 0.070-1.125, nominal p = 0.0554), with median PFS not reached versus 10.6 months with BendaR; INV-assessed PFS supported these findings. TTNT (HR = 0.150; 95% CI, 0.031-0.728) and EFS (HR = 0.322; 95% CI, 0.094-1.101) were also improved. A trend towards OS benefit was observed (HR = 0.343; 95% CI, 0.031-3.787). Pirtobrutinib showed a favourable safety profile, with fewer grade ≥3 treatment-emergent adverse events (36.8% vs. 93.3%) and serious adverse events (15.8% vs. 46.7%). These findings support pirtobrutinib as a clinically active and tolerable option for cBTKi-pretreated Chinese CLL/SLL population.