Efficacy and safety analysis of a novel BTK inhibitor in patients with mantle cell lymphoma harboring TP53 mutations

OBJECTIVE: To rigorously evaluate the efficacy and safety of a novel Bruton tyrosine kinase inhibitor (BTKi), alone or in combination with venetoclax, in patients with TP53-mutated mantle cell lymphoma (MCL), focusing on survival outcomes, depth of response, minimal residual disease (MRD), clearance, and treatment-emergent toxicities. METHODS: We conducted a retrospective, observational cohort study of consecutive adults with TP53-mutated MCL treated with BTKi-based regimens between January 2022 and December 2025. Patients were assigned to BTKi monotherapy (ibrutinib or acalabrutinib; n = 108) or BTKi plus venetoclax (n = 112). Clinical, pathological, and genomic data were recorded using standardized electronic case-report forms. Responses were assessed according to contemporary MCL criteria, and recurrence/progression-free survival (RFS/PFS) and overall survival (OS) were calculated from predefined time points. RESULTS: Combined treatment significantly prolonged median RFS from 11 to 34 months (HR for recurrence or death 0.42, 95% CI 0.29-0.61; P