[Efficacy and safety analysis of BTK inhibitors combined with R-CHOP regimen in newly diagnosed double-expressor diffuse large B-cell lymphoma]

Objective: To evaluate the efficacy and safety of Bruton tyrosine kinase inhibitor (BTKi) combined with R-CHOP regimen in newly diagnosed double-expressor diffuse large B-cell lymphoma (DE-DLBCL) . Methods: A retrospective analysis was conducted on 95 patients with DLBCL meeting DE criteria by immunohistochemistry (MYC protein expression ≥ 40% , BCL-2 protein expression ≥ 50% ) treated at the First Affiliated Hospital of Nanjing Medical University between June 2021 and June 2024. Among them, 35 patients received BTKi (zanubrutinib, orelabrutinib, acalabrutinib) combined with R-CHOP (BTKi + R-CHOP group) , and 60 received R-CHOP regimen alone (R-CHOP group) . Outcomes included objective response rate (ORR) , complete response (CR) rate, progression-free survival (PFS) , overall survival (OS) , and safety. Results: The median age of the BTKi+R-CHOP group was 61 (range, 29-73) years. At the end of induction therapy, the BTKi+R-CHOP group had a higher ORR (94.3% vs 71.7% , P=0.008) and CR rate (91.4% vs 65.0% , P=0.006) than the R-CHOP group. After a median follow-up of 30 (range, 6-47) months, the 1- and 2-year PFS rates in the BTKi+R-CHOP group were 88.5% (95% CI: 78.5% -99.8% ) and 85.1% (95% CI: 73.8% -98.1% ) , respectively, and the 1- and 2-year OS rate was 94.3% (95% CI: 86.9% -100% ) . In the R-CHOP group, the 1-year and 2-year progression-free survival (PFS) rates were 61.7% (95% CI: 50.5% -75.3% ) and 48.8% (95% CI: 37.4% -63.6% ) , respectively; the 1-year and 2-year overall survival (OS) rates were 80.0% (95% CI: 70.5% -90.8% ) and 65.1% (95% CI: 53.7% -78.8% ) , respectively. Between-group differences were significant for both PFS (P=0.002) and OS (P=0.010) . Subgroup analyses showed high ORRs across clinical subgroups in the BTKi+R-CHOP group (all ORR>85% ) . Grade ≥ 3 adverse events primarily included neutropenia (28.6% ) and pulmonary infection (14.3% ) ; no fatal bleeding or cardiovascular events occurred. Conclusion: BTKi combined with R-CHOP significantly improved response rates and survival in patients with DE-DLBCL, with manageable safety.