Abstract
Salvage chemotherapy followed by autologous stem cell transplantation (auto-SCT) is effective for relapsed or refractory DLBCL (R/R DLBCL), but many patients are ineligible due to age, comorbidities, tolerance, economy and other factors. Zanubrutinib, a selective Bruton's tyrosine kinase inhibitor, has modest antitumor activity in R/R DLBCL. This study aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in transplant-ineligible patients with R/R non-GCB DLBCL. We retrospectively reviewed patients with R/R non-GCB DLBCL treated with zanubrutinib combined with BR (bendamustine + rituximab; ZBR) or R2 (lenalidomide + rituximab; ZR2) between January 2019 and July 2023. A total of 49 patients were enrolled with a median age of 60 years. The best objective response rate (ORR) was 57.1% with a complete response (CR) rate of 12.2% in the entire cohort. 19 patients were treated with ZBR and 30 patients were treated with ZR2. The ORR of ZBR and ZR2 cohort was 63.2% and 53.3% respectively. With a median follow-up duration of 22 months, the median progression free survival (PFS) was 6.0 months, and overall survival (OS) was 21.0 months. Patients in CD79B ± MYD88 mutated subgroup had a significantly higher ORR (86.7% v 44.1%, P = 0.006) and longer PFS (8.1 v 4.9 months, P = 0.009) compared to those in CD79B ± MYD88 non-mutated subgroup. A significant PFS and OS benefit was observed in the patients who responded to the treatment. The most common grade 3/4 adverse events were neutropenia (46. 9%) and thrombocytopenia (44.9%). Zanubrutinib combined with BR or R2 showed promising efficacy and manageable toxicity, which may be a potential treatment option for patients with transplant-ineligible R/R non-GCB DLBCL.