Background:Background: Diffuse Large B-cell lymphoma (DLBCL) is common in the elderly patients, Some elderly patients can not tolerate the standard dose of R-CHOP due to age, poor physical condition, and severe complications. The overall response rate of elderly unfit DLBCL patients who received a reduced dose R-CHOP regimen was only 60%. It is extremely important to explore new therapeutic options. Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor which was still in an exploratory phase in patients with DLBCL.The efficacy of Zanubrutinib plus Rituximab in elderly unfit Patients with DLBCL is still unknown. Aims:Aims: This study was conducted to investigate the efficacy and safety of Zanubrutinib plus Rituximab in elderly unfit Patients With Previously Untreated Diffuse large-B cell Lymphoma in China. Methods:Methods: In the present study, a prospective, single-arm,single-center study was conducted (CHiCTR-2000039342).patients who fulfil the inclusion criteria were enrolled. Inclusion criteria: patients aged ≥65 years, pathologically confirmed DLBCL,and assessed unfit by Comprehensive Geriatric Assessment(IACA). Unfit patients defined as follows: i.e. IADL score ≤7, or age >75 years, or CCI score ≥3, or serum albumin <3.4 g/ml. Patients enrolled were planed to treat with Zanubrutinib combined with rituximab (Zanubrutinib 160 mg orally twice daily and rituximab 375 mg/m 2 day1 iv, every 28 days, ZR regimen), for a total of eight courses. After induction therapy, maintenance treatment with Zanubrutinib 160mg orally twice daily was given until disease progression or unacceptable toxicity. Efficacy was evaluated by PET/CT or enhanced Computed Tomography scan every two months, treatmentrelated adverse effects were evaluated in every one month. This study was approved by the Ethics Committee of

established that R-IPI very good category (Hazard Ratio [HR] = 2.51; 95% CI 1.14-5.51) and achieve complete response (HR = 6.89; 95% CI 3.4-13.95) were independent favorable risk factors for OS. In conclusion, this analysis of patients with DLBCL treated with R-CHOP in the real-world setting indicated that excellent outcomes are achieved, similar to those reported in the clinical trials.