This trial is a prospective, single-center, randomized controlled clinical research. The intention is to evaluate the efficacy and safety of zanubrutinib combined with BEAM as a pretreatment regimen for ASCT in relapsed and refractory DLBCL patients through prospective clinical studies.

This trial includes 66 patients with recurrent or refractory DLBCL, who will be randomly divided into a 1:1 combination of zanubrutinib and BEAM regimen pretreatment (experimental group) or a standard BEAM regimen pretreatment (control group), and then undergo ASCT treatment. The entire trial includes a screening period (before the start of autologous stem cell transplantation pretreatment), a treatment period (-8 days to -2 days, a total of 7 days), and a follow-up period (2 years after autologous stem cell transplantation)

Inclusion Criteria:

1. According to world Health Organization (WHO) classification of disease, diffuse large B-cell lymphoma was confirmed by histology, CR or PR after second-line and above treatment;

2. 18≤ age ≤65 years old, male or female;

3. ECOG score 0-2;

4. No serious organic lesions in the main organs, meeting the requirements of the following laboratory examination indicators (conducted within 7 days before treatment) :

   1. White blood cell count ≥3.0×109/L, absolute neutrophil count ≥1.5×109/L, Hemoglobin ≥90g/L, platelet ≥75×109/L;
   2. Total bilirubin ≤1.5× upper normal value (ULN);
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5× ULN; Bilirubin ≤1.5× ULN
   4. Creatinine clearance was 44-133 mmol/L;

5. No cardiac dysfunction;

6. Life expectancy over 3 months;

7. The subject or his/her legal representative must provide written informed consent prior to conducting a special study examination or procedure.

Exclusion Criteria:

1. Previously received autologous hematopoietic stem cell transplantation;

2. Suffering from serious complications or severe infection;

3. Previous treatment with selinexor;

4. Central nervous system lymphoma was excluded;

5. A history of other malignant tumors within 5 years, excluding early tumors treated for curative purposes;

6. Patients with uncontrolled cardiovascular and cerebrovascular diseases, coagulation disorders, connective tissue diseases, serious infectious diseases, etc.;

7. HBsAg, HCV or HIV positive. Positive HBV and HCV serology is allowed, but DNA/RNA testing must be negative;

8. Left ventricular ejection fraction ≦ 50%;

9. Laboratory test value during screening;

   ① Neutrophils <1.5×109/L; Platelet <75×109/L;

   ② Bilirubin was 1.5 times higher than the normal upper limit, transaminase was 2.5 times higher than the normal upper limit;

   ③ The creatinine level is higher than 1.5 times the upper limit of normal value;

10. Other concurrent and uncontrolled medical conditions considered by the investigator would affect the patient's participation in the study;

11. Psychiatric patients or other patients known or suspected to be unable to fully comply with the study protocol;

12. Pregnant or lactating women;

13. The researcher judged that the patients were not suitable for this study.