To evaluate the efficacy and safety of CAGM regimen in R/R DLBCL patients and to provide a safe and more effective approach for R/R DLBCL patients.

The study will start with an initial 2 cycles of induction therapy with CAGM containing chidamide, azacitidine, obinutuzumab and mitoxantrone liposome, orelabrutinib and rituximab，following imaging examinations to evaluate response rates. For patients feasible to CAR-T/ASCT, sequential CAR-T/ASCT treatment was given. For patients who were unable to undergo CAR-T/ASCT, 4 cycles of CAGM immunochemotherapy were carried out. Efficacy and safety of CAGM regimen in R/R DLBCL will be evaluated.

Inclusion Criteria:

1. Age ≥ 18 years.
2. At least one measurable lesion，measurable lymph nodes or masses of at least 15 millimeter (mm).
3. Histopathologically confirmed DLBCL.
4. Diseases refractory to first-line treatment (including CD20 monoclonal antibody and anthracycline) or relapsed after the last treatment.
5. Life expectancy > 3 months.
6. Appropriate organ function: Cardiac function: cardiac ejection fraction ≥50%; Liver function: alanine aminotransferase and aspartate aminotransferase ≤3 times the upper limit of normal; Renal function: serum creatinine clearance ≥30 mL/min; Lung function: SPO2>91% without oxygen;
7. Adequate bone marrow reserve: Hemoglobin ≥8 g/dL; Platelet count ≥75×10^9/L; Absolute neutrophil value ≥1.0×10^9/L; Platelet count ≥50×10^9/L, absolute neutrophil value ≥0.75×10^9/L if there is bone marrow invasion.
8. The patient has the ability to understand and is willing to provide written informed consent.
9. Agreement to practice birth control from the time of enrollment until the follow-up period of the study.

Exclusion Criteria:

1. Severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal);
2. Structural heart disease, leading to clinical symptoms or abnormal cardiac function (NYHA ≥ grade 2);
3. Uncontrolled active infection;
4. Concurrent presence of other tumors requiring treatment or intervention;
5. Current or expected need for systemic corticosteroid therapy;
6. Pregnant or lactating women.
7. Other psychological conditions that prevent patients from participating in the research or signing the informed consent.
8. In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or does not meet the requirements for participation in the study.