This study aims to investigate the treatment of refractory or relapsed DLBCL with orelabrutinib and gemox. The primary endpoint is response rate (complete response rate and overall response rate), and the second endpoints are survival time (OS and PFS) and toxicities.

Inclusion Criteria:

1. Histologically confirmed relapsed or refractory Diffuse Large B-cell Lymphoma. There must be at least one evaluate able or measurable lesion that meets the Lugano criteria
2. Age beyond18 years old;
3. ECOG performance status 0-2.
4. Estimated survival time > 12 weeks.
5. Adequate first-line treatment with CD20-containing monoclonal antibody
6. DLBCL patients confirmed as non-GCB by Han's classification
7. The main organs function well, namely, the following requirements were met one week before admission: Blood routine ANC ≥ 1.5×109/L, Hb ≥ 100g/L and PLT ≥ 100×109/L; liver function were normal (total bilirubin ≤1.5×ULN, ALT and AST ≤ 2.5×ULN), renal function was normal (serum creatinine ≤1×upper limitation of normal (ULN)), and without abnormal coagulation function.
8. Pregnant women of childbearing age must have a pregnancy test (serum or urine) within 14 days before enrollment and the result is negative, and they are willing to use reliable methods of contraception during the test.
9. The subjects who volunteer to join the study and sign the informed consent form, have good compliance and cooperate with the follow-up.

Exclusion Criteria:

1. Patients with central nervous system involvement
2. Patients with Myc gene and BCL2/BCL6 gene rearrangement at the same time;
3. Patients who have received BTK inhibitor therapy in the past;
4. Patients who have received Gemox or GDP chemotherapy in the past;
5. History of other malignancy within the last 5 years prior to enrollment, except for cured basal cell carcinoma of skin, cervix in situ carcinoma and superficial bladder cancer;
6. Suffering from the following cardiovascular diseases: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (including QTc interval ≥ 450 ms for men and ≥ 470 ms for women); according to NYHA standards, grades III to IV cardiac function Incomplete, or echocardiography showed left ventricular ejection fraction (LVEF) <50%;
7. Abnormal coagulation function (INR>1.5 or prothrombin time (PT)>ULN+4 seconds or APTT>1.5 ULN), with bleeding tendency or receiving thrombolysis or anticoagulation therapy;
8. Arterial/venous thrombotic events, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, that occurred within 12 months before enrollment;
9. Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophiliacs, coagulation disorders, thrombocytopenia, hypersplenism, etc.);
10. Received major surgical operation or suffered severe traumatic injury, fracture or ulcer within 4 weeks of enrollment;
11. There are factors that obviously affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and intestinal obstruction;
12. Active infection requires antimicrobial treatment (for example, antibiotics and antiviral drugs are required, excluding chronic hepatitis B, anti-hepatitis B treatment, and antifungal drug treatment);
13. Active hepatitis B (HBV DNA ≥ 2000IU/mL or 104 copies/mL) or hepatitis C (positive hepatitis C antibody, and HCV RNA is higher than the detection limit of the analytical method);
14. Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders;
15. Participated in clinical trials of other anti-tumor drugs within 4 weeks before enrollment;
16. Received strong CYP3A4 inhibitor treatment within 7 days before enrollment, or received strong CYP3A4 inducer treatment within 12 days before participating in the study;
17. Pregnant or breastfeeding women; fertile patients who are unwilling or unable to take effective contraceptive measures;
18. The investigator judges other circumstances that may affect the conduct of clinical research and the judgment of research results.