This study is trying to explore the mechanism of R-CHOP regimen or tucidinostat plus R-CHOP (CR-CHOP) regimen in the treatment of BCL2/MYC protein double expressor lymphoma.

Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase inhibitor. This study is trying to explore the mechanism of R-CHOP regimen or tucidinostat plus R-CHOP (CR-CHOP) regimen in the treatment of BCL2/MYC protein double expressor lymphoma. We will retain the hematoxylin and eosin (HE) -stained slides of tumor tissue, immunohistochemical staining slides for BCL2 and MYC, as well as FFPE (Formalin Fixed Paraffin Embedded) tissues. We will conduct biological tests via digital pathology and DNA sequencing, aiming to uncover the pathogenic mechanism of double expressor lymphoma and the potential therapeutic targets of CR-CHOP regimen.

Inclusion Criteria:

• Each potential subject must satisfy all of the following criteria to be enrolled in the study.

Male or female, age ≥ 18 years and ≤80 years. No prior treatment for diffuse large B cell lymphoma(DLBCL), including hemotherapy, immunotherapy; radiotherapy (excluding local radiotherapy); monoclonal antibody therapy; surgical treatment (excluding biopsy) Histological or cytological confirmation of DLBCL CD20-positive DLBCL; Myc≥40% as well as Bcl-2≥50% through immunohistochemistry; Not with double (BCL-2 and c-MYC gene rearrangement) or triple (BCL-2, BCL-6, and c-MYC gene rearrangement) hit by FISH.

The verification of DLBCL will be based on local pathology report.15-20 unstained slides must be sent to the central laboratory for retrospective confirmation.

4.At least one positive lesion according to the Lugano Classification by fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography(CT).

5.Lymphoma International PrognosisIndex (IPI) score of 2,3,4. 6.Eastern Cooperative Oncology Group performance status grade of 0, 1, or 2. 7.Laboratory criteria are as follows except that caused by lymphoma assessed by the investigator (without receiving any supportive treatment for the following parameters within 2 weeks from the last dose prior to study entry):

(1)Hematology values:Hemoglobin (Hb)≥90g/L ; Absolute neutrophil count (ANC) ≥1.5×109/L ; platelets ≥90×109/L (2)Biochemical values: Serum creatinine ≤1.5×upper limit of normal(ULN); Total bilirubin ≤1.5 × ULN; Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) ≤2.5×ULN(ALT,AST≦5×ULN if liver involved).

8.Expected survival≥6 months. 9.All patients must have signed an informed consent document.

Exclusion Criteria:

• Any potential subject who meets any of the following criteria will be excluded from participating in the study.

Presence of CNS involvement. Patients with primary DLBCL of the central nervous system (CNS),or secondary lymphoma of the central nervous system, or Primary mediastinal (thymic) large B-cell lymphoma, or Primary effusion lymphoma, or B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma, or Primary cutaneous DLBCL, leg type, or indolent lymphoma, or Burkitt lymphoma, or EBV-positive mucocutaneous ulcer, or DLBCL associated with chronic inflammation, or Lymphomatoid granulomatosis, or Intravascular large B-cell lymphoma, or ALK-positive large B-cell lymphoma, or Plasmablastic lymphoma, or HHV8-positive DLBCL, NOS, or primary testicular DLBCL.

Patients with transformed lymphoma. History of organ transplantation or hematopoietic stem cell transplantation. Patients planned for autologous or allogeneic transplant as consolidation in first line.

Patients with any other malignancy, except patients with a history of curatively treated basal or squamous cell carcinoma or in situ carcinoma of the cervix at any time prior to the study are eligible.

Prior treatment with cytotoxic drugs for another condition (e.g., rheumatoid arthritis) or prior use of an anti-CD20 antibody within 5 years of the start of Cycle 1.

Prior use of any monoclonal antibody within 3 months of the start of Cycle 1. Any investigational therapy within 3 months prior to the start of Cycle 1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.

Contraindication to any of the individual components of CHOP.

Corticosteroid use > 30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control:

Patients receiving corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to randomization (Cycle 1, Day 1).

If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisone 100 mg or equivalent could be given for a maximum of 5 days, but all tumor assessments must be completed prior to start of glucocorticoid treatment.

13.Ongoing serious central nervous system disease or peripheral neuropathy, such as progressive multifocal leukoencephalopathy.

14.Have uncontrolled or significant cardiovascular disease, including: Grade II or higher Congestive heart failure, unstable angina pectoris, myocardial infarction (New York Heart Association Functional Classification ) within 6 months prior to study entry; or arrhythmia requiring treatment, or Left Ventricular Ejection Fraction (LVEF) < 50% during screening stage.

Primary cardiomyopathy (dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al).

History of significant QT interval prolongation, or Corrected QT Interval QTc≥450ms(male), QTc≥470ms（female）at screening.

Symptomatic coronary heart disease requiring treatment. Any other cardiovascular disease which is inappropriate for the study according to investigators' judgment.

15.History of interstitial lung disease(ILD), or with ongoing signs and symptoms by CT or MRI at the time of screening.

16.Patients with factors that could affect oral medication (such as dysphagia, chronic diarrhea, intestinal obstruction etc), or undergone gastrectomy.

17.History of deep vein thrombosis or pulmonary embolism. 18.History of active bleeding within 2 months prior to the start of Cycle 1;or patients receiving anticoagulation therapy; or patients with evidence of bleeding potential according to investigators' judgment ( esophageal varices, active ulcer, or fecal occult blood test positive etc. ). Patients with bleeding led by lymphoma according to investigators' judgment are eligible.

19.6 weeks or less from the last major surgery that involved crucial organs, or with any other factors impede postoperative recovery according to investigators' judgment.

20.Known active infection, or active and uncontrolled hepatitis B infection(HBV), hepatitis C Virus(HCV), human immunodeficiency virus (HIV)/AIDS (Acquired Immune Deficiency Syndrome), or any other serious infection. (active infection defined as any major episode of infection requiring systemic treatment; Patients with occult or prior HBV may be included if HBV DNA is undetectable.) 21.Any mental or cognitive disorder, that would impair the ability to understand the informed consent document, or limit compliance with study requirements/ treatment.

22.Drug or alcohol abuse. 23.Women of childbearing potential and men who are sexually active not willing to practice a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials.These restrictions apply for 12 months after the last dose of rituximab or 12 weeks after the last dose of study drug, whichever is later. Pregnancy or lactation.

24.Any other condition which is inappropriate for the study according to investigators' judgment.

Patients with accessible tissue samples were selected from a phase III study of tucidinostat in combination with R-CHOP in patients with newly diagnosed double expressor DLBCL (NCT04231448).