Enhancing CAR-T Cell Therapy Efficacy in B-cell Lymphoma Via Chidamide and PD-1 Inhibitor Combination.

Inclusion Criteria \- The patient must meet all of the following inclusion criteria: 1. Histologically or cytologically confirmed CD19 and/or CD22-positive large B-cell lymphoma (LBCL) according to the WHO 2016 classification, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), and related entities, with one of the following: 1. Partial response (PR) after induction therapy with a standard first-line chemotherapy regimen (e.g., R-CHOP for 4-6 cycles); or 2. Complete response (CR) after standard first-line induction therapy, but with high-risk features present at initial diagnosis. 2. Presence of high-risk features at initial diagnosis, defined as at least one of the following: 1. High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements ("double-hit" or "triple-hit") confirmed by fluorescence in situ hybridization (FISH); 2. High-grade B-cell lymphoma with 11q aberration (Burkitt-like lymphoma with 11q aberration); 3. International Prognostic Index (IPI) score of 2-5; age-adjusted IPI (aa-IPI) score of 2-3; or National Comprehensive Cancer Network-IPI (NCCN-IPI) score of 4-8; 4. CD5 positivity by immunohistochemistry; 5. Dual expression of MYC and BCL2 by immunohistochemistry (recommended thresholds: MYC ≥ 40% and BCL2 ≥ 50%); 6. TP53 mutation detected by gene sequencing; 7. Molecular subtype MCD or N1 by next-generation sequencing (NGS); 8. Relapsed/refractory B-cell lymphoma, meeting one of criteria ①-④ plus criterion ⑤: * Less than 50% tumor reduction or disease progression after ≥4 cycles of standardized chemotherapy; * Relapse within 6 months after achieving CR with standard regimen; * ≥2 relapses after CR; * Relapse after hematopoietic stem cell transplantation; * Must have received adequate prior therapy, including at least an anti-CD20 monoclonal antibody and anthracycline-containing combination chemotherapy. 3. Age 18 to 85 years, male or female. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. Expected survival of \>3 months from the date of signing informed consent. 6. Hemoglobin (HGB) ≥60 g/L (transfusion permitted). 7. Absolute neutrophil count (ANC) ≥1,000/μL and platelet count ≥45,000/μL. 8. Adequate hepatic, renal, cardiac, and pulmonary function, meeting \*\*all\*\* of the following: 1. Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN) (except for patients with Gilbert's syndrome); 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; 3. Serum creatinine (Cr) ≤1.5 × ULN \*\*or\*\* creatinine clearance (CCr) ≥60 mL/min (estimated by Cockcroft-Gault formula); 4. Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO), with no pericardial effusion and no clinically significant arrhythmias; 5. Baseline oxygen saturation by pulse oximetry \>92% on room air; 6. No clinically significant pleural effusion. Exclusion Criteria: * Patients eligible for CAR-T cell immunotherapy must \*\*NOT\*\* meet any of the following exclusion criteria: 1. Prior treatment with any form of chimeric antigen receptor (CAR) T-cell therapy or other genetically modified T-cell therapy. 2. History of severe immediate-type hypersensitivity reaction to aminoglycoside antibiotics or other drugs. 3. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics. (Active HBV infection is defined as meeting \*\*all\*\* of the following: a) HBV DNA ≥ 2000 IU/mL; b) ALT ≥ 2 × upper limit of normal (ULN); c) hepatitis not attributable to other causes such as the underlying disease or medications. Patients with active HBV at initial diagnosis who achieve non-active HBV status after adequate anti-HBV treatment may be eligible under continued effective anti-HBV therapy.) 4. Non-hematologic malignancy-related hepatic or renal impairment, including any of the following: ALT \> 3 × ULN, AST \> 3 × ULN, total bilirubin (TBIL) \> 2 × ULN, or creatinine clearance \< 30 mL/min. 5. History of myocardial infarction, percutaneous coronary intervention (including coronary angioplasty or stenting), unstable angina, active arrhythmia, or other clinically significant cardiovascular disease within the past 12 months. 6. Any other serious medical condition that, in the opinion of the investigator, may interfere with the study treatment or increase risk to the patient (e.g., poorly controlled diabetes, active peptic ulcer disease, severe respiratory or circulatory disease, severe autoimmune disease, congenital immunodeficiency, uncontrolled severe infection, or other conditions with high risk of clinical deterioration). 7. History of severe immediate-type hypersensitivity reaction to any medication required during the treatment process, or history of severe allergy to biologics (including antibiotics). 8. Female patients who are pregnant or breastfeeding (preconditioning chemotherapy regimen poses potential risk to the fetus or infant). 9. In the opinion of the investigator, the patient is unlikely to comply with all required study visits, procedures, or long-term follow-up; has poor willingness or ability to participate and cooperate fully; or has insufficient compliance (as judged by the patient and/or family). 10. History of other malignancy, unless the patient has been disease-free and has received no antitumor therapy for at least 3 years (exceptions: non-melanoma skin cancer, and carcinoma in situ of the cervix, bladder, or breast). 11. Receipt of a live vaccine within 6 weeks prior to initiation of the preconditioning regimen. 12. Major surgery (excluding lymph node biopsy) within the past 14 days, or anticipated need for major surgery during the treatment period. 13. Any other serious physical or psychiatric illness, or clinically significant laboratory abnormality, that may increase the risk associated with study participation, interfere with the interpretation of study results, or render the patient unsuitable for participation in the opinion of the investigator.