Chidamide, Lenalidomide, and Rituximab in Newly Diagnosed Elderly/unFit DE-DLBCL

• Histopathologically confirmed, previously untreated DLBCL;
• Age ≥70 years, or ≥60 years with comorbidities (including reduced left ventricular ejection fraction, history of myocardial infarction [>6 months prior to enrollment], exertional angina, arrhythmia [Grade ≤2], hypertension or diabetes requiring treatment), or ECOG PS ≥2 deemed ineligible for standard chemotherapy;
• At least one measurable lesion, defined as: Nodal lesion: Longest diameter >1.5 cm, or Extranodal lesion: Longest diameter >1.0 cm, with two perpendicular dimensions accurately measurable;
• ECOG PS ≤3;
• Estimated life expectancy ≥3 months
• MYC and BCL2 protein co-expression confirmed by immunohistochemistry (double-expressor lymphoma)
• Voluntary participation; full understanding of the study with signed informed consent; willingness and ability to comply with all study procedures

Exclusion Criteria:

• Pregnant or lactating women, and patients of childbearing potential unwilling to use contraception;
• Recipients of organ transplantation;
• Uncontrolled coagulopathy or active bleeding;
• Uncontrolled cardiocerebrovascular diseases (including LVEF \<50%), connective tissue diseases, or severe active infections;
• Major organ surgery within 6 weeks prior to screening;
• Laboratory abnormalities at screening (unless lymphoma-related): Neutrophils \<1.5×10⁹/L; Platelets \<80×10⁹/L (\<50×10⁹/L if bone marrow involvement); Liver dysfunction: Total bilirubin >1.5×ULN, ALT/AST >2.5×ULN (or >5×ULN with liver involvement); Renal dysfunction: Serum creatinine >1.5×ULN;
• HBV infection: HBsAg-positive patients: Eligible if HBV DNA \<10³ IU/mL; HBsAg-negative but HBcAb-positive (regardless of HBsAb status): Eligible if HBV DNA \<10³ IU/mL;
• HIV infection;
• Central nervous system lymphoma involvement;
• Concurrent antitumor therapy (for lymphoma or other malignancies);
• Substance abuse or chronic alcoholism affecting outcome evaluation;
• Psychiatric disorders or other conditions compromising protocol compliance;
• Concurrent use of strong/moderate CYP3A4 inhibitors/inducers: Excluded if taken within 7 days prior to treatment (or \<5 half-lives);
• Inability to swallow capsules or significant gastrointestinal dysfunction (e.g., malabsorption, bariatric surgery, IBD, bowel obstruction);
• Other uncontrolled conditions deemed by investigators to: Jeopardize patient safety; Interfere with drug absorption/metabolism; Pose excessive risk to study outcomes