Lenalidomide Combined With R-CHOP(R2-CHOP) in Newly Diagnosed Double-expressor Diffuse Large B-Cell Lymphoma Patients

Double expressor lymphoma is a subtype of diffuse large B-cell lymphoma defined as having increased expression of MYC and BCL-2 by immunohistochemistry. Patients with double-expressor lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of progression and recurrence. The investigators conducted this study to evaluate the efficacy of lenalidomide combined with R-CHOP (R2-CHOP) in newly diagnosed double-expressor, untreated Diffuse Large B-Cell Lymphoma patients (DLBCL). Lenalidomide is the second-generation immunomodulatory drug, and its anti-tumor mechanism may involve immunomodulatory, antiinflammatory, and antiangiogenic effects and suppression of tumor necrosis factor-alpha (TNF-α) from peripheral blood mononuclear cells. In this phase II study, the investigators are aiming to explore lenalidomide combined with R-CHOP (R2-CHOP) in newly diagnosed double-expressor Diffuse Large B-Cell Lymphoma patients (DLBCL), in order to find a potential promising way to treat this kind of disease.

Inclusion criteria

• Age range 18-75 years old
• Eastern Cooperative Oncology Group performance status 0 to 2;
• Newly diagnosed, untreated, histological confirmed diffuse large B cell lymphoma, and Myc≥40% as well as Bcl-2≥50% through immunohistochemistry；
• Measurable disease was defined as at least one lesion ≥1.5 cm in length-diameter and ≥1.0cm in short-diameter by CT or MRI.
• White blood cell ≥ 3.5×109/L, absolute neutrophil count ≥ 1.5×109/L，platelet ≥ 80×109/L，hemoglobin ≥ 90 g/L. If abnormal factors of peripheral blood caused by bone marrow or spleen involvement of lymphoma, whether to enroll depends on the judgment of researchers
• Total bilirubin < 1.5×upper limit of normal(ULN), ALT and AST < 1.5× ULN
• serum creatine <1.5×ULN, and creatinine clearance rate (CCR) ≥ 40 ml/min
• Ultrasonic cardiogram or nuclide cardiac function showed left ventricle ejection fraction ≥ 50%
• Women of childbearing potential and men who are sexually active are consent to practicing a highly effective method of birth control. Women of childbearing potential must have a negative serum β-hCG within 2 weeks of enrollment
• Patients have written informed consent to participate in the study.

Exclusion criteria

• Prior sever allergy to humanized or mouse derived monoclonal antibody. Unable to receive either lenalidomide or R-CHOP background chemotherapy.
• History of myocardial diseases, such as unstable angina pectoris, acute myocardial infarction within 6 months of enrollment, congenital heart failure NYHA III/IV
• Particular kind of DLBCL，such as primary mediastinal/thymic B-cell lymphoma, EBV positive DLBCL, primary cutaneous large B lymphoma, leg type.
• Presence of CNS involvement
• Having surgeries ≥ grade 2 within 3 weeks of enrollment.
• History or now in the treatment process of other malignancies except cured basal cell carcinoma of skin (melanoma not included), and carcinoma in-situ of uterine cervix.
• More than grade 3 neurotoxicity within 2 two weeks of enrollment
• Receiving any treatment for lymphoma except short use of corticosteroid (no more than 10 days)
• History of deep vein thrombosis or pulmonary embolism within 12 months of enrollment
• Unable or reject to receive antithrombotic treatment
• Presence of active HBV infection (HBsAg positive and HBV-DNA≥ 104), HCV infection, acquired and congenital immunodeficiency diseases include but not limited to HIV
• Pregnant or lactating women
• Previously received organ transplant
• Serious uncontrolled infection
• Having contraindications to the use of large doses of hormone, such as uncontrolled hyperglycemia, gastric ulcer, mental disorder.
• Severe neurol of mental illness, including dementia and epilepsy.
• Drug abuse, medical, psychological or social conditions which may interfering with subjects' participation in the study or evaluation of the results
• Patients considered unsuitable to participate in the study by the researchers