This phase 2 trial studies the efficacy and safety of zanubrutinib plus rituximab followed by R-DHAOx (rituximab, dexamethasone, cytarabine and oxaliplatin) regimen then maintenance with zanubrutinib for newly-diagnosed Mantle Cell Lymphoma (MCL).

Inclusion Criteria:

• Histologically confirmed CD20 positive mantle cell lymphoma;
• Patients with MCL-related symptomatic and need immediate therapy; Include any of the following: (1) Blastoid variant (2) Pleomorphic variant (3) Ki-67 ≥30% (4) Bulky mass > 7 cm or ≥2 tumors, each ≥5 cm in diameter (5) Mutations in TP53, c-MYC or NOTCH genes (6) Size of spleen ≥20 cm (7) Lymphoma B symptoms (8) Mantle Cell International Prognostic Score (MIPI) > 3 (9) Lymphoma threatening organ function (10) Elevated lactate dehydrogenase (11) Peripheral blood white blood cell > 50×10^9/L (12) Pancytopenia due to bone marrow involvement (13) Pain due to lymphoma;
• Patients received no prior anti-lymphoma treatment;
• At least one evaluable lesion according to 2014 Lugano criteria;
• Ann Arbor stage II-IV;
• Eastern Cooperative Oncology Group (ECOG) of 0-2;
• Life expectancy > 3 months;
• Able to participate in all required study procedures;
• Proper functioning of the major organs: 1) The absolute value of neutrophils (>1.5×10^9/L); 2) platelet count (> 75×10^9/L); 3) Hemoglobin (> 80 g/L); 4) Serum creatinine <1.5 times Upper Limit Normal (ULN) ; 5) Serum total bilirubin < 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) < 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) < 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range at screening time);

Exclusion Criteria:

• Involvement of central nervous system (CNS)
• Patients with Hemophagocytic syndrome;
• Patients with active bleeding, bleeding tendency or require anticoagulation treatment;
• Patients require treatment with strong CYP3A inhibitors;
• Uncontrolled active infection, with the exception of tumor-related B symptom fever;
• History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known;
• Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 1000 IU/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 1000 IU/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;
• Diagnosed with or receiving treatment for malignancy other than lymphoma;
• Pregnant or breastfeeding women;
• Other researchers consider it unsuitable for patients to participate in this study.