This is a prospective single arm, multi-center, phase II clinical trial to observe the efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and Prednisone) in the first-line treatment for patients with marginal zone lymphoma.

Marginal zone lymphoma (MZL) is a relatively common group of non-Hodgkin's lymphoma (NHL). The incidence rate is only inferior to diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Currently, NCCN guidelines recommend same treatment plan of FL like R-CHOP as the primary treatment for MZL. However, due to the great difference in cell origin and biological characteristics between FL and MZL, some patients can not achieve complete remission or relapse quickly after standard first-line treatment. A number of phase II clinical studies have evaluated the good efficacy of rituximab combined with chemotherapy in the treatment of MZL. Previous studies have shown that NF-κB signaling pathway is in abnormal activation state in MZL. Bortezomib, a proteasome inhibitor targeting NF-κB pathway, has a promising therapeutic prospect in relapsed and refractory MZL. The goal of our trial is to assess the efficacy and safety of VR-CAP (Bortezomib and Rituximab-Cyclophosphamide, Epirubicin and Prednisone) in the first-line treatment for patients with marginal zone lymphoma.

Inclusion Criteria:

1. Age between 18 to 70 years old (including 18 and 70)
2. Diagnosed as marginal zone lymphoma
3. No receiving chemotherapy before enrollment
4. Indications for treatment: 1) symptoms related to tumor; 2) end-organ function damage; 3) large mass; 4) continuous or rapid progress of disease; 5) patient's willingness
5. Having at least one measurable lesions
6. World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG) 0-1
7. Life expectancy no less than 3 months
8. enough main organ function
9. Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study
10. Agreeing to sign the written informed consents

Exclusion Criteria:

1. Diagnosed as central nervous system lymphoma
2. World health organization-Eastern Cooperative Oncology Group Performance tatus (ECOG) ≥2
3. Other malignant tumor history or active malignant tumor need be treated
4. Serious surgery and trauma less than two weeks
5. Systemic therapy for serious acute/chronic infection
6. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months
7. Active tuberculosis. Patients suspected of active TB need to be examined for chest X-ray, sputum and clinical symptoms and signs
8. HIV-positive, AIDS patients and untreated active hepatitis（HBV/HBV and HCV）
9. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months
10. Patients with a history of mental illness
11. Researchers determine unsuited to participate in this trial