CD20 Monoclonal Antibody-Based First-Line Therapy in Treatment-Naive Marginal Zone B-Cell Lymphoma

Risk-Stratified Real-World Multicenter Study of the Efficacy and Safety of CD20 Monoclonal Antibody-Based First-Line Therapy in Treatment-Naive Marginal Zone B-Cell Lymphoma

This is a multicenter, real-world study on first-line CD20 monoclonal antibody-based regimens for treatment-naive marginal zone B-cell lymphoma based on risk stratification. The primary objective is to evaluate the efficacy and safety of the "BR", "R2", and "OR2" treatment regimens in treatment-naive MZL patients receiving first-line CD20 monoclonal antibody-based therapy stratified by risk.

Study Overview

• Status: Not yet recruiting
• Conditions: MZL
• Intervention / Treatment: Drug: R2/BR/OR2

• Study Type: Observational
• Enrollment (Estimated): 131

Contacts and Locations

• Study Contact: Name: Keshu Zhou; Phone Number: 136 7490 2391; Email: dr_zkshu23810@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hospital

Description

Inclusion Criteria:

• Histologically confirmed marginal zone B-cell lymphoma (MZL) in accordance with the 2016 WHO classification;
• Age ≥ 18 years, with no gender restriction;

• Patients with MZL requiring systemic therapy, including but not limited to:

  1. Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), HP-positive or HP-negative, with progression/relapse after local therapy (including surgery, radiotherapy, and anti-Helicobacter pylori treatment);

  2. Non-gastric MALT lymphoma:

     Patients with Ann Arbor Stage I-II disease with progression/relapse after local therapy (including surgery, radiotherapy, etc.); Patients with newly diagnosed Ann Arbor Stage III-IV disease meeting the GELF criteria as recommended by the NCCN Guidelines;

  3. Splenic marginal zone lymphoma (SMZL):

     Patients with progression/relapse after local therapy (including splenectomy, antiviral therapy in HCV-positive patients, etc.); Or newly diagnosed with: progressive or painful splenomegaly, symptomatic or progressive cytopenia, defined as Hb < 100 g/L, PLT < 80 × 10⁹/L, or absolute neutrophil count (ANC) < 1.0 × 10⁹/L;

  4. Nodal marginal zone lymphoma (NMZL):

Patients with Ann Arbor Stage I-II disease with progression/relapse after local therapy (including surgery, radiotherapy, etc.); Patients with newly diagnosed Ann Arbor Stage III-IV disease meeting the GELF criteria as recommended by the NCCN Guidelines;

• ECOG performance status 0, 1, or 2 (Appendix 4);
• Adequate general condition, with a life expectancy > 3 months;
• Adequate bone marrow function (except for cytopenia caused by the underlying disease), liver function, and renal function;
• Commitment to comply with study procedures and cooperate throughout the entire study period;
• The patient or his/her legally authorized representative must provide written informed consent prior to any study-specific tests or procedures;
• For women of childbearing potential: agreement to use adequate contraceptive measures during study treatment and for at least 1 year after treatment completion.Men must agree to practice abstinence or use barrier contraception.

Exclusion Criteria:

• Histological transformation to high-grade lymphoma.
• Known central nervous system (CNS) involvement by lymphoma or evidence of CNS disease.
• Prior systemic therapy, including immunotherapy, chemotherapy, or targeted therapy.
• Prior autologous stem cell transplantation, or allogeneic tissue / solid organ transplantation.
• History of other invasive malignancies that were not treated with curative intent or for which anticancer treatment (including hormone therapy for breast or prostate cancer) was administered within the past 3 years.
• Presence of uncontrolled cardiovascular or cerebrovascular diseases (e.g., New York Heart Association class III or IV heart failure, arrhythmia, myocardial infarction, stroke, or intracranial hemorrhage), coagulation disorders, connective tissue diseases, severe infectious diseases (including active tuberculosis), or other similar conditions.
• Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection (positive result by polymerase chain reaction [PCR]).Seropositivity is permitted; patients with HBV DNA < 10³ IU/mL may be enrolled. HCV RNA must be negative.
• Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment.Receipt of live attenuated vaccines, including influenza vaccines, is prohibited during the study period.
• Requirement for continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

R2/BR/OR2; For patients with low-risk marginal zone B-cell lymphoma (MZL-IPI score: 0-2 points), the "R2" regimen is preferred as the first-line treatment. If the patients are unable to tolerate or are not suitable for the R2 regimen, the "BR" regimen may be administered as an alternative.. For patients with high-risk marginal zone B-cell lymphoma (MZL-IPI score: 3-5 points), the "R2" or "OR2" regimen is administered for first-line treatment.

Drug: R2/BR/OR2; R2 regimen: 28-day cycle Rituximab was administered at a dose of 375 mg/m² via intravenous infusion on Day 1 of each cycle (Cycles 1-6); Lenalidomide was given orally at 20 mg per day from Day 1 to Day 21 of each cycle (Cycles 1-6). BR regimen: 28-day cycle Rituximab was administered at a dose of 375 mg/m² via intravenous infusion on Day 1 of each cycle (Cycles 1-6); Bendamustine was given via intravenous infusion at 70 mg/m² on Day 1 and Day 2 of each cycle (Cycles 1-6). OR2 regimen: 21-day cycle Rituximab was administered at a dose of 375 mg/m² via intravenous infusion on Day 1 of each cycle (Cycles 1-6); Lenalidomide was given orally at 20 mg per day from Day 2 to Day 11 of each cycle (Cycles 1-6); Orelabrutinib was administered orally at 150 mg per day for 2 years .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate（CRR）	The proportion of patients who achieved complete remission (CR) after the completion of treatment was evaluated in accordance with the revised criteria for the assessment of malignant lymphoma efficacy proposed at the 2014 Lugano Conference	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year progression-free survival (PFS) rate	The percentage of patients who remained alive and free of disease progression at 2 years after study entry, whichever occurred first	2 years
2-year overall survival (OS) rate	The percentage of patients who remained alive at 2 years after study entry.	2 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2025-726-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No