Rituximab Maintenance Versus Observation After R2 Induction in Previously Untreated Marginal Zone Lymphoma

• Rituximab (Drug): Patients will receive R2 induction therapy consisting of rituximab and lenalidomide. Patients who achieve complete response or partial response after induction will receive rituximab maintenance every 8 weeks for up to 2 years.
• Observation (Other): Patients will receive R2 induction therapy consisting of rituximab and lenalidomide. Patients who achieve complete response or partial response after induction will undergo observation without maintenance anti-lymphoma therapy.

Primary outcomes

• 2-year progression-free survival rate [At 2 years after randomization]: The 2-year progression-free survival rate is defined as the proportion of patients who are alive without disease progression at 2 years after randomization.

Secondary outcomes

• Complete response rate [Up to 24 months after randomization]: Complete response rate is defined as the proportion of patients who achieve complete response according to the Lugano 2014 criteria during the maintenance or observation period.
• Overall response rate [Up to 24 months after randomization]: Overall response rate is defined as the proportion of patients who achieve complete response or partial response according to the Lugano 2014 criteria during the maintenance or observation period.
• Duration of response [Up to 24 months after randomization]: Duration of response is defined as the time from the first documented complete response or partial response to disease progression, relapse, or death from any cause, whichever occurs first.
• Overall survival [Up to 24 months after randomization]: Overall survival is defined as the time from randomization to death from any cause.
• Event-free survival [Up to 24 months after randomization]: Event-free survival is defined as the time from randomization to disease progression, relapse, initiation of new systemic anti-lymphoma therapy, or death from any cause, whichever occurs first.
• Disease-free survival [Up to 24 months after randomization]: Disease-free survival is defined as the time from the first documented complete response to disease relapse, progression, or death from any cause, whichever occurs first.
• Incidence of progression of disease within 24 months [Within 24 months from the start of induction therapy]: POD24 is defined as the proportion of patients who experience disease progression, relapse, or death from any cause within 24 months from the start of frontline induction therapy.
• Patient-reported outcomes [Up to 24 months after randomization]: Patient-reported outcomes will be assessed using the EORTC QLQ-C30 questionnaire.
• Incidence of adverse events and serious adverse events [Up to 30 days after the last study treatment or during follow-up as clinically indicated]: The incidence and severity of adverse events and serious adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Able to understand and voluntarily sign the informed consent form.
* Age ≥18 years.
* Histologically confirmed CD20-positive marginal zone lymphoma, including extranodal, splenic, or nodal subtypes.
* Considered unsuitable for or unable to tolerate standard chemotherapy.
* Previously untreated with systemic anti-lymphoma therapy.
* Measurable or evaluable disease according to Lugano 2014 criteria.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Adequate organ function.

Exclusion Criteria:

* History of other malignancies that may interfere with study assessment.
* Central nervous system involvement by lymphoma.
* Known HIV infection or active hepatitis B/C infection.
* Active or uncontrolled infection.
* Gastrointestinal condition that may interfere with oral administration or absorption of study treatment.
* Pregnancy or breastfeeding.