MZL-IPI Risk-adapted Targeted Therapy in Untreated MZL

Inclusion criteria

• 1. Histopathologically confirmed CD20-positive marginal zone lymphoma (according to the 2016 WHO classification).

• Age ≥ 18 years old, regardless of gender. 3. MZL patients requiring systemic treatment, including but not limited to:
• Helicobacter pylori (HP)-positive or HP - negative gastric mucosa extranodal marginal zone lymphoma (MALT) patients with progression/relapse after local treatment (including surgery, radiotherapy, and anti - Helicobacter pylori treatment).
• Non - gastric MALT patients with Ann Arbor stage I - II who have progression/relapse after local treatment (including surgery, radiotherapy, etc.), or untreated patients with Ann Arbor stage III - IV who meet the GELF criteria recommended by the NCCN guidelines.
• Splenic marginal zone lymphoma (SMZL) patients with progression/relapse after local treatment (including splenectomy, antiviral treatment for HCV - positive patients, etc.), or untreated patients meeting the criteria of progressive or painful splenomegaly, symptomatic or progressive cytopenia such as HB < 100g/L, PLT < 80×10⁹/L, absolute neutrophil count (ANC) < 1.0×10⁹/L.
• Nodal marginal zone lymphoma (NMZL) patients with Ann Arbor stage I - II who have progression/relapse after local treatment (including surgery, radiotherapy, etc.), or untreated patients with Ann Arbor stage III - IV who meet the GELF criteria recommended by the NCCN guidelines.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 5. Life expectancy of at least 3 months. 6. The patient has adequate bone marrow (except those caused by MZL), liver and kidney functions.

• Able to comply with the research procedures and cooperate in the implementation of the entire research process; 8. Written informed consent; 9. Women with fertility agree to take appropriate measures to avoid pregnancy during the treatment period until at least one year after the end of treatment; Men agree to maintain abstinence or use barrier contraception.

Exclusion criteria

• 1. Histologically transformed into high-grade lymphoma. 2. Known central nervous system involvement of MZL. 3. Previous systemic treatment including immunotherapy, chemotherapy or targeted drugs.

• Previous autologous stem-cell transplantation or allogeneic tissue/solid organ transplantation.

• History of other invasive cancers within the past 3 years that have not received curative treatment or are still receiving anti-cancer treatment (including hormonal therapy for breast or prostate cancer).

• Complicated with uncontrolled cardiovascular and cerebrovascular diseases (such as New York Heart Association-defined grade 3 or 4 heart failure, arrhythmia, myocardial infarction, stroke, or intracranial hemorrhage), coagulation - disorder diseases, connective tissue diseases, severe infectious diseases (including active pulmonary tuberculosis), etc.

• Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection (positive result shown by polymerase chain reaction [PCR]). Serological antibody - positive is allowed if HBV DNA < 10³ IU/ml; HCV RNA test must be negative.

• Vaccinated with live attenuated vaccines within 4 weeks before starting investigational treatment. During the study, patients are prohibited from receiving live attenuated vaccine inoculations, including influenza vaccines.

• Requiring continuous treatment with potent and moderate-effect CYP3A inhibitors or CYP3A inducers.

• Unable to swallow capsules or having diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial or complete intestinal obstruction.

• Psychiatric patients or other patients known or suspected to be unable to fully comply with the study protocol.

• Pregnant or lactating women. 13. Other concurrent and uncontrolled medical conditions that, in the investigator's opinion, will affect the patient's participation in the study.