PET/CT-Guided Maintenance Therapy in Previously Untreated MZL

Marginal zone lymphoma (MZL) is an indolent B-cell malignancy in which the value of post-induction maintenance therapy remains controversial. This is a prospective, multicenter, open-label, phase II study investigating a PET/CT-guided, response-adapted maintenance strategy in patients with newly diagnosed MZL, including its three subtypes ( extranodal MALT lymphoma, nodal MZL, and splenic MZL). A total of 45 patients will be enrolled (40 evaluable cases, assuming a 10% dropout rate).Patients aged ≥18 years with MZL confirmed per the WHO 2022 lymphoma classification, ECOG performance status 0-2, an indication for systemic treatment per NCCN guidelines, and no prior systemic therapy for MZL (excluding topical and anti-infective treatment) will be eligible. Adequate organ function is required (ANC ≥1.0×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥80 g/dL, TBIL <1.5×ULN, ALT/AST <2.5×ULN [<5×ULN with liver involvement], creatinine clearance ≥40 mL/min). Key exclusions include CNS involvement, prior or concurrent uncontrolled malignancy (except cured basal cell carcinoma, cervical carcinoma in situ, and superficial bladder cancer), significant cardiovascular disease, and coagulation abnormalities or thromboembolic events within 12 months.First-line immunochemotherapy (e.g., R-CHOP, R-CVP, or bendamustine-rituximab) will be selected by the treating physician according to routine clinical practice; the study does not intervene in treatment decisions. All patients will undergo dual-tracer PET/CT with 68Ga-Pentixafor and 18F-FDG at two mandatory time points: baseline (before first-line therapy) and end of treatment (after completion of planned first-line therapy). Both scans will be performed within 72 hours of each other at Peking Union Medical College Hospital, with randomized imaging order. Images will be independently and blindly interpreted by two experienced nuclear medicine physicians using the Lugano 2014 criteria; 18F-FDG PET/CT will be graded by the 5-point Deauville scale (score 4-5 defined as PET-positive).At the response-assessment and decision point, post-treatment 18F-FDG PET/CT results will guide the subsequent strategy: patients with a positive scan (Deauville 4-5) will receive maintenance therapy with orelabrutinib 150 mg once daily for 1 year, while patients with a negative scan (Deauville 1-3) will be followed with observation alone. The 68Ga-Pentixafor PET/CT results will be used for exploratory diagnostic-performance comparison only and will not influence treatment decisions.After the decision point, all patients will be followed every 3 months (±7 days) by clinic visit or telephone for at least 2 years, or until death, loss to follow-up, or study completion. The primary endpoint is the 2-year progression-free survival (PFS) rate. Secondary endpoints include the sensitivity, specificity, accuracy, and positive/negative predictive values of both tracers at baseline and end of treatment (with ROC analysis using pathology or clinical follow-up as the reference standard); concordance between 18F-FDG and 68Ga-Pentixafor PET/CT (kappa test); adverse events (CTCAE); and overall survival. PFS and OS will be estimated by the Kaplan-Meier method, and survival will be compared between the PET-positive and PET-negative groups using the log-rank test.