Marginal Zone Lymphoma

P2, N=144, Not yet recruiting, Sun Yat-sen University

P1, N=42, Active, not recruiting, Acepodia Biotech, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jul 2026

P2, N=37, Suspended, David Bond, MD | Recruiting --> Suspended

In the field of imaging, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has inherent limitations in MZL, whereas novel targeted tracers like C-X-C motif chemokine receptor type 4 (CXCR4) PET/CT show improved lesion detection rates and preliminary prognostic value, and imaging omics holds promise for non-invasively revealing tumor heterogeneity. This review systematically summarizes the current status and shortcomings of these prognostic factors, and proposes that future efforts should focus on integrating clinical, molecular genetics, imaging, and multi-omics data, and leveraging artificial intelligence technology to construct multicenter-validated, multidimensional prognostic models, so as to advance precision risk stratification and individualized treatment for MZL.

P1/2, N=190, Active, not recruiting, ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) | Trial completion date: Sep 2026 --> Sep 2027 | Trial primary completion date: Sep 2026 --> Sep 2027

P1, N=85, Recruiting, Exscientia AI Ltd., a wholly owned subsidiary of Recursion Pharmaceuticals, Inc. | N=50 --> 85

P2, N=138, Not yet recruiting, SWOG Cancer Research Network

AMP-mediated killing, driven by membrane disruption and non-apoptotic death pathways, bypassed conventional resistance mechanisms, suggesting therapeutic potential in relapsed/refractory disease. Our findings highlight natural AMPs as promising candidates for development in drug-resistant MZL, warranting further optimization and preclinical validation.

In this contemporary POL series, clinicopathologic heterogeneity was prominent, and laboratory profiles frequently overlapped with ovarian malignancy work-up. Outcomes may be favorable among patients receiving timely, subtype-appropriate systemic treatment.

P=N/A, N=10, Completed, British Columbia Cancer Agency | Not yet recruiting --> Completed | N=30 --> 10

[68Ga]Ga-PentixaFor PET/CT significantly outperforms [18F]FDG in initial staging of MZL and has a substantial impact on clinical management. Importantly, dual-tracer imaging shows potential as a novel, non-invasive biomarker for in vivo phenotypic characterization, which is associated with early therapeutic outcomes and the identification of high-risk patients.

Case 1 was a 65-year-old woman diagnosed in 2017 with SMZL and treated with rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisone (or prednisolone) (R-CHOP), achieving complete remission, who presented nine years later with recurrent hyperlymphocytosis at 10.8 × 109/L with villous appearance, massive splenomegaly, and systemic symptoms...The patient was treated with rituximab-bendamustine and achieved complete remission...Rituximab monotherapy was followed by rapid improvement, with normalization of the lymphocyte count to 2.13 × 109/L and regression of splenomegaly from the first cycle. These observations highlight the importance of combining lymphocyte immunophenotyping and bone marrow aspiration in isolated splenomegaly with villous lymphocytes on blood smear to avoid underdiagnosis of this new histopathological entity and therefore guide therapeutic management in the absence of guidelines.