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Marginal Zone Lymphoma: 2026 Update on Diagnosis and Management
Wan Danial Noor1,2, John F Seymour3,4, Chan Yoon Cheah1,2,5
1Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, Australia.
Disease Overview:
Marginal zone lymphoma (MZL) is a heterogeneous group of indolent mature B-cell neoplasms with classically three major subtypes: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT).
Diagnosis:
Diagnosis and disease evaluation of MZL is further advanced by the use of genomic testing and PET/CT with emerging evidence for the use of circulating tumor DNA. The RECLASS classification system proposed a hierarchical approach to classifying MZL while the FIL-NF10 investigators introduced a fourth MZL subtype, disseminated MZL. Though the prognosis of MZL varies between subtypes and stages, the MZL IPI and FLIPI24 indices can be used for prognostication.
Treatment:
Frontline treatment of MZL varies between localized disease and advanced-stage diseases. The former favor the use of local therapies such as radiotherapy and anti-microbial in certain subtypes with a selective role of rituximab monotherapy. The latter requires systemic immunotherapy ± chemotherapy with emerging data for cytotoxic-free and covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens. cBTKi and immunomodulators are established in relapsed/refractory MZL, while data for antibody-drug conjugates, T-cell engagers, and potentially CAR T-cell therapies are maturing.
