The treatment landscape of B-cell non-Hodgkin lymphomas is rapidly evolving. However, few advances have occurred in marginal zone lymphoma (MZL), with a single US Food and Drug Administration–approved agent impacting the treatment landscape. Multiple factors are associated with this slower pace of progress, with a lower MZL incidence representing a significant factor. Pivotal randomized indolent lymphoma clinical trials analyzed MZL subsets without the appropriate power to capture differences between treatment arms. Furthermore, the current Lugano classification may not fully capture the presentation or treatment responses of some subtypes, preventing access to clinical trials and limiting an efficacy assessment across the disease spectrum. Thus, current MZL treatment is largely informed by single-arm studies with relatively empiric treatment sequencing among available agents. Although frontline strategies in early and advanced-stage MZL can achieve prolonged disease control, few options exist in the relapsed/refractory setting capable of achieving similar results. Emerging data demonstrate the encouraging efficacy of CD3×CD20 bispecific antibodies and antibody-drug conjugates in achieving deep responses, as well as the potential of circulating tumor DNA in risk stratification and molecular response monitoring. Compounding all these considerations, it is essential to recognize MZL as a heterogeneous group of diseases characterized by unique biology, clinical presentation, treatment response, toxicity, and survival. Nonetheless, a common characteristic across MZL subtypes is their general indolent disease course, emphasizing the need to incorporate patient-centered assessment in clinical trials to better inform the decision-making process.
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MARGINAL ZONE LYMPHOMA|
January 8, 2026
The treatment of marginal zone lymphoma Available to Purchase
Juan Pablo Alderuccio,
Juan Pablo Alderuccio
1Division of Hematology, Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
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Ariela Noy
Ariela Noy
2Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
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Blood (2026) 147 (2): 115–126.
Article history
Submitted:
March 24, 2025
Accepted:
June 15, 2025
First Edition:
July 15, 2025
Connected Content
A related article has been published:
Drug development in MZL: caring for the forgotten child
A related article has been published:
The biology of marginal zone lymphoma subtypes: challenge and relevance of classification
A commentary has been published:
Introduction to a review series on marginal zone lymphoma: reclaiming the afterthought
Citation
Juan Pablo Alderuccio, Ariela Noy; The treatment of marginal zone lymphoma. Blood 2026; 147 (2): 115–126. doi: https://doi.org/10.1182/blood.2024028269
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January 8 2026
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