The article discusses challenges in treating Marginal Zone Lymphoma (MZL), emphasising new targeted therapies like zanubrutinib for improved efficacy. It highlights the evolving landscape of MZL treatment, addressing issues of recurrence and refractory cases.

Marginal zone lymphomas (MZL) are a group of indolent B-cell non-Hodgkin's lymphomas (NHL) which arise from the marginal zone in the lymph tissue.[1] Making up about 8% of all NHL cases, MZL is not insignificant. Historically, MZL has often been treated like other B-cell lymphomas, for which there is no standard treatment.[2]

Diagnosis of MZL

MZL is comprised of three distinct groupings: extranodal MZL (EMZL), which is often called MALT lymphoma; splenic MZL (SMZL), with or without villous lymphocytes; and nodal MZL (NMZL), with or without monocytoid B cells. EMZL is the most common, accounting for two-thirds of MZL cases, and NMZL is the rarest, accounting for less than 10%.[3]

Presentation of MZL varies widely depending on the subtype, as well as where the primary tumour is located. Gastric MALT occurs in the stomach and is often associated with chronic infection of H. pylori. Another pathogen linked to EMZL of the eye is C. psittaci, though support for this association varies across geographic regions. MZL has been associated with hepatitis C infection but with a similarly ambiguous association. Further, unlike MALT associated with H. pylori, response to antibiotics is more variable, according to Jeffrey A. Bubis, DO, FACOI, FACP.

Current treatment protocol

Treatment depends on the disease type, stage, and reason for treatment, according to Dr. Bubis. He provides an example of a patient presenting with MALT with H. pylori, noting that treatment for H. pylori can be adequate therapy, with some studies suggesting this leads to long-term, disease-free survival.

Overall, the medical community’s understanding of MZL’s pathophysiology is rapidly evolving, making targeted treatment more possible. First-line treatment of localised MZL is often targeted with treatment of the associated pathogen (with H. pylori showing the strongest response, while data for other pathogens is weak), along with targeted radiation and, in the case of SMZL, splenectomy, according to the authors of an article in Current Oncology.[5]

Chemo-immunotherapy is considered the first line of treatment for most symptomatic, advanced MZL. Other treatment avenues include single-agent rituximab, which is used alone or in combination with chemotherapy.

Use of BTKis

Bruton’s tyrosine kinase inhibitors (BTKis) work by impairing cell proliferation, migration, and activation of NF-κB.[6] Ibrutinib was the first BTKi to be approved for treatment, with an overall response rate in relapsed or refractory MZL of 48%, per the Blood Advances study. However, as noted, toxicity is a concern, given risks including atrial fibrillation/flutter and bleeding risk. 

Per the Blood Advances study, zanubrutinib was better tolerated with similar efficacy results to previously available treatments in MZL patients, and it is FDA-approved for this indication. 

As zanubrutinib is better tolerated, the study authors hope this will lead to less discontinuation of treatment and therefore better long-term effects. It is now being studied as a combination therapy with other treatment options.

Disclaimer: This story is contributed by Courtney Manser and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.