What is the optimal management of mucosa-associated lymphoid tissue (MALT) lymphoma?

Optimal Management of Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

The optimal first-line management of gastric MALT lymphoma is antibiotic therapy for Helicobacter pylori eradication, which can induce lymphoma regression and long-term clinical disease control in most patients. 1

Treatment Algorithm Based on H. pylori Status

H. pylori-Positive Gastric MALT Lymphoma (Stage IE-IIE)

• Eradication of H. pylori with antibiotics should be the sole initial therapy for localized H. pylori-positive gastric MALT lymphoma [Level II, A] 1
• Standard regimen includes proton-pump inhibitor (PPI) plus clarithromycin-based triple therapy with either amoxicillin or metronidazole for 10-14 days 1
• H. pylori eradication should be confirmed by urea breath test or stool antigen test at least 6 weeks after therapy and 2 weeks after PPI withdrawal 1
• If initial eradication fails, second-line therapy with alternative triple- or quadruple-therapy regimens should be attempted 1
• Wait at least 12 months before starting another treatment in patients who achieve clinical and endoscopic remission with H. pylori eradication, even if persistent lymphoma is present at histological level 1
• Lymphoma regression can take from a few months to >12 months after successful H. pylori eradication 1

H. pylori-Negative Gastric MALT Lymphoma or Non-Responsive to Antibiotics

• A trial of anti-Helicobacter regimen may still be worthwhile in H. pylori-negative cases, as occasional responses have been reported (possibly due to false-negative tests or infection by other Helicobacter species) 1
• If no signs of lymphoma regression are seen at repeat endoscopy 2-3 months after antibiotics, oncological treatment should be considered 1
• For localized disease (stage IE-IIE), moderate-dose involved-field radiotherapy (24-30 Gy to stomach and perigastric nodes given in 3-4 weeks) is the preferred option [Level III, B] 1
• For systemic disease (stage IV), rituximab plus chemotherapy is appropriate for symptomatic patients [Level III, A] 1

Special Considerations

Monitoring After Treatment

• Endoscopic follow-up with multiple biopsies is essential, performed 2-3 months after treatment to document H. pylori eradication 1
• Subsequently, endoscopy with biopsies should be performed at least twice per year for 2 years to monitor histological regression 1
• In case of persistent but stable residual disease, a watch-and-wait policy may be safe [Level IV, C] 1, 2

Treatment Options for Refractory or Advanced Disease

• Chemotherapy options include oral alkylating agents (cyclophosphamide or chlorambucil) or purine nucleoside analogues (fludarabine, cladribine) 1
• Rituximab has shown activity in phase II studies, and its combination with chlorambucil has proven efficacy in a randomized study [Level II, A] 1
• Surgery (total gastrectomy) has not been shown to achieve superior results compared to more conservative approaches and may impair quality of life - it no longer has a role in initial treatment 1

Important Caveats

• Molecular follow-up studies have shown persistence of monoclonal B-cells in >50% of cases in histological remission after antibiotic therapy, but the clinical significance remains unclear 3, 4
• Patients with t(11;18) translocation are less likely to respond to antibiotics alone and will most probably be unresponsive to alkylating agents as sole treatment 1
• Aggressive anthracycline-containing regimens should be reserved for patients with very aggressive clinical course or histological transformation 1
• Long-term follow-up is mandatory for all patients who received antibiotic treatment due to possibility of late relapses 3

Based on the evidence presented, antibiotics for H. pylori eradication represent the optimal first-line management of gastric MALT lymphoma, with other therapies (radiotherapy, chemotherapy, immunotherapy) reserved for non-responsive cases or advanced disease.