Antibiotics as first-line therapy for Hp-associated gastric large B-cell lymphoma? Probably yes.

Two decades after the first cure of Helicobacter pylori (Hp)–associated marginal zone B-cell lymphoma of the stomach by eradicating the bacterium,¹  it is still amazing to witness the success of this treatment in a high proportion of patients.

How it works is still unclear. The most logical hypothesis, that the lymphoma is driven through tonic B-cell receptor triggering by some Hp antigen, has not been proven. Alternatively, T-cell dependency of this slowly growing lymphoma has been suggested. Antibiotics may decrease the bacteria- sustained mucosal T-cell response, thereby preventing the cytokine production needed to sustatin the lymphoma.²  But how does this explain lymphoma regression in perigastric lymph nodes that are normally crammed with T cells? And what accounts for the efficacy of antibiotics in the absence of Hp?³ 

This lack of mechanistic explanation has not kept hemato-oncologists from trying to see whether or not Hp eradication had a beneficial effect on aggressive, large-cell gastric B-cell lymphomas. And, yes, it had. Both large-cell lymphoma evolving into gastric marginal zone B-cell lymphoma and “de novo” large-cell gastric B-cell lymphoma have regressed on antibiotic treatment, as cited in this issue of Blood in Kuo et al.⁴ 

Kuo and colleagues report a series of patients diagnosed with stage IE and stage IIE Hp-positive gastric diffuse large B-cell lymphoma (DLBCL) with and without a coexisting marginal-zone B-cell component of mucosa-associated lymphoid tissue (MALT) type treated with antibiotic Hp eradication therapy. The reported cure rates are amazing: 18 of 32 combined marginal-zone and DLBCLs and 11 of 16 pure DLBCLs were cured, with time to remission ranging between 0.6 and 7.5 months. Except for 1 patient who relapsed in the lung, all others stayed free from disease during a mean follow-up of 7.7 years. Those patients who failed to respond to antibiotics as verified by frequent follow-up by gastroscopies with biopsies were treated with standard chemotherapy. Given the excellent results of combined standard therapy in gastric DLBCL,⁵  the risk taken by delaying standard treatment onset is fairly low. And the benefit in case of antibiotic efficacy is substantial, given the toxicity of chemotherapy in this largely elderly population.

The fact that more than half of the patients with gastric large B-cell lymphoma were cured by antibiotics underscores its peculiarity within the comprehensive group of DLBCL. This observation fits the growing cytogenetic and expression signature evidence that most (but not all) gastric large-cell lymphomas are transformed marginal-zone B-cell lymphomas.^6-8 

The cure rate of gastric large B-cell lymphoma with antibiotics might be even higher if this large-cell marginal-zone lymphoma could be reliably diagnosed as such. At present, this is difficult because hematopathologists have not yet agreed on a specific immunophenotype for it and sorting out the DLBCL subtypes as defined by the World Health Organization classification would presently require comprehensive gene probe analysis. Even so, the series reported by Kuo et al is a solid base for initiating a multicenter trial testing antibiotics as first-line therapy (followed by rescue chemotherapy in case of unresponsiveness) against current standard protocols (combination of an anthracycline-based chemotherapy and rituximab with or without consolidation radiotherapy⁵ ), for example, adverse effects and quality of life.