Final Results of a Multicenter Phase II Trial Assessing the Activity and Efficacy of Helicobacter Pylori-Eradicating Antibiotic Therapy As Exclusive Treatment for Patients with Stage I-II1 Diffuse Large B-Cell Lymphoma of the Stomach (the HGL-1 Trial)

Helicobacter pylori (Hp) infection is associated with the pathogenesis of marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)-type of the stomach, and Hp-eradicating antibiotic therapy is the standard treatment for this lymphoma, with complete remission rates of 60–80%. Hp is also detected in 35% of diffuse large B-cell lymphomas (DLBCL) of the stomach, being more common in cases with concomitant MALT areas with respect to de novo cases (65% vs. 15%). However, the role of Hp-eradicating antibiotic therapy in gastric DLBCL remains to be elucidated, since only rare and small, monoinstitutional retrospective studies are available. Herein, we report the final results of a multicentre phase II trial, the first one in Western countries, addressing the role of Hp-eradicating therapy as exclusive treatment in patients with gastric DLBCL.

To assess feasibility, activity and efficacy of Hp-eradicating therapy as exclusive treatment for limited-stage DLBCL of the stomach.

Inclusion criteria were histopathologic diagnosis of DLBCL, with or without concomitant MALT-type areas; Hp-infection assessed by multiple gastric biopsies and/or breath test; stage I-II1 of disease according to Musshoff staging system; perigastric lymph nodes diameter <1.5 cm; normal lactate dehydrogenase (LDH) serum level; age ≥18 years old; ECOG-Performance Status <3; absence of HIV-infection or history of previous cancer; absence of bleeding lesions (hemoglobin >9 g/dl). Registered patients received clarithromycin 500 mg bid, tinidazole 500 mg bid and omeprazole 20 mg bid, orally, for 7 consecutive days. Objective response and bacterial eradication were assessed at 30 and 60 days from antibiotics by gastric endoscopy-ultrasonography, biopsies and breath test. Patients who did not achieve Hp eradication received a second-line antibiotic therapy according to local guidelines. Eradicated patients who achieved complete lymphoma remission (CR) were referred to follow-up; patients with partial response (PR) received rituximab as complementary therapy; patients with stable (SD) or progressive (PD) disease received conventional treatment (R-CHOP ± radiotherapy).

From 2003 to 2010, 16 patients (median age 70; range 38–87; 11 males) were enrolled. Eleven patients had de novo DLBCL, while 5 patients presented concomitant MALT areas. Ten patients had stage II1 disease, 5 had stage IE. Five patients presented anemia; two patients had concomitant HCV infection. None presented systemic symptoms.

Eradicating therapy was completed in all patients with excellent tolerability. Eradication was documented at one month in 15 patients and after second-line antibiotic-therapy in the remainder patient. Lymphoma regression was complete in 8 (50%) patients and partial in 3 (ORR= 69%; 95% CI= 47%–91%). Two of the three PRs achieved CR after rituximab, with a CRR after experimental therapy of 63% (95% CI= 39%–87%). Objective response was not associated with stage or concomitant MALT areas.

At a median follow-up of 53 months, 9 of the 10 patients who achieved CR after experimental therapy remain relapse-free, the remainder experienced relapse at 10 months, with a median DFS of 68+ months. Treatment failure was observed in 7 patients: 5 patients with SD/PD after antibiotics, one patient in PR who did not receive rituximab and the single patient with relapsing disease; they were referred to conventional chemoradiation treatment, achieving CR in all cases, and none of them experienced relapse after 13–128 months (median 41+).

No patient died of lymphoma; two patients died of cardiac failure and gallbladder cancer, respectively; the remaining 14 patients are alive (13 disease-free), with a 5-yr OS of 94%.

Patients with stage I-II1 Hp-associated DLBCL of the stomach can be safely managed with antibiotics alone. Half of treated patients will achieve long-term remission without chemotherapy, a critical issue considering that two-thirds of patients are >65 years old. Importantly, unresponsive patients can be safely salvaged with conventional treatment. Registered cases of Hp-associated DLBCL of the stomach will be characterized under pathologic and molecular perspectives to identify parameters useful to distinguish the best candidates for eradicating therapy.

No relevant conflicts of interest to declare.