A Multicenter Prospective Study of First-Line Antibiotic Therapy for Early-Stage Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma and Diffuse Large B-Cell Lymphoma with Histological Evidence of MALT

Background: To evaluate the efficacy of first-line Helicobacter pylori (HP) eradication (HPE) therapy against HP-positive gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphomas (DLBCL) with histological evidence of MALT (DLBCL[MALT]). Methods: Patients with gastric DLBCL(MALT) (n=10) and gastric MALT lymphoma (n=36) who had participated in a multicenter prospective study on first-line HPE therapy, conducted by the Taiwan Cooperative Oncology Group between December-2006 and September-2014, were enrolled. The HPE regimen consisted of omeprazole, amoxicillin, and clarithromycin for 14 days. The histological responses of tumors were re-assessed using the Groupe d'Etude des Lymphomes de l'Adult (GELA) scoring system. The primary end point was the therapeutic efficacy (complete remission, CR) of first-line HPE. The levels of expression of cytotoxin-associated gene A (CagA), BCL10, and NF-κB and the presence of t(11;18)(q21;q21) associated with HP-independence (lack of lymphoma regression after HPE) were assessed. Findings: Of the total 46 patients, 34 (73.9 %) achieved CR, including eight with DLBCL(MALT) and 26 with MALT lymphoma. The CR rates for patients with stages IE (n=40) and IIE1 (n=6) tumors were 75.0 % and 66.7 %, respectively. The frequency of CagA expression was significantly higher (85.3 % [29/34] vs 33.3 % [4/12]; p=0.001), whereas the frequency of nuclear BCL10 expression was significantly lower (8.8 % [3/34] vs 83.3 % [10/12]; p<0.0001), in HP-dependent tumors than in HP-independent tumors. The expression of nuclear NF-kB was significantly associated with HP-independence (p=0.0001). The API2-MALT1 fusion transcript was detected in 4 (33.0 %) of the 12 HP-independent MALT lymphomas, but in none of the 10 DLBCL(MALT) tumors. Interpretation: HPE is considered a first-line treatment for early-stage HP-positive DLBCL(MALT) as well as MALT lymphoma of the stomach. BCL10, and/or NF-kB are potential therapeutic targets in these lymphoma subtypes. Trial Registration Number: This trial is registered with ClinicalTrials.gov, number NCT00327132. Funding Statement: This study was sponsored, conducted and analyzed by the TCOG and following research grants: MOST 107-2314-B-002 -217-MY3 from Ministry of Science and Technology, Taiwan, and MOHW107-TDU-B-211-123002 from Ministry of Health and Welfare, Taiwan. Declaration of Interests: All authors declare they have no competing interests. Ethics Approval Statement: All experimental protocols were approved by the Institutional Review Board (IRB) of the Research Ethical Committee of National Taiwan University Hospital (NTUH) (NTUH IRB numbers: 950606).