Rituximab-CHOP Significantly Improve the Response of Advanced Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT Lymphoma).
Authors: Ennishi Daisuke , Terui Yasuhito , Myojo Tomohiro , Mishima Yuko , Yokoyama Masahiro , Takahashi Shunji , Takeuchi Kengo , Hatake Kiyohiko 
Published: April 2020

Abstract
Introduction: MALT lymphoma, even if advanced stage, is known to have indolent outcome. However, previous reports showed that chemotherapy only could not improve the disease progression. Recently a few reports demonstrated rituximab monotherapy could not acquired enough response for the patients with advanced MALT lymphoma. We retrospectively analyzed outcomes of patients with advanced MALT lymphoma treated with rituximab monotherapy or rituximab-CHOP like regimen (R-CHOP), and discussed about the treatment of this entity. We also performed the immunohistochemcal study of bcl-2 and reverse-transcription polymerase-chain-reaction (RT-PCR) analysis of API2-MALT1, and evaluate whether the existence of bcl-2 or API2-MALT1 makes any influence on the response to rituximab treatments.
Patients and methods: Between October 2001 and October 2005, 106 patients (pts) were treated in our institute and 21 pts with advance-staged MALT lymphomas were included in this study. Advanced stage with GI tract MALT lymphoma was defined as a stage II1+2 or IV according to Lugano staging system. On the other hand, advanced stage with non-GI tract lymphoma was defined as a stage III or IV. In this study, immunohistochemical staining with bcl-2 and RT-PCR analysis of API2-MALT1 were performed.
Results: Twenty-one pts (12 men and 9 women) were treated with rituximab treatment and a median age was 65 years (27–83 years). Stage II+III pts and IV pts were 9 pts (22.9%) and 12 pts (57.1%), respectively. Three of five HP-positive pts did not respond antibiotic therapy. The remaining HP-negative 16 pts received rituximab therapy as first line treatment. Of the patients who required systemic chemotherapy, 16 pts were treated with R-CHOP; 5 pts with rituximab monotherapy. The overall response rates (ORR) were 100% (CR rate = 62.5%) in the R-CHOP group, 60% (CR rate = 60%) in rituximab monotherapy, respectively. The median follow up was 2.2 years. Relapse rate were 6.2% (1/17) in the R-CHOP group, 40% (2/5) in the rituximab monotherapy, respectively. Bcl-2 was expressed in 11 of 17 tissues tested, and CR rates were 63.3/37% in bcl-2 +/− patients. Grade 3 to 4 cytopenia was observed in 87.5% of patients in R-CHOP group, but not in rituximab monotherapy. Grade3 to 4 non-hematological toxicity was not seen in both groups.
Conclusion: R-CHOP exhibited impressive efficacy with one failure among 17 patients. ORR was also significantly better in R-CHOP group than in rituximab monotherapy. The efficacy of rituximab monotherapy was similar to previous reports. These results strongly suggest that R-CHOP improves the response of advance-staged MALT lymphoma. In this study, bcl-2 and API2-MALT1 did not contribute to response to rituximab treatment. R-CHOP is expected to prolong relapse-free survival compared to rituximab monotherapy or chemotherapy only. Scince hematologic toxicity in R-CHOP group is severe, R-CVP regimen which is less toxicity may be necessary to be evaluated.