Rituximab for Treatment of Advanced Extranodal Marginal Zone B Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue Lymphoma

Abstract

Background: Extranodal marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) is a relatively common type of lymphoma. Owing to its B cell lineage, it appears to be a potential target for treatment with the CD20 antibody rituximab. We present an analysis of our experience with rituximab for treatment of patients with advanced MALT lymphoma. Patients and Methods: A retrospective analysis of patients with histologically verified MALT lymphoma undergoing treatment with rituximab was done. After reassessment of histological samples for the presence of MALT lymphoma, patients were evaluated as regards date of diagnosis, prior therapy for MALT lymphoma, sites of involvement upon treatment with rituximab, clinical response in terms of complete remission (CR), partial response (PR), stable disease (SD) and progressive disease as well as symptomatic response, duration of response and survival. Results: A total of 9 patients with advanced MALT lymphoma undergoing therapy with single-agent rituximab were identified. All patients received treatment at a dose of 375 mg/m² once weekly ×4. One patient each had relapsed after chemotherapy and radiation, respectively, while none of the other 7 patients had received prior cytotoxic treatment or radiation. Three patients achieved a CR, 2 patients had PR for 6 and 14 months, while the remaining patients had SD between 8 and 18+ months. One patient died of progressive disease in spite of the initiation of chemotherapy and 1 patient succumbed to a cardiovascular event while having been in ongoing PR for 11 months. The other 7 patients are currently alive with disease 10–27 months after initiation of therapy. Follow-up biopsies for histological assessment were available in 5 patients with gastric lymphoma. In 1 patient with SD, however, persistence of CD20-positive cells within lymphoepithelial lesions was noted in spite of almost complete depletion of B lymphocytes from the normal gastric mucosa, suggesting either recirculation of MALT lymphoma cells to these lesions or defining lymphoepithelial lesions as a sanctuary site from rituximab penetration. Conclusion: Rituximab had only moderate activity in terms of inducing objective responses in our unselected and heterogeneous cohort of patients with disseminated MALT lymphoma. Long-term disease stabilization, however, along with a symptomatic benefit was seen in all patients. Our data nevertheless indicate that rituximab might not optimally penetrate into the gastric mucosa in all patients.

Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie

“…2,3 Efficacy data for both rituximab and cladribine are available for B-cell neoplasms and some limited data have also been reported for MALT lymphoma. [5][6][7] Cladribine is a potent purine nucleoside analogue with cytotoxic effects on both dividing and non-dividing lymphocytes. It is remarkably effective in hairy cell leukemia, with overall response rates of up to 98%, and is currently considered standard therapy in this disease.…”

“…While the role of the chimeric anti-CD20 antibody rituximab in combination with chemotherapies is undisputed in almost all types of B-cell lymphomas, its use in MALT lymphoma is being tested in an ongoing randomized trial and it is currently not approved for this indication in Europe. Although it has been shown to have good palliative potential in patients with MALT lymphoma, 7 various caveats such as suboptimal penetration of the antibody into the gastric mucosa 7 and induction of plasmacytic differentiation 11 have been raised. The latter might lead to resistance of the disease to rituximab-containing therapies, as plasma cells are devoid of CD20 expression.…”

“…4 Both the anti-CD20 antibody rituximab and the nucleoside analogue 2-chlorodeoxyadenosine (cladribine, 2CdA) are effective drugs in the treatment of B-cell lymphomas and have been tested in patients with MALT lymphomas. [5][6][7] Although both agents have a favorable toxicity profile, some caveats concerning their use remain, such as suboptimal penetration of rituximab into mucosal structures and the inferior response of non-gastric MALT lymphomas as opposed to gastric disease when using cladribine. As MALT lymphomas show a very indolent clinical course with good response rates to various therapeutic agents, the objective in systemic therapy of MALT Currently, there is no standard systemic treatment for extranodal marginal zone B-cell lymphoma of the mucosaassociated lymphoid tissue.…”

Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue

“…Raderer and colleagues retrospectively evaluated response to rituximab in nine patients. Three achieved a CR and two achieved a PR for 6 and 14 months [94]. A phase II study of 35 patients by the International Extranodal Lymphoma Study Group documented a 73% response rate, with a median time to best response of 2.2 months.…”

Practice guidelines for the management of extranodal non-Hodgkin's lymphomas of adult non-immunodeficient patients. Part I: primary lung and mediastinal lymphomas. A project of the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation

“…[31][32][33] Due to the absence of comparative studies, the panel provided recommendations based mostly on consensus formation techniques and according to a good clinical practice principle (grade D).…”