Backgroud: Synergistic antitumor effect with combination of fludarabine and rituximab has been demostrated on MALT cells. Addition of rituximab to other drugs has improved outcomes in several types of NHL without a significant addition of toxicity. Our aim was to evaluate the safety and efficacy of rituximab combined with fludarabine (RF) in first-line therapy for extranodal MALT lymphoma.

Patients and methods: Adult patients with untreated extranodal MALT lymphoma who were included and received rituximab 375 mg/m intravenously (IV) on day 1 and fludarabine 25 mg/m (IV) given on days 1–5 (days 1–3 in > 60 years), every 4 weeks; after the first cycle, oral fludarabine was permitted. After 3 cycles, a work-up was done. Patients in complete remission (CR) received an additional cycle and, if partial remission (PR), a total of 6 cycles.

Results: 22 patients were included. Characteristics: median age: 60 years (32–83); 45% male; PS 0–1 (100%); site of lymphoma origin: gastric (61%) and extragastric (39%); stage: I (45%), II1 (23%), II2 (5%) and IV (27%). A total of 101 cycles of RF were administered and 21 pts were evaluable for response. After the third cycle, 13 pts (62%) achieved CR and 8 pts (38%) PR. At the end of therapy, 19 pts (90%) achieved CR and 2 pts (10%) PR. Univariate analysis identified primary extragastric disease as an adverse factor to reach CR after 3 cycles of RF (HR 23.3 (95% CI, 2.0–273.3)). The median follow-up time was 23 months (95% CI, 18–27 months). Progression free survival (PFS) at 24 months was 88 % (95% CI, 80–100%). PFS at 24 months in gastric and extragastric MALT lymphoma were 100% and 79%, respectively. Tolerance to oral fludarabine was excellent. Mild neutropenia was the most common toxicity, usually presenting after the third cycle and 2 pts had prolonged mild thrombocytopenia. No grade 3–4 infections were observed.

Conclusions: Immunochemotherapy with RF, either with intravenous or oral fludarabine, achieves a high CR rate in both gastric and extragastric MALT lymphoma, although the firsts responded faster. With only four cycles of RF, two thirds of patients achieves CR. RF is associated with a good safety profile being mild granulocytopenia and thrombocytopenia the main adverse events. The long-term benefit of this therapy will require prolonged follow-up.

Disclosures: Off Label Use: Due to the limited number of patients with MALT lymphoma, there is no standard treatment for this type of lymphoma. Rituximab and fludarabine is a common tretament used in several lymphomas. We started a pilot study (in compasionate use) to explore tis combination, following local policies of Ethical Committes..

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