Rituximab Combined with Intravenous or Oral Fludarabine for Previously Untreated Mucosa Associated Lymphoid Tissue (MALT) Lymphoma Patients.

Background: Fludarabine as a single agent or in combination with chemotherapy has shown activity in MALT lymphoma. Our ex vivo preliminary results indicate a synergistic antitumor effect on MALT cells with combination of fludarabine and rituximab. The addition of rituximab to other drugs has improved outcomes in several types of NHL without a significant addition of toxicity.

Methods: This study enrolled adult patients with untreated MALT lymphoma who were candidate to receive systemic treatment. Patients received rituximab 375 mg/m² intravenously (IV) on day 1 and fludarabine 25 mg/m² (IV) given on days 1–5 (days 1–3 in > 60 years), every 4 weeks; after the first cycle, oral fludarabine was allowed to be given orally at 40 mg/m² with the same schedule. After three cycles, a work-up was done. Patients in CR received an additional cycle and, if PR, a total of 6 cycles was recommended. Use of G-CSF and prophylactic antibiotics was optional.

Results: Characteristics of all 18 pts: median age: 59 years (range: 32–83); 7 male, 11 female; PS 0 (94%); site of lymphoma origin: stomach (61%), skin (16%), lung (11%), parotid gland (11%); stage: I (66%), II (16%) and IV (16%). A total of 82 cycles of R-F were administered; 2 pts received 2 cycles, 9 pts 4 cycles, 7 pts 6 cycles. 17 pts are evaluable for response. Overall response rate was 100% with 94% achieving CR. In the pt in PR, symptoms resolved and received no further treatment. One pt with parotid gland involvement at dx relapsed at 6 m from the end of treatment in two unaffected areas at dx (breast and bone marrow). Median follow-up from starting treatment is 15 m (range: 17–27). PFS rate is 93% (CI95%: 79–100%) at 12 m and OS rate is 100% at 12 m. Tolerance to oral fludarabine was excellent with many patients preferring this formulation. Mild neutropenia was the most common toxicity, usually presenting after the third cycle. 1 pt developed a prolonged grade 4 neutropenia after the 6^th cycle. No blood transfusions were required. 3 pts developed grade 2 respiratory infection, but none pt had to be admitted.

Conclusions: These preliminary data indicate that the RF regimen, either with intravenous or oral fludarabine, was well tolerated even in elderly patients. This combination is very active for the treatment of untreated MALT lymphoma, even with fewer cycles than initially planned. A phase II national multicenter study is being planned.