Fludarabine, Aracytine and Rituximab Based Chemotherapy In Patients with Refractory and Relapsed Mantle Cell Non-Hodgkin Lymphoma

Mantle cell lymphoma (MCL) is a distinct B cell non Hodgkin lymphoma characterized by CD 5 expression, t (11; 14)(q13; q32) translocation and over-expression of Cyclin D1, and frequently has an aggressive clinical course. There is no standard of care for the treatment of MCL. Current treatment approaches are non curative and pts median survival is 4–6 years. Various studies have reported promising results for a high dose Cytarabine-containing regimen in the treatment of MCL. Fludarabine has also been recognized as effective treatment in pts with MCL, either as a single agent or in combination with other drugs. The addition of Rituximab improves the response to the treatment. The aim of this study is to assess the efficacy and toxicity of a combination of Fludarabine, Aracytine and Rituximab treatment in refractory and relapsed MCL.

We retrospectively evaluated 20 pts with refractory or relapsed MCL treated in our institution between February 2007 and February 2010.

Median age was 59 yrs (54-77 yrs), 14 pts (70%) were males, 18 pts (90 %) had stage IV, 16 pts (80%) had bone marrow involvement, 16 (80%) presented comorbidities. Eight pts (40%) were in first relapse, 12 (60%) in second relapse. Twelve pts (60%) had a “Mantle Cell Lymphoma International Prognostic Index” (MIPI) score ≥ 7. Therapy included: fludarabine 25 mg/m²/daily intravenously for 3 days, aracytine 500 mg/m²/daily for 3 days and Rituximab 375 mg/m²/daily for 1 day, Dexamethasone 8 mg daily for 3 days, every 28 days for 4 cycles.

Eight pts (40%) achieved complete response (CR) and 4 pts (20%) a Partial Remission (PR) with an overall response rate (ORR) of 60%. Eight pts (40%) progressed and one of them died of active disease. After a median follow up of 17 months (range 8–36), OS is 70% and PFS is 55%.

Toxicity was mainly hematological with grade >=3 neutropenia in 40 (50%) of the 80 cycles performed, grade >=2 anemia in 30 (37%) and grade 4 thrombocytopenia in 24 (30%). In 16 (20%) cycles pts required red blood cells transfusions, in 12 (15%) platelet transfusions. One episode of Herpes Zoster infection was observed.

This study suggests that the combination of Fludarabine, Aracytine and Rituximab appears to be an effective regimen with a promising response rate and manageable toxicity, for pretreated pts often affected by comorbidities and with poor prognosis.

Further studies are needed to assess the efficacy of this combination therapy and to further test the role of this approach in MCL.

No relevant conflicts of interest to declare.