Treatment of Low-Grade Non-Hodgkin Lymphomas with Fludarabine and Mitoxantrone Followed by Rituximab Maintenance: Results of a Phase II Study.

The combination of fludarabine and mitoxantrone (FN) has been a well-tolerated and effective regimen for the treatment of indolent lymphomas. Rituximab is an active agent for the treatment of CD20-positive B-cell lymphomas. In the present study, we sought to determine the activity of FN chemotherapy followed by maintenance Rituximab in indolent lymphomas. Patients with indolent lymphoma received fludarabine 25 mg/m² day 1–3 and mitoxantrone 10mg/m² every 28 days. Patients who attained a response (CR or PR) received 4 weekly doses of Mabthera 375mg/m² 1 month and 3 months after completion of treatment. The primary endpoint of the study was to evaluate the response to this regimen and secondary endpoints were survival and toxicity. Forty-six patients were included in the study. The median follow-up time was 29 months. Six patients were stage I, 8 stage II, 3 stage III and 29 stage IV. Histology was distributed as follows: small lymphocytic lymphoma (SLL) 15 patients, splenic marginal zone lymphoma 3, lymphoplasmocytic lymphoma 1, marginal zone B-cell lymphoma 16 (extranodal 12 and nodal 4), follicular grade I 6 and follicular grade II 5 patients. The median number of delivered cycles was 6. Fifty-two percent of patients attained a complete response (CR) and 39% a partial response (PR) for an overall response rate of 91%. One patient had stable disease, one had progression of the disease, whereas 2 were non-evaluable. After a median follow-up of 29 months, 34 of 46 patients (74%) are alive and disease-free. Grade III and IV toxicities included neutropenia (28%), thrombocytopenia (7%), anemia (4%), and diarrhea (2%). In conclusion, FN followed by Rituximab maintenance is an active and well-tolerated regimen in the treatment of patients with indolent lymphomas.