Rituximab Maintenenance Therapy Prolongs Event Free Survival in Patients with CD20+ B-Cell Non-Hodgkin-Lymphoma.

Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients with CD20+ B-cell Non-Hodgkins-Lymphoma. After completion of standard treatment patients were randomized to either observation or maintenance therapy with rituximab (375 mg/m²) every 3 months for 2 years. Patients after first line therapy as well as relapse patients were included in the study. Patients with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Patients with aggressive lymphoma with residual tumor mass were examined with positrone emission tomography (PET) and qualified for randomization if PET showed no signs of tumor activity. Patients with indolent lymphoma qualified for the study if at least a partial response (PR) was achieved. After recruitment of 172 patients a planed interim analysis was performed. Complete data sets of 162 patients (pts) with CD20+ B-cell Non-Hodgkins-Lymphoma were evaluable for analysis. Histological subtypes included diffuse large cell lymphoma (69 pts), follicular lymphoma (41 pts), mantle cell lymphoma (18 pts), primary mediastinal lymphoma (15 pts), marginal zone lymphoma (9 pts), Burkitt’s lymphoma (3 pts), immunocytoma (2 pts), primary intestinal lymphoma (1 pt), hairy cell leukemia (1 pt), chronic lymphocytic leukemia (1 pt) and unclassified B-cell lymphoma (2 pts). The interim analysis showed that event free survival was significantly prolonged in the rituximab maintenance group compared to the observation group (p<0.05). However, no difference in overall survival between the two groups was observed so far. Two patients in the treatment group developed WHO grade III adverse events (1 leucopenia, 1 infection). Both pts recovered shortly after appropriate treatment. We conclude that rituximab maintenance therapy is feasable, safe and well tolerated in patients with CD20+ B-cell Non-Hodgkins-Lymphoma and may prolong event free survival in this patient population.