The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.

In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab may improve the prognosis when combined with chemotherapy. This was investigated in a prospective randomized study in patients with relapsed disease. A total of 147 patients were randomized to receive 4 courses of chemotherapy with 25 mg/m(2) fludarabine on days 1 to 3, 200 mg/m(2) cyclophosphamide on days 1 to 3, and 8 mg/m(2) mitoxantrone on day 1 (FCM), alone or combined with rituximab (375 mg/m(2); R-FCM). Of 128 evaluable patients, 62 were randomized for FCM and 66 for R-FCM. R-FCM revealed an overall response rate of 79% (33% complete remission [CR], 45% partial remission [PR]) as compared with 58% for FCM alone (13% CR, 45% PR; P = .01), with similar results in a subgroup analysis of FL (94% vs 70%) and MCL (58% vs 46%). In the total group, the R-FCM arm was significantly superior concerning progression-free survival (PFS; P = .0381) and overall survival (OS; P = .0030). In FL PFS was significantly longer in the R-FCM arm (P = .0139) whereas in MCL a significantly longer OS was observed (P = .0042). There were no differences in clinically relevant side effects in both study arms. Hence, the addition of rituximab to FCM chemotherapy significantly improves the outcome of relapsed or refractory FL and MCL.