Rituximab (Rituxan) has shown high activity in relapsed follicular lymphomas when given alone, and phase II studies indicate that its addition to chemotherapy may further improve response rates substantially. Because prospective randomized studies have not been available so far, the German Low Grade Study Group (GLSG) started a multicenter national trial in patients with relapsed or refractory follicular cell lymphoma (FCL) or mantle cell lymphoma (MCL). As patients were treated for first-line therapy with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin(Drug information on doxorubicin) HCl, vincristine [Oncovin], prednisone), the FCM (fludarabine [Fludara], cyclophosphamide(Drug information on cyclophosphamide), mitoxantrone(Drug information on mitoxantrone) [Novantrone]) combination was chosen for salvage chemotherapy.
The FCM combination included fludarabine at 25 mg/m2 days 1-3, cyclophosphamide at 200 mg/m2 days 1-3, and mitoxantrone at 8 mg/m² day 1. This treatment was repeated for four cycles every 28 days. Patients were prospectively randomized to FCM alone or FCM plus rituximab(Drug information on rituximab) at 375 mg/m² on the day before FCM therapy. Since November 1998, 147 cases were randomized, 80 of whom are currently evaluable for response. A total of 43 patients had FCL, and 27 patients were diagnosed with MCL, and 10 patients presented with lymphocytic lymphoma. Statistically, both treatment arms were monitored by sequential testing, which indicated a significant difference between both treatment arms as of June 2001.
In patients treated with FCM alone 53% complete and partial remissions were observed (15% CR, 38% PR), whereas in the group receiving FCM plus rituximab an overall response rate of 89% was obtained (36% CR, 53% PR) (P = .000715). Similar improvements in remission rates were detected in FCL (95% vs 68%) as well as in MCL (77% vs 27%). Both treatment options were associated with hematologic toxicities of grades 2 to 4, but were well tolerated. Only one treatment-related death was observed in the rituximab plus FCM arm, and three in the FCM arm.
CONCLUSION: This study is, to our knowledge, the first prospective randomized trial investigating the addition of rituximab to combination chemotherapy in FCL and MCL. It demonstrates a significant improvement of the combined strategy in patients with relapsed or refractory disease.