Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide.

PURPOSE: Alkylating agents and the anti-CD20 monoclonal antibody rituximab are among appropriate choices for the primary treatment of symptomatic patients with Waldenström macroglobulinemia (WM), and they induce at least a partial response in 30% to 50% of patients. To improve these results, we designed a phase II study that included previously untreated symptomatic patients with WM who received a combination of dexamethasone, rituximab, and cyclophosphamide (DRC). PATIENTS AND METHODS: Seventy-two patients were treated with dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5 (total dose, 1,000 mg/m2). This regimen was repeated every 21 days for 6 months. Patients' median age was 69 years and many had features of advanced disease such as anemia (57%), hypoalbuminemia (40%), and elevated serum beta2-microglobulin (43%). RESULTS: On an intent-to-treat basis, 83% of patients (95% CI, 73% to 91%) achieved a response, including 7% complete, 67% partial, and 9% minor responses. The median time to response was 4.1 months. The 2-year progression-free survival rate for all patients was 67%; for patients who responded to DRC, it was 80%. The 2-year disease-specific survival rate was 90%. Treatment with DRC was well tolerated, with 9% of patients experiencing grade 3 or 4 neutropenia and approximately 20% of patients experiencing some form of toxicity related to rituximab. CONCLUSION: Our large, multicenter trial showed that the non-stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.

Extended rituximab therapy for previously untreated patients with Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia is a low-grade lymphoplasmacytoid lymphoma characterized by CD20 expression on malignant cells. Several studies have indicated that the anti-CD20 monoclonal antibody rituximab has activity against this disease. Thus, we performed a prospective study in which 17 previously untreated patients with symptomatic macroglobulinemia were treated with rituximab 375 mg/m2 intravenously for 4 weeks. Three months after completion of rituximab, patients without evidence of progressive disease received repeat 4-week courses of this agent. Six patients (35%) achieved a partial response after extended treatment with rituximab. Median time to response was 3 months. The median time to progression (TTP) for all patients was 13 months. One of 6 responding patients has progressed at 10 months, while the other 5 patients remain progression free with a follow-up range of > 22-40 months. Eight patients (47%) were rated as stable disease, and their median TTP was 9 months. Treatment with rituximab was well tolerated and was not associated with myelosuppression; one third of the patients experienced infusion-related toxicity, usually fever and chills of mild degree. Our prospective trial of extended rituximab therapy for previously untreated patients with Waldenström's macroglobulinemia indicates that this agent is active, well tolerated, and might be associated with a long period without the need for further treatment. Studies that will combine rituximab with chemotherapy or with other monoclonal antibodies might be of interest.