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 Waldenstrom 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/m 2 intravenously on day 1 and cyclophosphamide 100 mg/m 2 orally bid on days 1 to 5 (total dose, 1,000 mg/m 2 ). 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. J Clin Oncol 25:3344-3349. © 2007 by American Society of Clinical Oncology