Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenstrom macroglobulinemia in first relapse or with primary refractory disease

Few reports are available on the treatment of patients with Waldenstrom mac roglobulinemia (WM) and primary or secondary resistance to alkylating-agent -based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after a lkylating-agent therapy were randomly assigned to receive fludarabine (25 m g/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin ( Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m( 2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first e nd point evaluated was the response rate after 6 treatment courses. Forty-f ive patients received CAP and 45 received fludarabine. Two patients died be fore the first course of chemotherapy. No statistical differences were obse rved between the 2 treatment arms with respect to hematologic toxicity or I nfections. Mucositis and alopecia occurred significantly more often in pati ents treated with CAP Partial responses were obtained In 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P = .019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly highe r in this group (P < .01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the m edian overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents. (C) 2001 by The American Society of Hematology.