Fludarabine Based Combinations Are Highly Effective as First-Line or Salvage Treatment in Patients with Waldenström Macroglobulinemia

Treatment with single agent rituximab (R), alkylating agents or purine analogues is safe and moderately effective as first-line treatment for patients (pts) with Waldenstrom Macroglobulinemia (WM). However, efficacy in relapsed/refractory WM is unsatisfactory. We analysed if combinations of fludarabine (F) with alkylators and/or R were safe and more effective. From 12/94 - 08/08, 25 courses of at least 2 cycles of intravenous F-combination therapy were administered to 22 pts with WM: FC (F 25mg/m 2 d1–3, cyclophosphamide (C) 250mg/m 2 d1–3; n=7); FCR (FC+R 375mg/m 2 d1; n=14); FM (F+mitoxantrone (M) 10mg/m 2 d1; n=3); FR, n=1). The median age of pts was 57yrs [range; 36–89], 18/22 (84%) male, 6 pts received F-combination as their primary treatment (24% of courses). The 19 pre-treated pts had a median number of 2 [1–7] prior treatments, prior F-exposure in 5 cases (20%), 9 pts (36%) were alkylator-refractory. The median time from diagnosis to F-based treatment was 23 Mo [0–153], baseline paraprotein (PP) 30g/L [7–64]. A total of 99 cycles were administered, median 4 [2–6] per pt. Treatment was generally well tolerated with 5% infusion reactions grade (G) 2, gastro-intestinal toxicity was mostly limited to G 1 or 2 (35% of cycles) with only one G3 episode, no renal toxicity or hepatic side effects > G 1. G 3 thrombocytopenia occurred in 5%, G ≥ 3 neutropenia and infections complicated 20% and 3% of cycles, respectively, none of which were life-threatening. However, 3 heavily pre-treated pts subsequently developed secondary AML/MDS (1 fatal) at 52, 61 and 99 Mo post-treatment. The overall response rate (RR) was 21/25 (84%) with a median PP reduction of 90% [30–100%]. One pt achieved a complete remission, 17/25 (68%) had a partial response, resulting in an objective RR of 72%, 3 responses (12%) were minor (PP-reduction of 25– 60 years or increased baseline beta 2 microglobulin impacted on EFS or OS. Anemia (Hb