136 • Clinical Lymphoma & Myeloma September 2005 Introduction At present, Waldenström’s macroglobulinemia (WM) remains incurable, with a median survival of 5 years reported for patients treated with alkylator agent–based chemotherapy. 1,2 The purine analogues cladribine and fludarabine show considerable activity, with response rates (RRs) of 57%-94% 3-6 and 40%-79%, 7-9 respectively, in previously untreated WM; however, in phase II studies, the front-line use of these agents does not appear to have exhibited any significant improvement in remission duration 3,5-7,9 or overall survival (OS) 6,9 when retrospectively compared with oral chlorambucil alone. 1,2,10 Moreover, results in the salvage therapy setting remain inadequate, with RRs of < 50% in most studies 4,8,9,11-16 for single-agent cladribine and fludarabine, although the latter is superior to cyclophosphamide/doxorubicin/prednisone in a phase III trial. 14 Based on in vitro 17,18 and clinical evidence 19,20 of synergistic cytotoxicity, we explored the use fludarabine/mitoxantrone (FM) or fludarabine/cyclophosphamide (FC) in patients with untreated WM and relapsed/refractory WM. Moreover, the demonstration of significant single-agent activity of rituximab in WM 21,22 and the promising results of fludarabine/rituximab–based chemoimmunotherapy in other indolent lymphoid disorders 23-25 led to rituximab’s inclusion with FC (FCR). Herein, we present our results of 18 treatment cycles in 16 patients treated with FC (n = 9), FM (n = 3), FCR (n = 5), and/or fludarabine/rituximab (FR; n = 1). Patients and Methods This retrospective analysis was based on patients treated with fludarabine combination therapy at the Peter MacCallum Cancer Centre between December 1994 and March 2004: FM (fludarabine 25 mg/m 2 intravenously [I.V.] days 1-3 plus mitoxantrone 10 mg/m 2 I.V. on day 1), 20 FC (fludarabine 25 mg/m 2 Fludarabine Combination Therapy Is Highly Effective in First-Line and Salvage Treatment of Patients with Waldenström’s Macroglobulinemia Constantine S.Tam, 1,2 Max M.Wolf, 1 David Westerman, 1 E. Henry Januszewicz, 1 H. Miles Prince, 1 John F. Seymour 1 Alkylating agents or single-agent purine analogues are modestly effective as front-line therapy for Waldenström’s macroglobulinemia (WM), but response rates of < 50% are exhibited in the salvage therapy setting. Fludarabine combination therapy may be more effective, but no large studies exploring these regimens specifically in WM are available. We report our results of 18 cycles of fludarabine combi- nation therapy: FC (fludarabine 25 mg/m 2 for 3 days plus cyclophosphamide 250 mg/m 2 for 3 days; n = 9), FM (fludarabine 25 mg/m 2 for 3 days plus mitoxantrone 10 mg/m 2 for 1 day; n = 3), FCR (FC plus rituximab 375 mg/m 2 ; n = 5), or fludarabine/rituximab (n = 1). Four patients had previously untreated disease, and 14 had pretreated disease; 67% had elevated serum levels of β 2 -microglobulin, and 86% had hemoglobin levels ≤ 12 g/dL. Patients received a median of 4 cycles (range, 1-6 cycles), with grade ≥ 3 neutropenia and infec- tion complicating 25% and 4% of cycles, respectively. Objective responses (all partial) were attained in 13 patients (76%). Response rates did not significantly differ by regimen, previous treatment, age, performance status, β 2 -microglobulin level, hemoglobin level, time from diagnosis, previous fludarabine exposure, or alkylator refractoriness. Median remission duration was 38 months; no previously untreat- ed patient had died at a median of 37 months of follow-up, and the actuarial 5-year survival rate was 55% for pretreated patients. No cases of secondary myelodysplasia or leukemia were encountered. Clinical Lymphoma & Myeloma, Vol. 6, No. 2, 136-139, 2005 Key words: Cyclophosphamide, Lymphoplasmacytic lymphoma, Mitoxantrone, Purine analogues, Rituximab Abstract Brief Communication Address for correspondence: John F. Seymour, MBBS, Head of Leukaemia/Lymphoma Service, Department of Haematology, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett St, Victoria 8006, Australia Fax: 613-9656-1408; e-mail: john.seymour@petermac.org Submitted: Apr 18, 2005; Revised: Jul 19, 2005; Accepted: Jul 22, 2005 1 Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia 2 Department of Haematology, the Alfred Hospital, Prahran, Victoria, Australia Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1526-9655, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.