Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.

Leblond, Véronique; Ben-Othman, T; Deconinck, Eric; Taksin, Anne‐Laure; Harousseau, J L; Delgado, M. A. Tarilonte; Delmer, Alain; Maloisel, Frédéric; Mariette, Xavier; Morel, Philippe; Clauvel, J. P.; Duboisset, P; Entezam, S; Hermine, Olivier; M, Merlet; Yakoub-Agha, Ibrahim; Guibon, Odile; Caspard, Hervé; Fort, N

doi:10.1200/jco.1998.16.6.2060

Cited by 84 publications

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“…Alkylating agents and then purine analogues, initially used as single-agent treatments, gave an ORR between 50 and 75%, and 40 and 80%, respectively [13][14][15][16]. However, few patients entered complete remission, responses were short-lived, and progression-free survival was poor.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

et al. 2016

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Waldenstrom's macroglobulinemia is generally treated with alkylating agents, purine analogs and monoclonal antibodies, alone or in combination. We report the outcomes of 82 patients (median age 61 years) treated with the RFC combination. Twenty-five patients were treatment-naive. RFC was administered every 4 weeks, for a median of five cycles. At treatment discontinuation, the overall response rate was 85.4%. The responses improved after treatment discontinuation in 25 patients, with a median time to best response achievement of 10.8 months, raising the major response rate (PR, VGPR and CR) from 64.6% to 76.8%. With a median follow-up of 47 months, the median progression-free survival time had not been reached (67% PFS at 48 months) and was influenced by age and treatment status before RFC. Likewise, the median time to next therapy had not been reached. Two cases of myelodysplastic syndrome/AML and 3 cases of transformation to aggressive lymphoma occurred. Thirteen patients died. The 3-year overall survival rate was 90%. Long-lasting cytopenias occurred in 19 patients. The RFC combination thus gave a high response rate and durable responses, even in heavily treatment-experienced patients. The high incidence of long-lasting cytopenia might be reduced by giving fewer courses and thereby minimizing myelotoxicity. Waldenstrom's macroglobulinemia (WM) is a rare B-cell malignancy characterized by the production of a monoclonal immunoglobulin (IgM) by welldifferentiated plasmacytic lymphocytes. Therapy is currently reserved for patients with constitutional symptoms, bone marrow or peripheral lymphoid organ involvement, and complications due to the monoclonal IgM component [1]. There is no consensus treatment strategy, and most clinical trials in WM have so far consisted of small phase II studies with widely differing inclusion and response criteria. Classically used chemotherapeutic agents consist of alkylating agents (chlorambucil, cyclophosphamide), purine analogues (fludarabine, 2-chlorodeoxyadenosine or 2CDA), a proteasome inhibitor (bortezomib) and bendamustine, used either alone or, more often, combined with immunotherapy (principally rituximab). A combination of cyclophosphamide and purine analogues offers synergistic activity, as DNA breaks caused by cyclophosphamide cannot be repaired in the presence of a purine analogue [2]. Studies of the cyclophosphamide and fludarabine combination in WM patients showed an overall response rate (ORR) of 55-77%, and a median time to treatment failure of around 24 months [3]. The fludarabine and rituximab combination has also been studied in a phase II trial, with an ORR of 95.3%, a 4-year progression-free survival rate (PFS) of 67%, and a median time to progression (TTP) of 77 months [4]. Rituximab, fludarabine, and cyclophosphamide combination therapy (RFC) yields a high response rate in patients with chronic lymphocytic leukemia (CLL), both as first-line treatment and after relapse [5,6], and is more effective than the FC combination in untreated CLL patients [7]. Until no...

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confidence: 99%

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

et al. 2016

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“…8 In small preliminary studies, promising clinical activity of both FAMP and 2-CDA in WM was observed. [8][9][10][11][12][13][14][15] In 1992, the Southwest Oncology Group (SWOG) began a prospective clinical trial to examine the natural history of WM and evaluate the clinical activity of FAMP in untreated patients as well as those who had previously undergone alkylating agent-based therapy. We present the results of this first large intergroup clinical trial in patients with WM.…”

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confidence: 99%

Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003)

Dhodapkar

Jacobson

Gertz

et al. 2001

Blood

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“…Purine analogs may yield higher response rates when used as first-line therapy. [3][4][5] The combination of FDR with cyclophosphamide (Cy) gives an 80% response rate in untreated indolent malignancies such as CLL 6,7 and a 30% response rate in previously treated patients. 8 Recently, the German CLL group reported a better response rate and response duration in patients treated with FDR plus Cy than in those treated with FDR alone in a randomized phase III study.…”

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Fludarabine plus cyclophosphamide in Waldenström's macroglobulinemia: results in 49 patients

et al. 2005

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Activity of fludarabine in previously treated Waldenström's macroglobulinemia: a report of 71 cases. Groupe Coopératif Macroglobulinémie.

Abstract: The responses rate in this population with a poor prognosis is close to that reported in shorter series. Patients with WM who are resistant to alkylating agents should be identified early, so that salvage therapy with nucleoside analogs can be started without delay.

Cited by 84 publications

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Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

Efficacy and long‐term toxicity of the rituximab‐fludarabine‐cyclophosphamide combination therapy in Waldenstrom's macroglobulinemia

Prognostic factors and response to fludarabine therapy in patients with Waldenström macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003)

Fludarabine plus cyclophosphamide in Waldenström's macroglobulinemia: results in 49 patients

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