Response assessment in <scp>W</scp>aldenström macroglobulinaemia: update from the <scp>VI</scp>th <scp>I</scp>nternational <scp>W</scp>orkshop

Owen, Roger G.; Kyle, Robert A.; Stone, Marvin J.; Rawstron, Andy C.; Leblond, Véronique; Merlini, Giampaolo; García‐Sanz, Ramón; Ocio, Enrique M.; Morra, Enrica; Morel, Pierre; Anderson, Kenneth C.; Patterson, Christopher J.; Munshi, Nikhil C.; Tedeschi, Alessandra; Joshua, Douglas; Kastritis, Efstathios; Terpos, Evangelos; Ghobrial, Irène M.; Leleu, Xavier; Gertz, Morie A.; Ansell, Stephen M.; Morice, William G.; Kimby, Eva; Treon, Steven P.

doi:10.1111/bjh.12102

Cited by 243 publications

(196 citation statements)

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“…Hematopoietic growth factors were given in all the centers. The response criteria were those agreed at the sixth WM workshop [11]. Very good partial responses (VGPR), partial responses (PR), and minor responses (MR) were defined by >90%, >50%, and 25-50% reductions in the IgM level, respectively.…”

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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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“…Effekt monitoreres først og fremst ved IgM-nivå og klinisk tilstand (199). Beinmargsbiopsi overveies etter ½ år.…”

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Brattås¹,

Reikvam²

2017

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“…1,21,22 Pearson Chi-square test, two-sided Fisher test, Mann-Whitney test, Kaplan-Meier method, and log-rank test were applied to the data in appropriate settings, using SPSS Statistics v22 (IBM), PRISM v6.0 (Graphpad), and/or R 23 software.…”

Section: Statistical Analysesmentioning

confidence: 99%

TCL1 expression patterns in Waldenström macroglobulinemia

et al. 2016

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The oncogenic role of TCL1 in chronic lymphocytic leukemia is well established in transgenic mice. TCL1 expression in other B-cell malignancies has been also described: post-germinal center-derived malignancies, such as multiple myeloma, classically do not express TCL1. Waldenström macroglobulinemia is a post-germinal center malignancy that is known to be similar to chronic lymphocytic leukemia in terms of its gene expression profile. TCL1 expression has not been so far assessed in Waldenström macroglobulinemia. Transcriptomic explorations show that TCL1A expression is linked to signaling pathways and biological functions that are known to be involved in Waldenström macroglobulinemia as well as to gene signatures of interest in B-cell malignancies. We investigated TCL1 expression at the protein level in the bone marrow of a series of 59 patients with Waldenström macroglobulinemia: 76% of patients expressed TCL1, which appeared to be associated with a pejorative prognostic impact. TCL1 could have an oncogenic role in Waldenström macroglobulinemia, and deserves further exploration.

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Response assessment in Waldenström macroglobulinaemia: update from the VIth International Workshop

Cited by 243 publications

References 33 publications

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

Ringsideroblaster

TCL1 expression patterns in Waldenström macroglobulinemia

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