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Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia

de Tute, Ruth; Counsell, Nicholas; Clifton-Hadley, Laura; D'Sa, Shirley; Pratt, Guy; Campbell, Gavin; Campbell, Lauren; ... Auer, Rebecca; + view all (2024) Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia. Leukemia , 38 pp. 822-828. 10.1038/s41375-024-02162-5. Green open access

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Abstract

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrőm macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response. Sixty treatment-naïve WM patients were enroled into this phase II trial and randomised (2:1) to receive cyclophosphamide and rituximab with either bortezomib (BRC) or fludarabine (FCR). The primary objective was to assess the overall response rate (ORR) in eligible patients receiving BRC (N = 41). An ORR of 97.6% (95%CI:87.1–99.9) was observed; 27 (65.9%) patients remain alive without progression after 62.6 months median follow-up, with 2-, 3- and 5-year progression-free survival (PFS) rates of 92.7% (95%CI:79.0–97.6), 80.5% (95%CI:64.8–89.7) and 65.5% (95%CI:48.8–77.9). Persistent WM B-cells were demonstrable in 19/38 patients at the end of treatment (median 0.24%, range 0.02–11.2%). PFS was markedly longer in patients with BM B-cell depletion (<0.004%) compared to those who had persistent BM B-cells detectable at end of treatment (HR = 0.06, 95%CI:0.01–0.47, p < 0.001), and remained independently associated after adjusting for baseline risk stratification or investigator-assessed response. BRC is a tolerable, highly efficacious regimen for treatment-naïve WM patients. BM B-cell depletion is independently associated with patient outcomes.

Type: Article
Title: Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41375-024-02162-5
Publisher version: https://doi.org/10.1038/s41375-024-02162-5
Language: English
Additional information: This version is the author-accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: B-cell lymphoma, Combination drug therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
URI: https://discovery.ucl.ac.uk/id/eprint/10188763
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