Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Feb;206(2):556-564.
doi: 10.1111/bjh.19920. Epub 2024 Nov 27.

Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single-arm FIL-BRB trial

Giulia Benevolo  1 , Daniela Drandi  2 , Nicoletta Villivà  3 , Anna Castiglione  4 , Federico Monaco  5 , Carola Boccomini  6 , Daniela Dessi  7 , Catello Califano  8 , Luigi Curreli  9 , Federica Cavallo  1   2 , Annarita Conconi  10 , Gianluca Gaidano  11 , Francesca Gaia Rossi  12 , Tommaso Caravita di Toritto  3 , Martina Ferrante  2 , Donato Mannina  13 , Patrizia Tosi  14 , Giuseppe Pietrantuono  15 , Gerardo Musuraca  16 , Michele Merli  17 , Roberto Sartori  18 , Monica Tani  19 , Roberto Freilone  6 , Marzia Varettoni  20 , Simone Ferrero  1   2
Affiliations
Clinical Trial

Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single-arm FIL-BRB trial

Giulia Benevolo et al. Br J Haematol. 2025 Feb.

Abstract

This multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m2 on days 1-2), rituximab (375 mg/m2 intravenously on day 1) and bortezomib (1.3 mg/m2 sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR-WM). Moreover, MYD88L265P and CXCR4S338X mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients. Overall response rate at the end of therapy was 84.6%, including 4 (11%) complete remission, 15 (39%) very good partial response, 12 (32%) partial responses according to IWWM response criteria. At 18, 24 and 30 months, progression-free survival was 84.2% (95% CI 68.2%-92.6%), 81.5% (95%CI 65.1-90.7) and 78.8% (95%CI 62.0-88.8) respectively. At 18 months, the Overall survival was 92.1% (95%CI 77.5%-97.4%). Overall, 19 patients (50%) experienced grade 3-4 haematological toxicity, mainly thrombocytopenia, and grade 1-3 neuropathy rate was about 10% and required bortezomib dose reduction but did not result in treatment interruption. Moreover, BRB treatment induced the high rates of undetectable molecular minimal residual disease (MRD) at the end of the therapy. BRB regimen used as second line is an effective and well-tolerated salvage treatment for relapsed refractory Waldenstrom macroglobulinaemia patients. MRD monitoring showed promising efficacy in clearing the residual disease.

Keywords: Waldenstrom‐S macroglobulinaemia; chemotherapy; immunotherapy; molecular biology.

PubMed Disclaimer

References

REFERENCES

    1. Benevolo G, Nicolosi M, Santambrogio E, Vitolo U. Current options to manage Waldenström's macroglobulinemia. Expert Rev Hematol. 2017;10(7):637–647.
    1. Dogliotti I, Jiménez C, Varettoni M, Talaulikar D, Bagratuni T, Ferrante M, et al. Diagnostics in Waldenström's macroglobulinemia: a consensus statement of the European consortium for Waldenström's macroglobulinemia. Leukemia. 2023;37(2):388–395.
    1. D'Sa S, Matous JV, Advani R, Buske C, Castillo JJ, Gatt M, et al. Report of consensus panel 2 from the 11th international workshop on Waldenström's macroglobulinemia on the management of relapsed or refractory WM patients. Semin Hematol. 2023;60(2):80–89.
    1. Tedeschi A, Benevolo G, Varettoni M, Battista ML, Zinzani PL, Visco C, et al. Fludarabine plus cyclophosphamide and rituximab in Waldenstrom macroglobulinemia. Cancer. 2012;118(2):434–443.
    1. Buske C, Tedeschi A, Trotman J, García‐Sanz R, MacDonald D, Leblond V, et al. Ibrutinib plus rituximab versus placebo plus rituximab for Waldenström's macroglobulinemia: final analysis from the randomized phase III iNNOVATE study. J Clin Oncol. 2022;40(1):52–62.

Publication types

MeSH terms

LinkOut - more resources