Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single‐arm <scp>FIL</scp>‐<scp>BRB</scp> trial
This multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m<sup>2</sup> on days 1-2), rituximab (375 mg/m<sup>2</sup> intravenously on day 1) and bortezomib (1.3 mg/m<sup>2</sup> 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, MYD88<sup>L265P</sup> and CXCR4<sup>S338X</sup> 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.
Authors
- Francesca Gaia Rossi (ORCID: https://orcid.org/0000-0003-1428-1838)
- Simone Ferrero (ORCID: https://orcid.org/0000-0002-9711-1502)
- Roberto Freilone (ORCID: https://orcid.org/0000-0002-6003-3328)
- Monica Tani (ORCID: https://orcid.org/0000-0002-5016-2054)
- Giuseppe Pietrantuono (ORCID: https://orcid.org/0000-0002-5663-0648)
- Nicoletta Villivà
- Donato Mannina (ORCID: https://orcid.org/0000-0001-8665-1258)
- Federico Monaco (ORCID: https://orcid.org/0000-0002-4630-753X)
- Giulia Benevolo (ORCID: https://orcid.org/0000-0002-3200-9654)
- Carola Boccomini (ORCID: https://orcid.org/0000-0002-4155-403X)
- Annarita Conconi (ORCID: https://orcid.org/0000-0002-1966-4339)
- Gianluca Gaïdano (ORCID: https://orcid.org/0000-0002-4681-0151)
- Patrizia Tosi (ORCID: https://orcid.org/0000-0003-3247-4318)
- Roberto Sartori (ORCID: https://orcid.org/0000-0001-6917-0057)
- Daniela Drandi (ORCID: https://orcid.org/0000-0003-1825-1206)
- Tommaso Caravita di Toritto
- Michele Merli (ORCID: https://orcid.org/0000-0002-0905-5927)
- Marzia Varettoni (ORCID: https://orcid.org/0000-0001-7304-1629)
- Gerardo Musuraca (ORCID: https://orcid.org/0000-0003-1947-1032)
- Catello Califano (ORCID: https://orcid.org/0000-0001-5633-4657)
- Martina Ferrante (ORCID: https://orcid.org/0000-0002-1336-9603)
- Anna Castiglione (ORCID: https://orcid.org/0000-0002-3415-3617)
- Federica Cavallo (ORCID: https://orcid.org/0000-0003-2047-1099)
- Daniela Dessì
- Luigi Curreli
Institutions
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Ospedale degli Infermi (IT)
- ASL Roma (IT)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Istituto Oncologico Veneto (IT)
- Ospedale Santa Maria (IT)
- Presidio Ospedaliero (IT)
- Centro di Riferimento Oncologico (IT)
- Ospedale Infermi di Rimini (IT)
- Ospedale Castelfranco Veneto (IT)
- Fondazione Centro Marino Internazionale (IT)
- Piedmont Reference Center for Epidemiology and Cancer Prevention (IT)
- Policlinico San Matteo Fondazione (IT)
- Ospedale degli Infermi (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo (IT)
- Azienda Sanitaria Locale Roma 3 (IT)
- Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte (IT)
- Aziende Socio Sanitarie Territoriale dei Sette Laghi
- University of Turin (IT)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1111/bjh.19920
- Citations
- 2
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.88