Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström's Macroglobulinemia
Language English Country United States Media print-electronic
Document type Randomized Controlled Trial, Journal Article, Research Support, Non-U.S. Gov't
PubMed
36763945
DOI
10.1200/jco.22.01805
Knihovny.cz E-resources
- MeSH
- Bortezomib adverse effects MeSH
- Cyclophosphamide MeSH
- Dexamethasone MeSH
- Humans MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects MeSH
- Rituximab MeSH
- Waldenstrom Macroglobulinemia * drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Bortezomib MeSH
- Cyclophosphamide MeSH
- Dexamethasone MeSH
- Rituximab MeSH
PURPOSE: Rituximab/chemotherapy is a cornerstone of treatment for Waldenström's macroglobulinemia (WM). In addition, bortezomib has shown significant activity in WM. This study evaluated the efficacy and safety of dexamethasone, rituximab, and cyclophosphamide (DRC) as first-line treatment in WM. METHODS: In this European study, treatment-naïve patients were randomly assigned to DRC or bortezomib-DRC B-DRC for six cycles. The primary end point was progression-free survival. Secondary end points included response rates, overall survival, and safety. RESULTS: Two hundred four patients were registered. After a median follow-up of 27.5 months, the estimated 24-month progression-free survival was 80.6% (95% CI, 69.5 to 88.0) for B-DRC and 72.8% (95% CI, 61.3 to 81.3) for DRC (P = .32). At the end of treatment, B-DRC and DRC induced major responses in 80.6% versus 69.9% and a complete response/very good partial response in 17.2% versus 9.6% of patients, respectively. The median time to first response was shorter for B-DRC with 3.0 (95% CI, 2.8 to 3.2) versus 5.5 (95% CI, 2.9 to 5.8) months for DRC. This resulted in higher major response rates (57.0% v 32.5%; P < .01) after three cycles of B-DRC compared with DRC. At best response, the complete response/very good partial response increased to 32.6% for B-DRC. Both treatments were well tolerated: grade ≥ 3 adverse events occurred in 49.2% of all patients (B-DRC, 49.5%; DRC, 49.0%). Peripheral sensory neuropathy grade 3 occurred in two patients treated with B-DRC and in none with DRC. CONCLUSION: This large randomized study illustrates that B-DRC is highly effective and well tolerated in WM. The data demonstrate that fixed duration immunochemotherapy remains an important pillar in the clinical management of WM.
Centre Hospitalier Schaffner Lens Cedex 9 Lens Cedex France
CHU Amiens Hôpital Sud Amiens France
CHU Cote de Nacre Hopital de Caen Caen France
CHU Estaing Clermont Ferrand France
CHU Pontchaillou Rennes France
Department of Internal Medicine 3 University Hospital of Ulm Ulm Germany
Department of Medicine Huddinge Karolinska Institutet Unit for Hematology Stockholm Sweden
Hematology Department and CIC1402 INSERM CHU Poitiers Poitiers France
Hematology Department Institut Paoli Calmettes Marseille France
Hospital Universitario de Salamanca Salamanca Spain
Institute of Epidemiology and Medical Biometry University of Ulm Ulm Germany
Institute of Experimental Cancer Research University Hospital of Ulm Ulm Germany
Instituto Português de Oncologia de Lisboa Lisbon Portugal
Sorbonne Université Hématologie clinique Hôpital Pitié Salpêtrière APHP Paris France
References provided by Crossref.org
ClinicalTrials.gov
NCT01788020
