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Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis
E. Kastritis, X. Leleu, B. Arnulf, E. Zamagni, MT. Cibeira, F. Kwok, P. Mollee, R. Hájek, P. Moreau, A. Jaccard, SO. Schönland, R. Filshie, E. Nicolas-Virelizier, B. Augustson, MV. Mateos, A. Wechalekar, E. Hachulla, P. Milani, MA. Dimopoulos,...
Language English Country United States
Document type Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
32730181
DOI
10.1200/jco.20.01285
Knihovny.cz E-resources
- MeSH
- Administration, Oral MeSH
- Bortezomib administration & dosage adverse effects MeSH
- Dexamethasone administration & dosage adverse effects MeSH
- Progression-Free Survival MeSH
- Middle Aged MeSH
- Humans MeSH
- Melphalan administration & dosage adverse effects MeSH
- Immunoglobulin Light-chain Amyloidosis drug therapy pathology MeSH
- Antineoplastic Combined Chemotherapy Protocols adverse effects therapeutic use MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
PURPOSE: Oral melphalan and dexamethasone (MDex) were considered a standard of care in light-chain (AL) amyloidosis. In the past decade, bortezomib has been increasingly used in combination with alkylating agents and dexamethasone. We prospectively compared the efficacy and safety of MDex and MDex with the addition of bortezomib (BMDex). METHODS: This was a phase III, multicenter, randomized, open-label trial. Patients were stratified according to cardiac stage. Patients with advanced cardiac stage (stage IIIb) amyloidosis were not eligible. The primary end point was hematologic response rate at 3 months. This trial is registered with ClinicalTrials.gov identifier NCT01277016. RESULTS: A total of 109 patients, 53 in the BMDex and 56 in the MDex group, received ≥ 1 dose of therapy (from January 2011 to February 2016). Hematologic response rate at 3 months was higher in the BMDex arm (79% v 52%; P = .002). Higher rates of very good partial or complete response rates (64% v 39%; hazard ratio [HR], 2.47; 95% CI, 1.30 to 4.71) and improved overall survival, with a 2-fold decrease in mortality rate (HR, 0.50; 95% CI, 0.27 to 0.90), were observed in the BMDex arm. Grade 3 and 4 adverse events (the most common being cytopenia, peripheral neuropathy, and heart failure) were more common in the BMDex arm, occurring in 20% versus 10% of cycles performed. CONCLUSION: BMDex improved hematologic response rate and overall survival. To our knowledge, this is the first time a controlled study has demonstrated a survival advantage in AL amyloidosis. BMDex should be considered a new standard of care for AL amyloidosis.
Aalborg University Hospital Aalborg Denmark
Bologna University School of Medicine Bologna Italy
Centre Hospitalier Universitaire Hotel Dieu Nantes France
Centre Hospitalier Universitaire Limoges France
Centre Leon Berard Lyon France
Department of Molecular Medicine University of Pavia Pavia Italy
Erasmus MC Cancer Institute Rotterdam the Netherlands
Hopital Huriez Centre Hospitalier Régional Universitaire Lille France
Immunohematology Unit Hospital Saint Louis Assistance Publique Hôpitaux de Paris Paris France
Medical Department 5 Amyloidosis Centre University Hospital Heidelberg Germany
Princess Alexandra Hospital and University of Queensland Brisbane Queensland Australia
Sir Charles Gairdner Hospital Perth Western Australia Australia
St Vincent's Hospital Melbourne Victoria Australia
University College London Medical School Royal Free Hospital Campus London United Kingdom
References provided by Crossref.org
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