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

Amyloidosis and Myeloma Unit Hospital Clinic of Barcelona August Pi i Sunyer Biomedical Research Institute Barcelona Spain

Amyloidosis Research and Treatment Center Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Pavia Italy

Bologna University School of Medicine Bologna Italy

Centre Hospitalier Universitaire Hotel Dieu Nantes France

Centre Hospitalier Universitaire Limoges France

Centre Leon Berard Lyon France

Clinical Epidemiology and Biometry Service Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Pavia Italy

Department of Clinical Therapeutics National and Kapodistrian University of Athens School of Medicine Athens Greece

Department of Hemato oncology University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

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

University Hospital of Salamanca Instituto de Investigación Biosanitaria de Salamanc Institute of Cancer Molecular and Cellular Biology Salamanca Spain

University of Torino Torino Italy

Westmead Hospital Sydney New South Wales Australia

J Clin Oncol. 2020 Oct 1;38(28):3243-3244. doi: 10.1200/JCO.20.01904. PubMed

References provided by Crossref.org

The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018

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ClinicalTrials.gov
NCT01277016