TY - JOUR
T1 - Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis
AU - Kastritis, Efstathios
AU - Leleu, Xavier
AU - Arnulf, Bertrand
AU - Zamagni, Elena
AU - Cibeira, María Teresa
AU - Kwok, Fiona
AU - Mollee, Peter
AU - Hájek, Roman
AU - Moreau, Philippe
AU - Jaccard, Arnaud
AU - Schönland, Stefan O
AU - Filshie, Robin
AU - Nicolas-Virelizier, Emmanuelle
AU - Augustson, Bradley
AU - Mateos, María-Victoria
AU - Wechalekar, Ashutosh
AU - Hachulla, Eric
AU - Milani, Paolo
AU - Dimopoulos, Meletios A
AU - Fermand, Jean-Paul
AU - Foli, Andrea
AU - Gavriatopoulou, Maria
AU - Klersy, Catherine
AU - Palumbo, Antonio
AU - Sonneveld, Pieter
AU - Johnsen, Hans Erik
AU - Merlini, Giampaolo
AU - Palladini, Giovanni
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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 5 .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.
AB - 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 5 .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.
UR - http://www.scopus.com/inward/record.url?scp=85091956865&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.01285
DO - 10.1200/JCO.20.01285
M3 - Journal article
C2 - 32730181
SN - 0732-183X
VL - 38
SP - 3252
EP - 3260
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 28
ER -