Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.
In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
Bringhen
Sara
S
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria S. Giovanni Battista, Torino, Italy.
Larocca
Alessandra
A
Rossi
Davide
D
Cavalli
Maide
M
Genuardi
Mariella
M
Ria
Roberto
R
Gentili
Silvia
S
Patriarca
Francesca
F
Nozzoli
Chiara
C
Levi
Anna
A
Guglielmelli
Tommasina
T
Benevolo
Giulia
G
Callea
Vincenzo
V
Rizzo
Vincenzo
V
Cangialosi
Clotilde
C
Musto
Pellegrino
P
De Rosa
Luca
L
Liberati
Anna Marina
AM
Grasso
Mariella
M
Falcone
Antonietta P
AP
Evangelista
Andrea
A
Cavo
Michele
M
Gaidano
Gianluca
G
Boccadoro
Mario
M
Palumbo
Antonio
A
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000453:epidemiology; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone