Bortezomib cumulative dose, efficacy, and tolerability with three different bortezomib-melphalan-prednisone regimens in previously untreated myeloma patients ineligible for high-dose therapy.
Substantial efficacy has been demonstrated with bortezomib-melphalan-prednisone in phase III studies in transplant-ineligible myeloma patients using various twice-weekly and once-weekly bortezomib dosing schedules. In VISTA, the regimen comprised four 6-week twice-weekly cycles, plus five 6-week once-weekly cycles. In the GIMEMA MM-03-05 study, the bortezomib-melphalan-prednisone regimen was either per VISTA ('GIMEMA twice-weekly'), or comprised nine 5-week once-weekly cycles ('GIMEMA once-weekly'). In the GEM2005MAS65 study, the regimen comprised one 6-week twice-weekly cycle, plus five 5-week once-weekly cycles. We evaluated the cumulative bortezomib dose administered during bortezomib-melphalan-prednisone, as well as efficacy and tolerability, using patient-level study data. Over all bortezomib-melphalan-prednisone cycles (nine in VISTA/GIMEMA; six in GEM2005MAS65), the median cumulative bortezomib dose administered was 38.5, 42.1, 40.3, and 32.9 mg/m(2) in VISTA, GIMEMA twice-weekly, GIMEMA once-weekly, and GEM2005MAS65, respectively, and the respective proportions of planned bortezomib dose actually delivered were 57.0%, 62.3%, 86.1%, and 90.4%. Response rates following bortezomib-melphalan-prednisone were 74-87% and appeared generally similar between studies. Three-year survival rates were 67.9-75.7% across studies. Grade 3/4 peripheral neuropathy rates were 13% in VISTA and 14% in GIMEMA twice-weekly, but were lower at 2% in GIMEMA once-weekly and 7% in GEM2005MAS65. Discontinuations and bortezomib dose reductions due to peripheral neuropathy were reduced in GIMEMA once-weekly versus VISTA and GIMEMA twice-weekly. Exclusive or predominant use of once-weekly bortezomib dosing in GIMEMA once-weekly and GEM2005MAS65 resulted in high efficacy, comparable with that demonstrated in VISTA, and similar cumulative bortezomib dose with reduced toxicity. Trials are registered with ClinicalTrials.gov: VISTA (Identifier:00111319), GIMEMA MM-03-05 (Identifier:01063179), and GEM2005MAS65 (Identifier:00443235).
Servicio de Hematología, Hospital Universitario de Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain mvmateos@usal.es.
María-Victoria
MV
Mateos
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista, Torino, Italy.
Sara
S
Bringhen
Dana-Farber Cancer Institute, Boston, MA, USA.
Paul G
PG
Richardson
Hospital Universitario 12 de Octubre, Madrid, Spain.
Juan Jose
JJ
Lahuerta
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista, Torino, Italy.
Alessandra
A
Larocca
Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Albert
A
Oriol
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista, Torino, Italy.
Mario
M
Boccadoro
Servicio de Hematología, Hospital Universitario de Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain.
Ramón
R
García-Sanz
Università degli Studi di Catania, Ospedale Ferrarotto, Catania, Italy.
Francesco
F
Di Raimondo
Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
Dixie-Lee
DL
Esseltine
Janssen Research & Development, Beerse, Belgium.
Helgi
H
van de Velde
Janssen Global Services, Raritan, NJ, USA.
Avinash
A
Desai
Janssen Research & Development, Horsham, PA, USA.
Anil
A
Londhe
Clinica Universidad de Navarra, Centro Investigación Medica Aplicada, Pamplona, Spain.
Jesús F
JF
San Miguel
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria (AOU) S. Giovanni Battista, Torino, Italy.
Antonio
A
Palumbo
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018450:Disease Progression; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D010523:Peripheral Nervous System Diseases / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone