Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3.
Total therapy 3 incorporated bortezomib into a melphalan-based tandem transplant regimen for 303 newly diagnosed patients with myeloma. Induction chemotherapy prior to and consolidation chemotherapy after transplants each consisted of two cycles of VTD-PACE (bortezomib, thalidomide, dexamethasone and 4-d continuous infusions of cis-platin, doxorubicin, cyclophosphamide, etoposide); 3-year maintenance comprised monthly cycles of VTD in the first and TD in the remaining years. The median age was 59 years (age >64 years, 28%). A minimum of 20 x 10(6) CD34 cells/kg was collected in 87% of patients; 83% completed both transplants, and only 5% suffered a treatment-related death. At 24 months, 83% had achieved near-complete remission, which was sustained in 88% at 2 years from its onset. With a median follow-up of 20 months, 2-year estimates of event-free and overall survival were 84% and 86% respectively. The 44 patients who experienced an event more often had a high-risk gene array profile, cytogenetic abnormalities and indicators of high lactate dehydrogenase, beta-2-microglobulin, creatinine and International Staging System stage. Toxicities of grade > 2 included thrombo-embolic events in 27% and peripheral neuropathy in 12%. Results of this phase-2 study demonstrated that bortezomib could be safely combined with multi-agent chemotherapy, effecting near-complete remission status and 2-year survival rates in more than 80% of patients.
Barlogie
Bart
B
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. hebertkahlan@uams.edu
Anaissie
Elias
E
van Rhee
Frits
F
Haessler
Jeffrey
J
Hollmig
Klaus
K
Pineda-Roman
Mauricio
M
Cottler-Fox
Michele
M
Mohiuddin
Abid
A
Alsayed
Yazan
Y
Tricot
Guido
G
Bolejack
Vanessa
V
Zangari
Maurizio
M
Epstein
Joshua
J
Petty
Nathan
N
Steward
Douglas
D
Jenkins
Bonnie
B
Gurley
Jennifer
J
Sullivan
Ellen
E
Crowley
John
J
Shaughnessy
John D
JD
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D003131:Combined Modality Therapy / Q000379:methods; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D033581:Stem Cell Transplantation / Q000379:methods; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D008558:Melphalan