Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study.
Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplantation is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase 1/2 trial in 60 untreated MM patients aged at least 65 years (half older than 75 years) was designed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CRs, of whom half of the IF- CR patients analyzed achieved immunophenotypic remission (no detectable plasma cells at 10(-4) to 10(-5) sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP--notably, response rate (89% versus 42%), event-free survival at 16 months (83% versus 51%), and survival at 16 months (90% versus 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy and were more evident during early cycles and in patients aged 75 years or more. In conclusion, in elderly patients ineligible for transplantation, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CRs, even in patients with poor prognostic features.
Mateos
María-Victoria
MV
Hematology Division, Grupo Español de MM, Spain. Paseo San Vicente 58-182; 37007 Salamanca, Spain.
Hernández
José-M
JM
Hernández
Miguel-T
MT
Gutiérrez
Norma-C
NC
Palomera
Luis
L
Fuertes
Marta
M
Díaz-Mediavilla
Joaquín
J
Lahuerta
Juan-J
JJ
de la Rubia
Javier
J
Terol
María-José
MJ
Sureda
Ana
A
Bargay
Joan
J
Ribas
Paz
P
de Arriba
Felipe
F
Alegre
Adrian
A
Oriol
Albert
A
Carrera
Dolores
D
García-Laraña
José
J
García-Sanz
Ramón
R
Bladé
Joan
J
Prósper
Felipe
F
Mateo
Gemma
G
Esseltine
Dixie-Lee
DL
van de Velde
Helgi
H
San Miguel
Jesús-F
JF
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D016130:Immunophenotyping; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage*; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone