Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma.
In multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 patients who received VMPT as second-line treatment, the PR rate was 79% and the immunofixation-negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.
Palumbo
Antonio
A
Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera (AO) S. Giovanni Battista, Turin, Italy. appalumbo@yahoo.com
Ambrosini
Maria Teresa
MT
Benevolo
Giulia
G
Pregno
Patrizia
P
Pescosta
Norbert
N
Callea
Vincenzo
V
Cangialosi
Clotilde
C
Caravita
Tommaso
T
Morabito
Fortunato
F
Musto
Pellegrino
P
Bringhen
Sara
S
Falco
Patrizia
P
Avonto
Ilaria
I
Cavallo
Federica
F
Boccadoro
Mario
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D012449:Safety; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone