VMP (Bortezomib, Melphalan, and Prednisone) is active and well tolerated in newly diagnosed patients with multiple myeloma with moderately impaired renal function, and results in reversal of renal impairment: cohort analysis of the phase III VISTA study.
PURPOSE To assess bortezomib plus melphalan and prednisone (VMP) and melphalan and prednisone (MP) in previously untreated patients with multiple myeloma (MM) with renal impairment enrolled on the phase III VISTA study, and to evaluate renal impairment reversibility. PATIENTS AND METHODS Patients received nine 6-week cycles of VMP (bortezomib 1.3 mg/m(2), melphalan 9 mg/m(2), prednisone 60 mg/m(2)) or MP. Patients with serum creatinine higher than 2 mg/dL were excluded. Results In the VMP/MP arms, 6%/4%, 27%/30%, and 67%/66% of patients had baseline glomerular filtration rate (GFR) of < or = 30, 31 to 50, and higher than 50 mL/min, respectively. Response rates were higher and time to progression (TTP) and overall survival (OS) longer with VMP versus MP across renal cohorts. Response rates with VMP and TTP in both arms did not appear significantly different between patients with GFR < or = 50 or higher than 50 mL/min; OS appeared somewhat longer in patients with normal renal function in both arms. Renal impairment reversal (baseline GFR < 50 improving to > 60 mL/min) was seen in 49 (44%) of 111 patients receiving VMP versus 40 (34%) of 116 patients receiving MP. By multivariate analysis, younger age (< 75 years; P = .006) and less severe impairment (GFR > or = 30 mL/min; P = .027) were associated with higher reversal rates. In addition, treatment with VMP approached significance (P = .07). In both arms, rates of grade 4 and 5 adverse events (AEs) and serious AEs appeared higher in patients with renal impairment; with VMP, rates of discontinuations/bortezomib dose reductions due to AEs did not appear affected. CONCLUSION VMP is a feasible, active, and well-tolerated treatment option for previously untreated patients with MM with moderate renal impairment, resulting in 44% renal impairment reversal.
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, School of Medicine, Athens, Greece. mdimop@med.uoa.gr
Meletios A
MA
Dimopoulos
Paul G
PG
Richardson
Rudolf
R
Schlag
Nuriet K
NK
Khuageva
Ofer
O
Shpilberg
Efstathios
E
Kastritis
Martin
M
Kropff
Maria T
MT
Petrucci
Michel
M
Delforge
Julia
J
Alexeeva
Rik
R
Schots
Tamás
T
Masszi
Maria-Victoria
MV
Mateos
William
W
Deraedt
Kevin
K
Liu
Andrew
A
Cakana
Helgi
H
van de Velde
Jesús F
JF
San Miguel
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy*; D015999:Multivariate Analysis; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone