Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study.
Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) <30, 30-50, 51-80 and >80 ml min(-1)). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl < or =50 ml min(-1) (severe-to-moderate) and >50 ml min(-1) (no/mild impairment). Response rates with bortezomib were similar (36-47%) and time to response rapid (0.7-1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl < or =50 vs >50 ml min(-1) (P=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl < or =50 vs >50 ml min(-1). These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.
San-Miguel
J F
JF
Department of Hematology, Hospital Universitario. CIC Universidad de Salamanca-CSIC, Salamanca, Spain. sanmigiz@usal.es
Richardson
P G
PG
Sonneveld
P
P
Schuster
M W
MW
Irwin
D
D
Stadtmauer
E A
EA
Facon
T
T
Harousseau
J-L
JL
Ben-Yehuda
D
D
Lonial
S
S
Goldschmidt
H
H
Reece
D
D
Bladé
J
J
Boccadoro
M
M
Cavenagh
J D
JD
Neuwirth
R
R
Boral
A L
AL
Esseltine
D-L
DL
Anderson
K C
KC
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D001897:Boronic Acids / Q000008:administration & dosage* / Q000633:toxicity; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D011719:Pyrazines / Q000008:administration & dosage* / Q000633:toxicity; D051437:Renal Insufficiency / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone