title: Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study.
abstract: 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.
authors.affiliation: Department of Hematology, Hospital Universitario. CIC Universidad de Salamanca-CSIC, Salamanca, Spain. sanmigiz@usal.es
authors.forename: J F
authors.initials: JF
authors.lastname: San-Miguel
authors.forename: P G
authors.initials: PG
authors.lastname: Richardson
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.forename: M W
authors.initials: MW
authors.lastname: Schuster
authors.forename: D
authors.initials: D
authors.lastname: Irwin
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: T
authors.initials: T
authors.lastname: Facon
authors.forename: J-L
authors.initials: JL
authors.lastname: Harousseau
authors.forename: D
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: S
authors.initials: S
authors.lastname: Lonial
authors.forename: H
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: D
authors.initials: D
authors.lastname: Reece
authors.forename: J
authors.initials: J
authors.lastname: Bladé
authors.forename: M
authors.initials: M
authors.lastname: Boccadoro
authors.forename: J D
authors.initials: JD
authors.lastname: Cavenagh
authors.forename: R
authors.initials: R
authors.lastname: Neuwirth
authors.forename: A L
authors.initials: AL
authors.lastname: Boral
authors.forename: D-L
authors.initials: DL
authors.lastname: Esseltine
authors.forename: K C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone