Efficacy and safety of bortezomib in patients with renal impairment: Results from the APEX phase 3 study

J. F. San-Miguel*, P. G. Richardson, P. Sonneveld, M. W. Schuster, D. Irwin, E. A. Stadtmauer, T. Facon, J. L. Harousseau, D. Ben-Yehuda, S. Lonial, H. Goldschmidt, D. Reece, J. Bladé, M. Boccadoro, J. D. Cavenagh, R. Neuwirth, A. L. Boral, D. L. Esseltine, K. C. Anderson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

168 Scopus citations


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 >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 >50 vs >50ml 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 >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.

Original languageAmerican English
Pages (from-to)842-849
Number of pages8
Issue number4
StatePublished - Apr 2008
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development LLC. We thank Steve Hill and Rosemary Washbrook for their assistance in drafting the manuscript. Steve Hill is a medical writer and Rosemary Washbrook is a medical editor with Gardiner-Caldwell London. We also thank the APEX Management Team; Dalton W, Anderson K, Harousseau J and San-Miguel J and the APEX Investigators; Abubakr Y, Agura E, Alexanian R, Alsina M, Andre M, Attal M, Avigan D, Baccarani M, Bahlis N, Barbui T, Barton, K, Belch A, Bensinger W, Ben-Yehuda D, Berdeja J, Bjorkstrand B, Bladé J, Boccadoro M, Boue F, Bourhis J, Bron D, Catlett J, Cavenagh J, Cavet J, Chanan-Khan A, Coiffier B, Comenzo R, Craddock C, Dearden C, Delforge M, Densmore J, Doyen C, Durk H, Ehninger G, Einsele H, Engelhardt M, Facon T, Fay J, Fehrenbacher L, Feremans W, Fermand JP, Fernandez H, Giguere J, Glasmacher A, Glass J, Goldschmidt H, Gordon P, Gramatzki M, Gruber A, Gyan E, Hamm J, Hegewisch-Becker S, Huber C, Hulin C, Hussein M, Ifthikharuddin J, Irwin D, Jackson G, Jagannath S, Jagasia M, Jakubowiak A, Klein A, Kobbe G, Kovacs M, Krishnan A, Kropff M, Kuter D, Lacy M, Lenhoff S, Limentani S, Lokhorst H, Lonial S, Ludwig H, Mandelli F, Marie JP, Marsden GJ, Martin T, Mason J, Mavromatis B, Morris C, Morrison V, Nowrousian M, Orlowski R, Pecora A, Phelan J, Posada, J, Rahemtulla A, Rai K, Reece D, Richardson P, Rowe JM, Schilder R, Schmidt W, Schuster M, Sezer O, Shadduck R, Shustik C, Siegel D, Singhal S, Sonneveld P, Sotto JJ, Stadtmauer E, Tarantolo S, Van Droogenbroeck J, Van Oers MH, Vellenga E, Vesole D, Vij R, Zachee P and Zangari M.


Dive into the research topics of 'Efficacy and safety of bortezomib in patients with renal impairment: Results from the APEX phase 3 study'. Together they form a unique fingerprint.

Cite this