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Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study.
San-Miguel, J F 1; Richardson, P G 2; Sonneveld, P 3; Schuster, M W 4; Irwin, D 5; Stadtmauer, E A 6; Facon, T 7; Harousseau, J-L 8; Ben-Yehuda, D 9; Lonial, S 10; Goldschmidt, H 11; Reece, D 12; Blade, J 13; Boccadoro, M 14; Cavenagh, J D 15; Neuwirth, R 16; Boral, A L 16; Esseltine, D-L 16; Anderson, K C 2
[Article] Leukemia. 22(4):842-849, April 2008.

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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 > 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 <=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.