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.