American Society of Clinical Oncology, Journal of Clinical Oncology, 15_suppl(30), p. e18569-e18569, 2012
DOI: 10.1200/jco.2012.30.15_suppl.e18569
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e18569 Background: Patients (pts) with multiple myeloma (MM) are vulnerable to renal injury and impairment both from their disease and treatment-related adverse events (AEs). Carfilzomib (CFZ) is a selective proteasome inhibitor with proven efficacy in MM. Safety data have been compiled from over 700 pts who have received single-agent CFZ. All were pretreated and included individuals with varying degrees of renal function, including hemodialysis pts. Herein we present an analysis of the incidence and severity of CFZ treatment-emergent renal events from 526 pts in four phase 2 trials. Methods: Pts from the 003-A0, 003-A1, 004, and 005 trials were included in this analysis. In all studies, CFZ was dosed on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle (C). Doses were 20 mg/m2 in C1 for all studies escalating to 27 mg/m2 in C2 per individual protocol, except 005 (15 mg/m2 in C1, 20 mg/m2 in C2, and 27 mg/m2 in C3). Renal AEs—the incidence, frequency, and resolution of episodes of worsening renal function, defined minimally as a doubling of serum creatinine from baseline—and shifts in other laboratory parameters were tabulated and summarized based on NCI CTCAE v.3 criteria. Results: The majority of pts (71%) had renal dysfunction (CrCl <50 mL/min) at baseline. Overall, 87% experienced no significant worsening of renal function during the course of treatment. Transient worsening was reported in 31 pts (6%) with a median duration of 1.4 weeks and a median of 1.0 episode per patient; non-transient worsening was reported in 37 pts (7%) with 8 (2%) of those permanently discontinuing treatment due to a renal dysfunction AE. 38 patients (7.2%) experienced Grade 3/4 acute renal failure, of which 31 were Grade 3. The percentage of patients in 003-A0, 003-A1, and 004 whose creatinine levels shifted to Grade 3 or 4 from any lower grade was <5%. Results from 005 showed no major PK differences in pts with a wide range of renal function. Conclusions: Treatment-emergent renal events resulting in CFZ discontinuation were uncommon. Based on the findings from this cross trial analysis, CFZ dose and schedule need not be adjusted in pts with baseline renal dysfunction, including pts on hemodialysis.