What is the mechanism of injury of carfilzomib induced renal injury?
Carfilzomib (Kyprolis, Onyx) is a next-generation epoxyketone proteasome inhibitor that is approved for the treatment of relapsed refractory multiple myeloma. The phase 2 trial that initially raised interest in this agent was a single-arm study of patients with refractory multiple myeloma who received carfilzomib 20 mg/m2 intravenously twice weekly for 3 weeks in cycle 1 and then 27 mg/m2 for subsequent cycles. Increased serum creatinine was the most frequently reported renal adverse event, affecting 25% of the 266 patients in this study.
Case report and discussions with experts suggests its more likely to be a pre-renal insult. Glomerular disease is less likely the cause of the renal toxicity. In a patient who has multiple myeloma with renal involvement, nephrotoxicity caused by the disease can be hard to distinguish from nephrotoxicity caused by an agent.