Abstract: FR-PO280
A Case of Acute Interstitial Nephritis Associated with Belvarafenib, a Novel pan-RAF Kinase Inhibitor for Metastatic NRAS Mutant Melanoma
Session Information
- Onconephrology: From AKI to CKD and Everything in Between
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Abu Amer, Nabil, University Health Network, Toronto, Ontario, Canada
- Avila-Casado, Carmen, University Health Network, Toronto, Ontario, Canada
- Kitchlu, Abhijat, University Health Network, Toronto, Ontario, Canada
Introduction
Belvarafenib is a potent oral type II pan-RAF kinase inhibitor that inhibits B-Raf V600E- and C-Raf-mediated signal transduction pathways and mutated Ras proteins, thereby demonstrating growth suppression of cancer with RAF or RAS mutation. This novel therapy has limited known adverse effects, with no reported kidney-related adverse events. Here, we present a case of interstitial nephritis associated with Belvarafenib treatment.
Case Description
A 79-year-old woman was diagnosed with stage IV melanoma (wild-type BRAF) with NRAS mutation on the pan-RAF agent (Belvarafenib). Eight months into the treatment, she presented to the melanoma clinic with nausea, fatigue, and severe weakness. The patient was pale on physical examination, and her vital signs were normal. Laboratory investigations revealed a serum creatinine of 260 μmol/L (from baseline 90 μmol/L) and protein trace in urinalysis with no leukocyturia or hematuria. Urine microscopy showed granular casts consistent with acute tubular necrosis. The kidney function was not improved despite hydration and discontinuing Belvarafanib. A kidney core biopsy revealed acute interstitial nephritis drug-related and acute tubular injury. She was treated with prednisolone1 mg/kg with improved renal function.
Discussion
Acute renal injury, particularly acute interstitial nephritis, is not a recognized side effect of Belvarafenib.
This is the first reported case of a pan-RAF agent kidney adverse effects manifested by AIN and ATI. A literature review reported no renal adverse effects associated with pan-RAF agents.
Belvarafenib is a novel agent; further research and time are required to determine its adverse effects incidence. However, clinicians must remain vigilant about the potential kidney adverse effects of this agent and consider a kidney biopsy to assess AIN in patients whose AKI does not respond promptly to discontinuing Belvarafenib and supportive care.