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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

Category: Onconephrology

  • 1700 Onconephrology


  • 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

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.


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.