Abstract: PO1881
AKI with BRAF and MEK Inhibitors May Not Be a Class Effect
Session Information
- Cancer and Kidney Diseases: Nephrotoxins, RCC, and More
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Gerardine, Supriya, Weill Cornell Medicine, New York, New York, United States
- Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States
- Glezerman, Ilya, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Introduction
BRAF tyrosine kinase inhibitors are used in the treatment of BRAF mutant metastatic melanoma. Simultaneous MEK inhibition has been shown to have better response rates and fewer side effects. Renal toxicity has been reported with these agents which can include AIN, ATN and Fanconi syndrome. We report a case of AKI due to biopsy proven AIN from BRAF and MEK inhibitor vemurafenib and cobimetinib
Case Description
This is a 64-year-old woman with diabetes mellitus type 2, stage IV melanoma with BRAF V600E mutation and baseline serum creatinine (SCr) of 0.8 (0.6-1.1) mg/dL. She has been treated with multiple chemotherapy regimens and immunotherapy (last dose of immunotherapy 28 months prior to presentation). Patient received reduced dose dabrafenib and trametinib until 8 months prior to presentation but stopped due to development of fever and AKI (SCr 1.7mg/dL). She was started on vemurafenib 480 mg BID every other day and cobimetinib 40mg every other day 6 ½ months before presentation. Two months later the vemurafenib dose was increased to 960mg BID but patient was noted to have AKI with SCr of 4.5 mg/dl and vemurafenib and cobimetinib were stopped. Her blood pressure was elevated to 154/70 mmHg. Urinalysis showed protein of 100 mg/dL, 0-3 RBC/HPF and 0-6 WBC/HPF. SCr improved to 2.2 mg/dL but remained elevated and renal consult was obtained with subsequent kidney biopsy. It showed active, subacute, and chronic interstitial nephritis with extensive tubular atrophy. Patient was treated with prednisone 50 mg daily and was tapered down to 10 mg daily over two months. Repeat CT scan showed new peritoneal nodules and she was started on a new BRAF/ MEK combination of encorafenib and binimetinib . She is currently tolerating these medications with SCr stable at 1.5mg/dl.
Discussion
BRAF and MEK inhibitors are associated with AKI secondary to ATN and AIN. In the above case, the patient developed AIN with vemurafenib and cobimetinib which were discontinued resulting in significant improvement in kidney function. Due to progression of disease she was started on encorafenib and binimetinib which she is tolerating well. This case demonstrates that renal toxicity from BRAF and MEK inhibitor may not be a class effect and may also be dose dependent. It may be possible to consider a dose reduction or switch to another medication in the same class if renal toxicity is noted.