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Abstract: FR-PO273

Acute Interstitial Nephritis and Its Recurrence due to BRAF-MEK Inhibitors for Melanoma

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Khan, Zahraa, 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

The efficacy of BRAF – MEK inhibitor therapy on survival in advanced melanoma has resulted in its widespread use. We describe two cases of biopsy proven Acute Interstitial Nephritis from BRAF-MEK inhibitors.

Case Description

Case One
51 year-old with melanoma, on binimetinib and encorafenib for two years developed acute kidney injury with creatinine of 2 mg/dL from baseline of 0.76 mg/dL two weeks ago. Labs revealed leukocytosis to 17,ooo, urinalysis with 41 WBC, 3 RBC, urine protein-creatinine 1.5 g/g, urine albumin-creatinine 44 mg/g and a negative urine culture. Encorafenib and binimetinib were held. Other work up revealed total protein 7 g/dL, elevated globulin 4.9 mg/dL 1, ANA 1:640, anti-dsDNA 1:80, anti-RF 23 IU/mL. Kidney biopsy revealed AIN. Prednisone was initiated at 1mg/kg/day, with return of baseline kidney function in four weeks, at which time prednisone was tapered off. She is undergoing surveillance monitoring for melanoma off BRAF-MEK inhibitors, with plan to switch to alternative drug within the class should there be recurrence of disease.
Case Two
64-year-old with metastatic melanoma on vemurafenib and cobimetinib for six months developed AKI with creatinine of 4 mg/dL from baseline of 1.2 mg/dL. Kidney biopsy revealed AIN. She was treated with prednisone 1 mg/kg/day and switched to encorafenib and binimetinib. Two months later, she developed another AKI, presumably AIN and steroids were prescribed. She was switched to immunotherapy, however due to progression of melanoma dabrafenib and trametinib was initiated, this time with prophylactic low dose prednisone at 10 mg daily. Her kidney function is improved with creatinine of 2 mg/dL and CKD stage 4.

Discussion

We report the first case series of AIN after BRAF-MEK inhibitors for advanced melanoma. We describe our approach to therapy which includes initial treatment with steroids to suppress the immune response, followed by switch to alternative drug, possibly within the same class. However, as described in case two, our patient developed an immune reaction to the second agent as well suggesting that the reaction is likely a class effect. This was offset by prophylactic low dose of steroids given at the time of re-initiating treatment with a BRAF-MEK inhibitor.