Abstract: SA-PO271
PR3 Positive Crescentic Glomerulonephritis in Pembrolizumab Treated Metastatic Melanoma
Session Information
- Trainee Case Reports - VI
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Thomas, Maria Joana Angeles, University of California Davis Medical Center, Sacramento, California, United States
- Chin, Andrew I., University of California Davis, Sacramento, California, United States
Introduction
Immune checkpoint blockade has demonstrated to be effective for treating various cancers including melanomas. Pembrolizumab, a monoclonal antibody that targets the programmed cell death (PD-1) receptor of lymphocytes, enhances immunologic destruction of cancer cells. The PD-1 pathway plays an important role in immunologic homeostasis, enabling the body to defend against pathogens while protecting against self-reactivity. Use of these medications may lead to dysregulation of T cell activation, causing a pathologic immune response, including inciting autoimmunity.
Case Description
A 73 year old woman with metastatic melanoma with normal renal function was treated with 4 doses of Pembrolizumab. Creatinine rose to 1.7 mg/dL. Biopsy revealed acute and chronic interstitial nephritis. After the drug was held, Prednisone 60 mg daily was started. Creatinine remained at 1.6 - 1.9 mg/dL. Twelve months later, she developed arthralgias and targetoid lesions on her fingers. A skin punch biopsy showed vasculitis. Creatinine was 5.2 mg/dL. UPC was 2.9 g/g. Complements were normal. Cryoglobulin, MPO, HIV, hepatitis panel and renal ultrasound were negative. She tested positive for PR3-ANCA at 1675 U/mL (normal 0-19 U/mL). Biopsy revealed pauci-immune crescentic glomerulonephritis (GN). She received 6 sessions of plasmapheresis, weekly Rituximab with Methylprednisolone, and later switched to Prednisone 60 mg daily. Creatinine improved with a decrease in PR3 titers. Rituximab maintenance infusions were terminated due to progression of melanoma.
Discussion
There are a few cases of Minimal Change Disease and IgA Nephropathy reported with PD-1 inhibitor, and a case of Granulomatous Polyangiitis after a single dose of Pembrolizumab. Immune-related adverse events have been cited to start within a few weeks to months after treatment, but can occur anytime after treatment discontinuation, with skin events usually the first to appear. Our patient presented with skin findings and had severe renal injury from PR3-positive GN. T-cell activation has been implicated in the development of crescentic GN. We postulate that Pembrolizumab set the scene for a dysregulation of T cell function, with development of a pathogenic autoantibody such as PR3-ANCA, as well as possibly unmasking an underlying autoimmunity. This report highlights an important potential renal effect from this drug.