Abstract: PO1874
Proximal Tubule Dysfunction and Hemophagocytic Lymphohistiocytosis (HLH) Following Use of Novel Immune Checkpoint Inhibitor
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
- Cook, David L., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
- Watson, Maura A., Walter Reed National Military Medical Center, Bethesda, Maryland, United States
Introduction
Bintrafusp alfa is a bifunctional fusion protein that inhibits transforming growth factor β (TGF-β) and programmed death ligand 1 (PD-L1) currently being studied for treatment of various cancers. Reported adverse effects include rash and hypothyroidism. We present a patient with renal proximal tubule dysfunction manifested by multiple electrolyte derangements after receiving bintrafusp alfa.
Case Description
A 62 year-old male with squamous cell carcinoma of the head and neck refractory to chemotherapy, radiation and proton therapy was admitted for dysphagia, fever and hypotension two weeks after starting experimental immunotherapy with bintrafusp, NHS/IL-12, and PDS101. He developed hypokalemia requiring high dose supplementation, hypophosphatemia, hyponatremia, hypocalcemia, hypoalbuminemia and non-nephrotic range proteinuria. Other labs showed pancytopenia, elevated transaminases, thyroid stimulating hormone, inflammatory markers and anti-glomerular basement membrane antibodies. Work up showed renal potassium, phosphorus and sodium wasting with glomerular filtration rate (GFR) above 75 mL/min. Respiratory distress and hemoptysis concerning for diffuse alveolar hemorrhage led to ICU transfer. Kidney biopsy showed no glomerular injury, linear basement membrane fluorescence, glomerulosclerosis, interstitial fibrosis or immune complex-deposits. Proximal tubules were focally dilated, suggestive of tubular injury. HLH was subsequently diagnosed and treatment with steroids and intravenous immune globulin was followed by electrolyte normalization and improved clinical status.
Discussion
Immune checkpoint inhibitors are increasingly used for cancer treatment. These medications carry risk of immune-related adverse effects. While secondary HLH has been reported with use of immune checkpoint inhibitors, cases are few and renal involvement even rarer. To date there have been no documented cases of secondary HLH with profound electrolyte derangements but normal GFR after receiving bintrafusp alfa. Awareness of these adverse events is necessary as these medications see more widespread use.
The views expressed are those of the authors and do not necessarily reflect the official policy the Department of Defense or the U.S. government.