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Abstract: TH-PO391

Is Diabetic Ketoacidosis Synonymous with Death in Patients on Enfortumab Vedotin for Urothelial Carcinoma?

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Atemnkeng, Francis Njukeng, Westchester Medical Center, Valhalla, New York, United States
  • Aguilar, Fatima, Westchester Medical Center, Valhalla, New York, United States
  • Chugh, Savneek S., Westchester Medical Center, Valhalla, New York, United States
  • Gupta, Sanjeev, Westchester Medical Center, Valhalla, New York, United States
  • Klein, Michael D., Westchester Medical Center, Valhalla, New York, United States
Introduction

Enfortumab vedotin (EV), is a novel breakthrough therapy which received accelerated FDA approval in 2019 for the treatment of metastatic urothelial carcinoma in patients who have failed other lines of treatment. The characteristics of its adverse effects especially diabetic ketoacidosis (DKA) are not well understood.

Case Description

A 57-year-old male with no history of diabetes, diagnosed with urothelial carcinoma two years prior, failed several lines of treatment including platinum-based chemotherapy and immune checkpoint inhibitors. He developed metastasis and was started on EV. After his second dose of EV, he was admitted to the ICU for diabetic ketoacidosis (DKA) with a high anion gap metabolic acidosis, serum bicarbonate of 12 mEq/L, blood Ph 7.2, hyperglycemia to 450 mg/dL, positive ketones in urine, an elevated C-peptide, with an initial hemoglobin A1C of 7.7%. He was in shock requiring multiple pressors and developed oliguric AKI (serum creatinine 1.5 mg/dL, baseline 0.7 mg/dL). He was intubated for airway protection and started on continuous renal replacement therapy. Despite aggressive treatment, the patient died on hospital day 2.

Discussion

EV is an antibody-drug conjugate which joins an antibody directed against the cell adhesion molecule, nectin-4, which is highly expressed in urothelial carcinoma, with monomethyl auristatin E, an inducer of cell cycle arrest and apoptosis. Just 2 cases of DKA due to EV have been reported since its approval for use in metastatic urothelial carcinoma (One at the 2020 American Thoracic Society Conference and the other at the 2021 American Society of Nephrology Conference). The precise mechanism for the development of DKA is yet unidentified. An elevated C-peptide, noted in one of the reported cases, suggests insulin resistance, but the very rapid progression of the acidosis and death within three days in all the cases suggests some other effects of the drug on glucose metabolism still to be elucidated. There is an FDA warning on its use in patients with glucose over 250 mg/dl, but this was insufficient to prevent DKA in the reported patients. Our patient had an elevated A1C on admission. Therefore, we strongly suggest screening for diabetes in every patient considered for EV, and to avoid it if A1C is greater than 7%.