A Case of Enfortumab Vedotin-Associated Diabetic Ketoacidosis With Severe Insulin Resistance in a Nondiabetic Woman

Enfortumab vedotin is a novel antibody-drug conjugate (ADC) approved to treat urothelial carcinoma. One rarely reported adverse effect has been life-threatening diabetic ketoacidosis (DKA) driven by profound insulin resistance. We report a case of a 62-year-old nondiabetic woman with metastatic urothelial carcinoma who experienced DKA following her third dose of enfortumab vedotin, with extreme insulin requirements of > 1000 units daily, and full resolution of insulin requirement by day 7 of admission. Including this case, 3 of 9 reported patients with enfortumab vedotin-associated DKA have survived. Monomethyl auristatin E (MMAE), the cytotoxic component of enfortumab vedotin, is the likely cause, although the exact mechanism remains unclear. This rare clinical event challenges the usual protocols and practice surrounding insulin infusion administration, and this case provides evidence to assist in understanding the mechanism by which enfortumab vedotin causes ketoacidosis.