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

JCEM case reports Pub Date : 2024-11-25 eCollection Date: 2024-12-01 DOI:10.1210/jcemcr/luae212

Rachel Hovelroud, Sarah Goh Xiu Ming, Donald S A McLeod, Peter J Donovan, Gary Ng, Maree Mungomery

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Abstract

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.

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一例非糖尿病女性因严重胰岛素抵抗而发生恩福单抗维多汀相关性糖尿病酮症酸中毒的病例

恩福单抗维多汀是一种新型抗体药物共轭物（ADC），已被批准用于治疗尿路上皮癌。一种极少报道的不良反应是由胰岛素抵抗引起的危及生命的糖尿病酮症酸中毒（DKA）。我们报告了一例患有转移性尿路癌的 62 岁非糖尿病女性患者，她在第三次服用恩福单抗维多汀后出现了 DKA，胰岛素需求量极大，每天超过 1000 单位，入院第 7 天时胰岛素需求量完全消失。包括该病例在内，在已报道的 9 例恩福单抗维多汀相关性 DKA 患者中，有 3 例患者存活了下来。恩福单抗维多汀的细胞毒性成分单甲基乌司他丁 E (MMAE)很可能是导致该病的原因，但其确切机制仍不清楚。这一罕见的临床事件对胰岛素输注的常规方案和实践提出了挑战，本病例提供的证据有助于理解恩福单抗维多汀导致酮症酸中毒的机制。

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JCEM case reports

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