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Diabetes/Prediabetes/Hypoglycemia

(18.13) Refractory Diabetic Ketoacidosis From Tisotumab Vedotin-tftv, A Novel Antibody-Drug Conjugate

Saturday, May 11, 2024
9:15 AM – 9:30 AM CDT
Location: ePoster Showcase, Empire Ballroom Foyer, Level 2
Introduction : Antibody-drug conjugates (ADCs) are a novel oncologic therapeutic class that can target the effects of cytotoxic agents via phagocytosis and intracellular proteolysis. Vedotin is a microtubule disruptor used in multiple conjugations which have been reported to cause severe hyperglycemia and diabetic ketoacidosis (DKA) despite high-dose insulin therapy. This is the first case report of a refractory DKA due to the ADC tisotumab vedotin-tftv (TIVDAK).

Case(s) Description : A 45 year-old female with a history of severe obesity and type 2 diabetes was diagnosed with metastatic cervical cancer. Her diabetes was diet-controlled aside from a period of insulin therapy for glucocorticoid-induced hyperglycemia during chemotherapy treatment. After disease progression through multiple courses of chemotherapy and immunotherapy, she started tisotumab vedotin-tftv. She was admitted the following day for inferior vena cava obstruction from her tumor burden. Despite normal glucoses upon admission, she subsequently developed hyperglycemia to the 400s approximately 4 days after the dose of tisotumab vedotin-tftv. Despite escalating doses of subcutaneous insulin, she subsequently met criteria for DKA and transitioned to intravenous insulin therapy. Despite continuous infusion rates over 20 units/hour, she had persistent hyperglycemia over 250 mg/dl (65-99 mg/dL) and an anion gap over 20 mmol/L (7-16 mmol/L). Fifteen days after the dose of tisotumab vedotin-tftv, her hyperglycemia slowly improved and she was transitioned to U-500 insulin. Her insulin regimen was gradually decreased and eventually switched to basal-bolus until cessation 21 days after administration of tisotumab vedotin-tftv. She subsequently received a second dose without any significant hyperglycemia.

Discussion :

Severe hyperglycemia and refractory DKA are an increasingly documented side effect of ADCs containing vedotin. Our case is the first report of repeat ADC treatment following an episode of DKA. The mechanism of this dysfunction is not yet understood. As occurrences seem unpredictable, it may be prudent to counsel patients preemptively if they have existing insulin resistance. Further studies are needed to elucidate which patients are at greatest risk.