Diabetic Ketoacidosis as an Initial Presentation of Anti-PD-L1 Antibody Durvalumab-Induced Diabetes Mellitus

Le résumé fourni par la source

A 71 year old female with a history of hypothyroidism and non-small cell adenocarcinoma of the lung on immunotherapy with durvalumab presented with two days of nausea, vomiting, and generalized malaise.Review of systems was positive for new-onset polyuria and polydipsia.She received durvalumab five days prior to presentation.Initial vital signs were unremarkable.Physical examination was significant for decreased skin turgor and dry mucous membranes.Laboratory studies revealed a leukocytosis of 18.7, as well as significant metabolic abnormalities, including sodium of 124mEq/L, potassium of 5.2mEq/L, chloride of 83mEq/L, bicarbonate of 16mEq/L, creatinine of 2.14mg/dL, and most significantly, blood glucose of 1,150g/dL.Anion gap was 25.A venous blood gas demonstrated metabolic acidosis with a pH of 7.21, pCO2 40, and bicarbonate of 15.She had no history of hyperglycemia.She was diagnosed with diabetic ketoacidosis and was admitted to the intensive care unit for administration of IV normal saline and a continuous insulin infusion.Further workup demonstrated the presence of both urine and serum ketones.HbA1c was mildly elevated at 6.9%.Anti-GAD 65 antibodies were found to be positive at greater than 25,000 U/mL and c-peptide level was low at 0.2ng/mL, a pattern consistent with type I diabetes mellitus.Her anion gap closed within six hours and she was transitioned to a basal-bolus insulin regimen with plans for outpatient endocrinology follow up.Durvalumab is a programmed death-ligand 1 (PD-L1) inhibitor approved for the treatment of stage III non-resectable non-small cell lung cancer.The first trial examining the use of durvalumab for non-small cell lung cancer noted significant adverse endocrine events with durvalumab use, however, the majority of these were related to thyroid function.Only one out of the 1,414 patients in the trial developed new-onset on type 1 diabetes mellitus (<0.001%).Since that trial, there have been only three published case reports of new-onset antibody positive type 1 diabetes mellitus connected to durvalumab use.The patient discussed here presented in diabetic ketoacidosis with a blood glucose above 1,100, low C-peptide, and positive anti-GAD 65 antibodies.The rapid progression of her clinical course, as well as the relative rarity of durvalumab-induced type 1 diabetes mellitus in the literature make this case a notable one.Immune checkpoints remain a promising target for pharmacologic agents in treating oncologic conditions, however science has yet to fully elucidate the potential adverse effects of these medications.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.