PEMBROLIZUMAB-INDUCED TYPE 1 DIABETES PRESENTING AS DIABETIC KETOACIDOSIS

Abstract

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor, a humanized monoclonal IgG4 antibody against programed death 1 (PD-1). It is approved for treatment of malignancies including but not limited to, metastatic melanoma, non-small cell lung, renal cell, squamous cell, gastric, colon, cervical and urothelial carcinomas as well as classic Hodgkin lymphoma.[1] Immune check point inhibitors are rarely associated with immune adverse events. Endocrinopathies such as hypo and hyperthyroidism are more common compared to hypophysitis, type 1 diabetes mellitus (T1DM) and adrenal insufficiency.[2] We present a case of pembrolizumab induced severe DKA. CASE PRESENTATION: A 67-year-old female with history of recurrent esophageal squamous cell cancer despite concurrent chemoradiation and esophagectomy, previously treated with carboplatin paclitaxel and FOLFOX, now on immunotherapy with pembrolizumab (second cycle given two weeks prior), presented to a community hospital with malaise, nausea and emesis. Investigations revealed blood glucose of 595 with anion gap of 30. Urinalysis showed 3+ glucose and 2+ ketones, beta hydroxybutyrate 6.1, pH of 7.19 with base deficit 16.4. Patient was admitted to the intensive care unit with the diagnosis of moderate diabetic ketoacidosis (DKA) without evidence of infection. Patient was treated with institutional DKA protocol and later transitioned to basal-bolus insulin regimen. Studies during hospitalization revealed hemoglobin A1c (HbA1c) of 7.9%. Glutamic acid decarboxylase 65 antibody was elevated at 0.81 and C peptide was low at 0.1. In the absence of preexisting diabetes, these findings were consistent with pembrolizumab-induced autoimmune-mediated T1DM precipitating DKA. DISCUSSION: Pembrolizumab is associated with endocrinopathies with hyperglycemia reported around 45%, grade 3-4 hyperglycemia in 3-6% and T1DM or DKA only in 0.1 % individuals.[3] With increasing reports about pembrolizumab associated DKA, we suggest that the patients on pembrolizumab need to be educated about possible symptoms of diabetes and DKA. Other than autoimmune T1DM development, common side effects of treatment including decreased appetite, diarrhea and nausea may also contribute to starvation ketosis. Baseline HbA1c and interval blood glucose measurements may help in timely identification of individuals at risk of development of T1DM and prevention of DKA, which is a common initial presentation. European society for medical oncology (ESMO) recommends regular glucose monitoring in immune checkpoint inhibitors.[2] CONCLUSIONS: Endocrinopathies including life-threatening DKA may result with pembrolizumab use. Measurement of baseline HbA1c and regular monitoring of blood glucose in these patients may help identify patients at risk for pembrolizumab associated T1DM and DKA. Reference #1: Joshi, S.S., S.B. Maron, and D.V. Catenacci, Pembrolizumab for treatment of advanced gastric and gastroesophageal junction adenocarcinoma. Future Oncol, 2018. 14(5): p. 417-430. Reference #2: Hakami, O.A., et al., A case of pembrolizumab-induced severe DKA and hypothyroidism in a patient with metastatic melanoma. Endocrinol Diabetes Metab Case Rep, 2019. 2019. Reference #3: Hwangbo, Y. and E.K. Lee, Acute Hyperglycemia Associated with Anti-Cancer Medication. Endocrinol Metab (Seoul), 2017. 32(1): p. 23-29. DISCLOSURES: No relevant relationships by Allisa ALpert, source=Web Response No relevant relationships by Christine Blaski, source=Web Response No relevant relationships by Adam Matos, source=Web Response No relevant relationships by Jose Mena, source=Web Response No relevant relationships by Ian Nagus, source=Web Response No relevant relationships by Tatyana Sycheva, source=Admin input No relevant relationships by Usama Talib, source=Web Response