NIVOLUMAB-INDUCED DIABETIC KETOACIDOSIS

Abstract

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Immune checkpoint inhibitors such as nivolumab are used to treat a diverse spectrum of malignancies. There has been an increased percentage of patients eligible for the use of checkpoint inhibitors in cancer therapy over recent years. With the increased use of these medications, more immune-related adverse events (irAEs) have been identified and are becoming more common in clinical practice, raising the importance of early recognition. We present a case of a 62-year-old male with a history of non-insulin dependent diabetes mellitus type II who presented with diabetic ketoacidosis (DKA) after 2 cycles of nivolumab. CASE PRESENTATION: The patient is a 62-year-old male with a past medical history of stage III C melanoma, non-insulin dependent type 2 diabetes, and hypertension. He had been started on nivolumab for malignant melanoma and completed 2 cycles. Approximately 10 days after his second cycle, the patient developed progressive confusion, polydipsia, and weakness, and presented to the emergency room. On arrival the patient had lab abnormalities consistent with DKA including glucose 773 mg/dL, anion gap 34, HCO3 < 5 mmol/L, pH 7.071, and beta-hydroxybutyrate 135 mg/dL. The patient was admitted to the intensive care unit and started on an insulin drip, which was transitioned to subcutaneous insulin before discharge. The patient decided to stop nivolumab given the irAE. DISCUSSION: With the increased use of immune checkpoint inhibitors, physicians should be familiar with the common irAEs that have been reported, including in the gastrointestinal system (colitis, hepatitis, pancreatitis), endocrine system (DKA, type I diabetes, hypoparathyroidism), cardiovascular system (myocarditis, cardiac arrest, heart failure), pulmonary system (pneumonitis), and renal system (AKI). It has been shown in a small cohort study that DKA from nivolumab tends to occur within the first five cycles of therapy. In addition to causing DKA, nivolumab has also been shown to worsen glycemic control in patients with existing type II diabetes, leading to increased insulin requirements. Patients with a known history of diabetes who are starting nivolumab therapy should be made aware of this irAE in order to closely monitor for signs of hyperglycemia during the first few cycles of therapy. CONCLUSIONS: Checkpoint inhibitors are being more frequently used to treat certain types of malignancies. Practitioners should be aware of potentially serious complications including DKA and worsening glycemic control, such as reported with this patient. Monitoring blood glucose and HbA1C levels before and after initiation of an immune checkpoint inhibitor should be discussed with patients prior to initiating therapy, in order to help monitor for potentially serious complications, especially if the patient has diabetes. Reference #1: Bajwa R, Cheema A, Khan T, et al. Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study. J Clin Med Res. 2019;11(4):225-236. doi:10.14740/jocmr3750 Reference #2: Kotwal A, Haddox C, Block M, Kudva YC. Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes. BMJ Open Diabetes Res Care. 2019;7(1):e000591. Published 2019 Feb 13. doi:10.1136/bmjdrc-2018-000591 DISCLOSURES: No relevant relationships by Jonathan Burgei, source=Web Response