LBSUN292 Learning Lesson From A Case of Fulminant Type 1 Diabetes Mellitus Shortly After Pembrolizumab Treatment

Abstract

Abstract Background Immune checkpoint inhibitors (ICIs) in cancer treatment are considered one of the major breakthroughs in the past decade. Pembrolizumab (PBL) is one of the immune checkpoint inhibitors that targets the programmed cell death protein-1 (PD-1) receptor in order to block its interaction with programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2). By inhibition of these molecules, PBL helps increase T-cell activation against cancer cells. Unfortunately, this inhibition also enhances autoimmunity against normal cells, leading to immune-related adverse events (irAEs) including endocrinopathies. Unlike other irAEs, endocrinopathies are usually irreversible upon diagnosis. While hypophysitis, hypo/hyperthyroidism, and adrenal insufficiency are more commonly reported, type 1 diabetes mellitus (T1DM) is also seen around 0.9 to 1.9% of cases. Unfortunately, it can become fatal if not being promptly recognized. To raise awareness about this life-threatening adverse event, we are reporting a case of new onset T1DM, presenting with diabetic ketoacidosis (DKA) only after 22 days of the first PBL infusion. Clinical case A 19-year-old male was recently diagnosed with NUT (nuclear protein in testis) carcinoma of the left floor of mouth with high PD-L1 score. NUT carcinoma is a rare type of squamous cell cancer with chromosomal rearrangement in the nuclear protein in testis gene (NUTM1) that makes the cancer aggressive and resistant to standard therapy, hence requiring a multimodal approach. This patient underwent surgery followed by concurrent cisplatin-radiation and PBL. Two weeks after his first PBL infusion, he suddenly developed polydipsia, polyuria, and nausea. He continued to receive the second PBL dose on day 20 and developed DKA on day 21. His work-up revealed a plasma glucose of 856 mg/dL, anion gap of 20 (H), CO2 of 17 mEq/L (L), and beta-hydroxybutyrate of 3.35 mmol/L (H), while hemoglobin A1C of only 5.5% suggesting his fulminant progression. He was immediately treated with DKA protocol with clinical improvement. The patient was discharged on basal bolus insulin regimen. He had non-detectable C-peptide (<0.10 ng/mL) and high GAD Antibody (>250 IU/mL) levels, which was consistent with PBL induced T1DM. Conclusion PBL use has been linked to multiple endocrinopathies and even though rare, DKA can also be seen in setting of T-cell mediated irreversible damage to pancreas beta cells. Due to life threatening potential of DKA, clinicians should monitor patients receiving immune checkpoint inhibitors closely and should be aware symptoms of hyperglycemia for earlier intervention. | Keywords: pembrolizumab, NUT carcinoma, diabetic ketoacidosis Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.