Diabetic Ketoacidosis Triggered by Pembrolizumab in a Patient with Bladder Cancer

Abstract

This is a 71-year-old male with history of Hypertension, well controlled type 2 DM on metformin (HbA1c 6.6%), and high grade urothelial bladder cancer treated with transurethral resection of the bladder. Due to cancer progression, he required neoadjuvant chemotherapy followed by Pembrolizumab in July 2017. He presented with fatigue, polyuria and polydipsia in August 2017. He was diagnosed with DKA and managed in the ICU. Workup revealed HbA1c 9%, high GAD-65 antibody (>250 IU/ML), and low C-peptide (0.26 ng/ml). He was stabilized and discharged on insulin. T cell activity is regulated by programmed death ligand-1(PD-L1)/programmed death-1 (PD-1). Tumor cells select specific immune-checkpoint pathways as a mechanism of immune resistance against T cells and evade the antitumor immune response by overexpressing PD-L1. Pembrolizumab is a humanized monoclonal antibody against PD-1 acting as an immune checkpoint inhibitor (ICI). Pembrolizumab is approved for treating metastatic urothelial carcinoma, cisplatin-ineligible cancer or disease progression after cisplatin therapy. ICIs are associated with multi-system immune related adverse events (irAEs) due to the disinhibition of the host immune homeostasis. Most of the irAEs are reversible with supportive treatment, however life-threatening irAEs can occur including severe skin reaction, type 1 DM, hypophysitis, and rhabdomyolysis. In our patient, we suspected pembrolizumab was related to new onset type 1 DM. type 1 DM and DKA were reported in 6 (0.2%) of 2,799 patients on Pembrolizumab in 3 randomized, open-label, and active-controlled clinical trials. There are 12 reported cases of PD-1/PD-L1-associated type 1 DM. The onset of disease from use varied from 1 week to 12 months, with most patients presenting with type 1 DM with DKA. ICIs are breakthroughs in cancer treatment. Clinicians should be aware of their possible irAEs. The development of autoimmune diabetes is rare, but its complications are life threatening if not attended to immediately. Disclosure T. Al Shamy: None. M. Aguasvivas: None. M. Serhan: None. M.M. Fojas: None.