J. Xiong, J. Li, Z. Wang, S. Lu, S. Liang, W. Xiao, Y. Han, et al. (2025). Case report: pembrolizumab-induced acute type 1 diabetes mellitus and diabetic ketoacidosis in a perioperative esophageal squamous cell carcinoma patient. AME case reports, 9, 61. https://doi.org/10.21037/acr-24-159

PubMed 40330922

[Abstract]
BACKGROUND: Immune checkpoint inhibitor (ICI) therapy rarely results in severe immune-related adverse events (irAEs). Autoimmune diabetes, an uncommon but serious irAE, can be life-threatening if not promptly treated. Although ICIs have been widely used in cancer therapy, there have been no reported cases in China of autoimmune diabetes developing during the perioperative treatment of esophageal squamous cell carcinoma (ESCC). This case report provides a significant clinical contribution by presenting the first documented instance of such an occurrence, emphasizing the need for vigilance and appropriate management strategies.

CASE DESCRIPTION: We present a 52-year-old male with locally advanced stage III locally advanced lower thoracic ESCC who developed type 1 diabetes mellitus (DM1) leading to diabetic ketoacidosis (DKA) after pembrolizumab treatment. The patient had no prior history of diabetes mellitus. He initially presented with progressive dysphagia and underwent two cycles of chemo-immunotherapy with albumin paclitaxel, carboplatin, and pembrolizumab as neoadjuvant therapy, followed by maintenance pembrolizumab after minimally invasive esophagectomy. Following the fifth course, he was admitted to the hospital in a comatose state and quickly diagnosed with DKA. Hemoglobin A1c (HbA1c) was 7.3%, and fasting C-peptide and insulin assays were significantly low. Detailed blood glucose levels and HbA1c were monitored before pembrolizumab initiation, and pre-treatment levels were normal. Pathological examination confirmed a moderately differentiated ESCC with no signs of metastatic disease. The patient received prompt multidisciplinary treatment and has been under follow-up for 10 months with no recurrence of ESCC but requiring ongoing management of diabetes.

CONCLUSIONS: In summary, this case highlights the rare but potentially life-threatening risk of autoimmune diabetes following pembrolizumab therapy in ESCC patients. The unique clinical contributions of this case include identifying the onset of DM1 during the perioperative period and emphasizing the importance of early detection of DKA symptoms. Clinicians should remain vigilant for such irAEs, ensuring regular monitoring of blood glucose and thyroid function in patients undergoing ICI therapy. Further research is needed to clarify the pathogenesis of pembrolizumab-induced diabetes and develop guidelines for monitoring and managing these adverse events in ESCC patients.