Fulminant Type 1 Diabetes Mellitus Caused by Long-Term Nivolumab Administration Followed by Nivolumab plus Cabozantinib Combination

Abstract

Nivolumab, an immune checkpoint inhibitor (ICI), is now used to treat many advanced cancers, including non-small cell lung cancer (NSCLC) and renal cancer. Immune-related adverse events are characteristic side effects of ICIs. Among them, fulminant type 1 diabetes mellitus is an infrequent but potentially life-threatening and clinically significant concern. Cabozantinib is known as a multikinase inhibitor. In recent years, combination therapy with nivolumab and cabozantinib has begun to be used to treat renal cell carcinoma. A 74-year-old man with no history of diabetes was treated with nivolumab for 5 years for NSCLC, followed by the combination of nivolumab and cabozantinib for clear cell renal cell carcinoma. He was diagnosed with fulminant type 1 diabetes 5 weeks after starting combination therapy, with symptoms of nausea and dry mouth. He was admitted to the intensive care unit and improved clinically with continuous insulin infusion and saline. The involvement of cabozantinib in the development of fulminant type 1 diabetes with long-term nivolumab use, which has not been reported previously, is unknown, but caution may be necessary in terms of glycemic control in combination therapy with nivolumab and cabozantinib.