Recurrent hyperglycemic hyperosmolar state after re-administration of dose-reduced ceritinib, an anaplastic lymphoma kinase inhibitor

Abstract

Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor with clinical activity in crizotinib-resistant ALK-positive non-small cell lung cancer and in treatment-naïve ALK-positive disease. Hyperglycemia is a known adverse event, but the mechanism by which ceritinib causes hyperglycemia is unknown, and whether ceritinib causes hyperglycemic emergencies is unclear. Here, we report the case of a patient with a hyperglycemic hyperosmolar state (HHS) recurrence after the re-administration of dose-reduced ceritinib. A 78-year-old man with type 2 diabetes diagnosed as having advanced lung adenocarcinoma had been treated with alogliptin (25 mg/day) for the diabetes and with ceritinib for the lung cancer. After 28 days of ceritinib administration, he was admitted to our hospital due to HHS. His blood glucose level improved with insulin therapy after discontinuation of the ceritinib. He then received re-administration with a decreased ceritinib dose while maintaining the insulin treatment to control his blood glucose, but his HHS recurred. We discontinued the ceritinib for other side effects and noticed the HHS disappeared. Our findings suggest that ceritinib can cause HHS and that HHS may recur even after dose reductions.