Severe Hypoglycemia Caused by Lenalidomide

Lenalidomide is commonly used for multiple myeloma as either induction or maintenance therapy. The agent is associated with a host of adverse effects, but hypoglycemia has only been reported in one phase I trial in patients with solid tumors. We describe a 74-year-old woman who experienced grade 3 hypoglycemia (blood glucose level 35 mg/dl) likely related to lenalidomide. Her medical history was significant for refractory myeloma and type 2 diabetes mellitus. Lenalidomide was started as maintenance therapy following autologous bone marrow transplantation. Approximately 3 years later, she developed refractory hypoglycemia necessitating hospital admission despite stopping antihyperglycemic agents 4 weeks prior to admission. Lenalidomide was withheld during her admission and restarted 2 days prior to discharge. Work-up for causes of persistent hypoglycemia was negative, and her glucose levels improved over her 26-day hospitalization. She was readmitted approximately one month later for hypoglycemia, and lenalidomide was permanently discontinued. Again, work-up for causes of hypoglycemia was negative, and her glucose levels stabilized over her hospitalization. After discontinuation of lenalidomide, hypoglycemia did not recur, and within 1 year the patient required reinitiation of antihyperglycemic medications to control her glucose levels. Given the resolution of hypoglycemia with lenalidomide discontinuation and return of hyperglycemia after restarting the agent, it is likely that lenalidomide was the cause of the patient's hypoglycemia. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 9) between the patient's development of grade 3 hypoglycemia and lenalidomide therapy. Although this adverse drug reaction had been previously reported with lenalidomide during phase I trials in patients with solid tumors, only grade 1 or 2 hypoglycemia was reported in three patients. To our knowledge, this is the first reported case of grade 3 hypoglycemia caused by lenalidomide.