Rapid onset type 1 diabetes with anti-PD-1 directed therapy
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Karen Yun1, Gregory Daniels2, Kathryn Gold2, Karen Mccowen3 and Sandip Pravin Patel2
1 Department of Medicine, University of California San Diego, San Diego, CA 92103, USA
2 Division of Hematology-Oncology in the Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA
3 Division of Endocrinology in the Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA
|Sandip Pravin Patel,||email:||[email protected]|
Keywords: type 1 diabetes; diabetic ketoacidosis (DKA); immune-related adverse event (irAE); immunotherapy; PD-1 inhibitors
Received: May 01, 2020 Accepted: June 15, 2020 Published: July 14, 2020
Type 1 diabetes is a rare immune-related adverse event (irAE) caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis (DKA). Using our electronic medical record, we identified 1327 adult patients who received PD-(L)1 or CTLA-4 inhibitors from 2013 to 2018. Of the patients who received immunotherapy, 5 (0.38%) patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD-(L)1 dose. All patients were treated with anti-PD-1 therapy (nivolumab or pembrolizumab). Four patients had new onset diabetes with mean HbA1c of 9.1% on DKA presentation and persistent elevations over time. Two patients who tested positive for glutamic acid decarboxylase (GAD) antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later. Type 1 diabetes occurs within a wide time frame after anti-PD-1 initiation and commences with an abrupt course. Our case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence. GAD autoantibodies could portend earlier onset for diabetes, although further prospective studies are needed to elucidate their diagnostic utility and contribution in therapeutic interception.
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