Oncotarget: Rapid onset type 1 diabetes with anti-PD-1 directed therapy

Volume 11 , Issue 28 of Oncotarget features " Rapid onset type 1 diabetes with anti-PD-1 directed therapy ", by Yun et al. and reported that Type 1 diabetes is a rare immune-related adverse event caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis .

Of the patients who received immunotherapy, 5 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- 1 dose.

Four patients had new-onset diabetes with mean Hb A1c of 9.1% on DKA presentation and persistent elevations over time.

Two patients who tested positive for glutamic acid decarboxylase 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.

The case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence.

Dr. Sandip Pravin Patel from The Division of Hematology-Oncology in the Department of Medicine at The University of California San Diego said, " Cancer immunotherapy has broadened in clinical use over the last decade with FDA approval for treatment of various malignancies including melanoma , non-small cell lung cancer (NSCLC), renal cell carcinoma , urothelial carcinoma , head, and neck carcinomas , cutaneous squamous cell cancer , microsatellite unstable tumors , and Hodgkin's lymphoma . "

Autoimmune type 1 diabetes is generally associated with positive autoantibodies to islet proteins including glutamic acid decarboxylase, insulin, insulinoma-associated antigen-2, zinc transporter 8, and islet cells.

However, only a subset of patients who acquire type 1 diabetes is found to have autoantibodies and specific HLA alleles, making these biomarkers poor predictors of diabetes incidence.

Given the rarity of type 1 diabetes as an ir AE, the authors sought to characterize the real-world diagnosis, management, and sequelae of patients who developed this ir AE in the context of their immune checkpoint blockade.

This Oncotarget paper highlights the rapid kinetics of type 1 diabetes in patients on checkpoint inhibitors.

Type 1 diabetes presented as DKA for all patients in this series and all but one patient had a new diagnosis of diabetes, without antecedent laboratory or imaging findings.

The Patel Research Team concluded in their Oncotarget Research Paper that their case series illustrates the rare incidence of immunotherapy-induced type 1 diabetes and describes the rapid course of this disease in patients.

Regardless of whether or not patients remain on checkpoint inhibitors, those with immunotherapy-induced diabetes are at risk for hyperglycemia and recurrent DKA. Surveillance of glycemia or Hb A1c does not predict diabetes but does have a role after type 1 diabetes arises as glycemia fluctuates and elevated Hb A1c levels persist.

Furthermore, GAD antibodies are present in about half of patients who develop type 1 diabetes after immunotherapy, warranting additional investigations into whether this is all association and a marker of immune attack.

Given the absence of prescient laboratory or imaging findings in patients who develop type 1 diabetes on anti-PD-1 therapy, patients should be counseled on the symptoms of hyperglycemia which include polyuria, polydipsia, abdominal pain, nausea and emesis and seek medical attention immediately.

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DOI - https://doi.org/10.18632/oncotarget.27665

Full text - https://www.oncotarget.com/article/27665/text/

Correspondence to - Sandip Pravin Patel - patel@ucsd.edu

Keywords - type 1 diabetes , diabetic ketoacidosis (DKA) , immune-related adverse event (irAE) , immunotherapy , PD-1 inhibitors

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