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.

“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 –

[email protected]

Keywords

–


type 1 diabetes

,

diabetic ketoacidosis (DKA)

,

immune-related adverse event (irAE)

,

immunotherapy

,

PD-1 inhibitors

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