Glucocorticoids did not reverse type 1 diabetes mellitus secondary to pembrolizumab in a patient with metastatic melanoma

Abstract

Immune checkpoint inhibitors offer patients with advanced melanoma substantial improvements in survival. Unlike chemotherapy, immune checkpoint inhibitors such as ipilimumab and pembrolizumab cause unique immune-related adverse events (irAEs), including the development of endocrinopathies. We report a case of a man aged 60 years who developed diabetic ketoacidosis (DKA) following the use of pembrolizumab for the treatment of metastatic melanoma. He received four cycles of ipilimumab, before proceeding to pembrolizumab. Five weeks after initiating pembrolizumab, he presented in DKA with a pH of 7.0, bicarbonate of 7 mmol/L, blood glucose of 27 mmol/L and serum ketones of 5.9 mmol/L. Antibodies to glutamic acid decarboxylase (anti-GAD) and Islet antigen 2 (IA-2) were negative and C-peptide was low at 57 pmol/L (300-2350 pmol/L). There was no personal or family history of autoimmune conditions. Standard immunosuppression for irAEs was started using prednisolone in an attempt to salvage β cell function but was unsuccessful. To the best of our knowledge, this is the first reported attempt at reversing pembrolizumab-induced type 1 diabetes using glucocorticoids.

Continued administration of pembrolizumab for adenocarcinoma of the lung after the onset of fulminant type 1 diabetes mellitus as an immune‐related adverse effect: A case report

“…In this case, the diagnosis itself was relatively easy, and we could manage the acute phase of fulminant T1DM and ketoacidosis with sufficient fluid supply, electrolyte correction, and the administration of insulin. Generally, many irAEs can be managed by discontinuing the ICIs or with the use of steroids; these treatments rarely improve endocrine function in cases of hypothyroidism or T1DM . In this case, we did not use steroids as it was irreversible and the condition was manageable with insulin therapy.…”

“…Generally, many irAEs can be managed by discontinuing the ICIs or with the use of steroids; these treatments rarely improve endocrine function in cases of hypothyroidism or T1DM. 8,9 In this case, we did not use steroids as it was irreversible and the condition was manageable with insulin therapy.…”

Endocrine sequelae of immune checkpoint inhibitors

“…The use of glucocorticoids was not able to reverse T1DM in a patient treated with pembrolizumab for metastatic melanoma. 45 The proposed mechanism for the development of T1DM is that lower PD-1 expressing CD4+ cells may lead to activation of autoreactive T cells that can infiltrate pancreatic islet cells and ultimately lead to T1DM. 41 It is suspected that high-risk HLA class I and II genotypes may be associated.…”

Diabetes associated with immune checkpoint inhibition: presentation and management challenges

“…The incidence of immunotherapy‐induced Type 1 diabetes is reported to be ~0.4% ; however, reports suggest that the real‐world incidence may be significantly higher . Cohort studies of islet antibody‐positive people (mainly first‐degree relatives of people with Type 1 diabetes) have found that ~10% with a single positive antibody will progress to Type 1 diabetes .…”