Endocrine side effects of cancer immunotherapy

Abstract

Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies.

Thyroiditis and immune check point inhibitors: the post‐marketing experience using the French National Pharmacovigilance database

“…In our series, ICI treatment was continued for more than half of the patients, as ICI efficacy was good and thyroiditis controlled in all of them. Considering the available algorithms about the management of ICI‐induced thyroiditis and the result of our study, we propose a more precautious management of thyrotoxicosis (adapted from Cooper ) avoiding antithyroid agents in patients with thyrotoxicosis when possible, delaying levothyroxine supplementation in asymptomatic patients with hypothyroidism, and encouraging continuation of immunotherapy in patients with controllable thyroiditis, even severe ( Figure ).…”

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

“…Cases in which ICI treatment leads to diabetic ketoacidosis are even less frequent. The median time to the onset of T1DM is reported to be 4.4 months; however, the time to onset ranges from 7 days to 12 months in reported cases . Thus, it is difficult to predict the timing of the onset of T1DM.…”

“…Various irAEs are well known to occur in patients undergoing ICI therapy. T1DM is a relatively rare irAE, accounting for only 0.9% by nivolumab and 0.2% by pembrolizumab . Cases in which ICI treatment leads to diabetic ketoacidosis are even less frequent.…”

“…ICI therapy induces various immune‐related adverse effects (irAE), including type 1 diabetes mellitus (T1DM), which is relatively infrequent but difficult to treat . Several case reports on the occurrence of T1DM as an irAE in melanoma and NSCLC patients have been published.…”

Rapid onset type 1 diabetes associated with the programmed cell death‐1 inhibitor pembrolizumab

“…Programmed cell death 1 (PD‐1) inhibitors have improved survival in some metastatic cancers but are associated with autoimmune side‐effects . The association of fulminant onset type 1 diabetes with the use of PD‐1 inhibitors for malignancy was first recognised in 2015.…”