Autoimmune Polyendocrinopathy Induced by an Antibody (KN046) That Simultaneously Inhibits PD-L1 and CTLA-4: A Case Report and Literature Review

Abstract

Endocrine adverse reactions are one of the most common adverse reactions in the treatment of immune checkpoint inhibitors (ICIs), mainly involving the pituitary gland, pancreas, thyroid gland, adrenal gland and other glands, resulting in corresponding endocrine dysfunction. We report a 45-year-old man with non-small-cell lung cancer who developed hypophysitis 11 months after initiation of treatment with an anti-PD-L1/CTLA-4 bispecific antibody (KN046) that blocks both programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), followed by regular oral replacement doses of prednisone and levothyroxine tablets. The patient was diagnosed with type 1 diabetes mellitus (T1DM) with diabetic ketoacidosis (DKA) 25 months after the start of immunotherapy, presenting with acute hyperglycemic symptoms, ketoacidosis, and negative diabetic autoantibodies. By describing a case of KN046 immunotherapy involving multiple endocrine glands and reviewing relevant literature, we were able to summarize the clinical characteristics of KN046 immunotherapy-induced endocrine system-related immune-related adverse events (irAEs) for use in early detection, diagnosis and treatment.

Isolated adrenocorticotropic hormone deficiency following immune checkpoint inhibitors treatment often occurred in polyglandular endocrinopathies

“…Previous studies have largely focused on the incidence of single endocrine irAEs; however, people with one autoimmune disease are more likely to develop a second autoimmune disease [27]. Growing evidence suggested that polyendocrinopathy is common following ICI treatment, similarly to autoimmune endocrine diseases in general.…”

Case Report: Keratoacanthoma and type I diabetes secondary to treatment with PM8001, a bifunctional fusion protein targeting TGF-β and PD-L1

“…However, it is difficult to predict the occurrence of diabetes mellitus even with regular monitoring of the blood glucose changes. In general, this is indicated when insulin and C-peptide levels fall below one-third of normal within a short period after the onset of immune-related diabetes, and neither of the measures returns to normal ( 26 ). The C-peptide levels in the patient in this case were also significantly decreased to less than one-third of normal and did not recover in the long term; thus, we considered that dynamic monitoring of changes in the C-peptide levels during PM8001 treatment might be an important strategy for predicting immune-related T1DM.…”

A new era in cancer treatment: harnessing ZIF-8 nanoparticles for PD-1 inhibitor delivery

“…7). 23,[144][145][146][147] KN046@ 19 F-ZIF-8, a combination of KN046 and ZIF-8, offers several advantages in cancer treatment. It boosts the immune response by activating T cells to target cancer cells more effectively.…”