Determination of anti-pancreatic islet cell antibodies for the prevention of type 1 diabetes mellitus as an immune-related adverse event secondary to treatment with immune checkpoint inhibitors

Abstract

Abstract Background Type 1 diabetes mellitus (T1D) as an immune-mediated effect of immunotherapy-based oncology treatments is observed in 0.5-5% of the patients. Prevention of these symptoms is based on the determination of the basal sugar levels on an empty stomach after the administration of each dose of the drug. The objective of this clinical review is assessing the incorporation of anti-pancreatic islet cell antibodies in the prevention of these events. Methods A clinical review was carried out with the published cases of T1D secondary to immunotherapy between the years 2012 and 2019 in the current medical literature. We analyzed the determination of anti-pancreatic islet cell antibodies in patients who presented diabetes as an immune-mediated effect, as well as their phenotypic characteristics, the analysis levels and the drugs that had been used. Results Between 2012 and 2019 a total of 81 cases have been reported. The two most commonly described molecules were Nivolumab and Pembrolizumab (72/81, 90%), with an average age of 67 years and a predominance of men. Anti-b cell antibodies were observed in 36/81 patients (44%), with a similar frequency between the monotherapy group (31/70, 44%) and the group with combined therapy of anti-CTLA4 and anti-PD1 or PDL1 (5/11, 45%). The most commonly found antibody related to these events was antiglutamic acid decarboxylase (GAD) (34/81, 42%). No antibodies were found prior to the administration of the drug. Table . 65P Diabetes-related autoantibodies • Anti-GAD 34/81 (42%) • Anti-islet cell antibody (ICA) 1/81 (1.2%) • Anti-insulin antibody (IAA) 2/81 (2.5%) • Anti-islet antigen 2 antibody (IA2A) 4/81 (5%) • Anti-zinc transporter 8 antibody (ZnT8A) 1/81 (1.2%) Conclusion Determining the level of antibodies related to diabetes prior to the treatment with immunotherapy and during the treatment may prevent immunemediated diabetes. An assessment of the positivity of antibodies at the beginning of the treatment or of seroconversion during administration (as described in the literature) may have an influence on the detection of the development of T1D. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.