Programmed Cell Death-1 Monoclonal Antibody Therapy and Type 1 Diabetes Mellitus: A Review of the Literature

Abstract

Two Food and Drug Administration-approved programmed cell death-1 (PD-1) inhibitors, nivolumab (Opdivo®), and pembrolizumab (Keytruda®), are indicated for treatment-resistant malignancies. Inhibition of PD-1 also inhibits T-cell peripheral tolerance, enhancing autoimmunity. Various autoimmune conditions have been reported with the use of these agents, including type 1 diabetes mellitus (T1DM). This article reviews literature regarding the development of T1DM in patients treated with PD-1 inhibitors and identifies strategies for the appropriate identification, monitoring, and follow-up of these patients. Published cases of T1DM related to PD-1 inhibitor therapy were identified using PubMed. Eighty-three identified publications were reviewed, of which 37 publications involving 42 cases of anti-PD-1 therapy-induced T1DM were identified. The average age of patients at presentation was 62 years and 59.5% were male. The mean number of PD-1 inhibitor doses received was 5, with a mean time to presentation of 11 weeks. Initial presentation of diabetic ketoacidosis was reported in 69% of cases, with an average blood glucose of 660 mg/dL and an average HbA_1c of 8.7%. The exact mechanism PD-1 inhibitor therapy-induced T1DM is unknown. Blood glucose monitoring is recommended for all patients receiving anti-PD-1 therapy. Further research is needed to delineate the frequency of this adverse effect, as well as to evaluate potential risk factors and ideal management strategies.