In recent years the use of immunomodulating therapy to treat various cancers has been on the rise. Three checkpoint inhibitors have been approved by the Food and Drug Administration (ipilimumab, pembrolizumab and nivolumab). The use of these drugs comes with serious adverse events related to excessive immune activation, collectively known as immune-related adverse events (irAEs). We conducted a system-based review of 139 case reports/case series that have described these adverse events between January 2016 and April 2018, found in the PubMed database. There was a broad spectrum of presentations, doses and checkpoint inhibitors used. The most common check point inhibitor observed in our literature review was nivolumab. The most common adverse effects encountered were colitis (14/139), hepatitis (11/139), adrenocorticotropic hormone insufficiency (12/139), hypothyroidism (7/139), type 1 diabetes (22/139), acute kidney injury (16/139) and myocarditis (10/139). The treatment most commonly consisted of cessation of the immune checkpoint inhibitor, initiation of steroids and supportive therapy. This approach provided a complete resolution in a majority of cases; however, there were many that developed long-term adverse events with deaths reported in a few cases. The endocrine system was the mostly commonly affected with the development of type 1 diabetes mellitus or diabetic ketoacidosis being the most frequently reported adverse events. While immunomodulating therapy is a significant advance in the management of various malignancies, it is capable of serious adverse effects. Because the majority of the cases developed pancreatic dysfunction within five cycles of therapy, in addition to the evaluation of other systems, pancreatic function should be closely monitored to minimize adverse impact on patients.

The utility of immunotherapy, such as pembrolizumab, is becoming essential in the treatment of certain cancers. Pembrolizumab works through binding of programmed cell death 1 receptor that blocks the binding of the programmed cell death ligand 1 and is commonly used in non-small cell lung cancer and melanoma. Pembrolizumab has been reported to be associated with multiple adverse reactions such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes; however, pembrolizumab causing type 1 diabetes was only reported in 0.1% of the patients in clinical trials. A review of the literature generated 1,001 unique citations of which six reported cases of autoimmune diabetes associated with pembrolizumab were selected and compared. Review of the cases showed no sexual predilection and the average age of onset was 58 years old. The majority of the patients were treated for melanoma (5/6 cases), initially presented with diabetic ketoacidosis (4/6 cases), and had at one point taken ipilimumab (4/6 cases). There was no association found between the number of treatments received and the development of diabetes. With the increasing use of pembrolizumab in cancer treatment regular blood glucose monitoring during treatment, especially in patients who had also taken ipilimumab, may prevent the onset of this life-threatening complication.

e15148 Background: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) are caused by non-specific immune system activation and develop in 30-70% of patients. The goal of this study is to examine the association of race with the development of irAEs secondary to ICIs as autoimmune diseases generally exhibit racial differences. Methods: A retrospective chart review was done using University of Louisville pharmacy database. Patients with solid cancers who received ICIs between Jan 2016 to June 2019 were included. IrAEs were identified through the review of electronic medical records. Descriptive analysis evaluated the incidence and severity of irAEs. Multivariable logistic regression was used to calculate standardized incidence of irAEs among Whites and African Americans. Results: A total of 476 patients were included in this study. The mean age was 61 years, 57% were males and 89.7% were whites. A majority of patients had melanoma (50%). The remainder of the dataset included lung (33.4%), gastrointestinal (7.4%), head & neck (4.8%), breast (2.5%) and genitourinary (1.9%) cancers. ICIs included single agent anti-PD-1 (74.8%), single agent anti-PD-L1 (9.4%), combination anti-CTLA-4 with anti-PD-1 (7.1%). Some patients were also treated with > 1 ICI as subsequent therapy (8.6%). Overall, the rate of irAEs was 44.3% with 33.8% grade 1-2 and 12.4% grade 3-4 irAEs. There was no difference in development of any grade irAEs in Whites as compared to African Americans after adjusting for age, sex, cancer type and ICIs (44.3% vs 44.2%; OR: 0.99, 95% CI: 0.50 – 1.97; p = 0.99). There was also no difference in development of grade 3-4 irAEs in whites as compared to African Americans (12.8% vs 14.5%; OR: 1.16, 95% CI: 0.43 – 3.12; p = 0.75). Conclusions: In this study, we found no racial difference in the development of irAEs between Whites and African Americans. This is in contrast to general autoimmune diseases which exhibit racial differences with higher prevalence among African Americans compared to Whites. We will continue to accrue patients to this study as larger sample size is needed to confirm these findings.

Duplication of the inferior vena cava (DIVC) is an uncommon embryological anatomic phenomenon.We report a 63-year-old woman with extensive right leg deep vein thrombosis who required an IVC filter due to contraindications for anticoagulation, but was found to have DIVC which required the placement of two IVC filters with good result. This report will review and summarise past reports of DIVC management to provide a guide for future clinicians, and review the embryological development, diagnosis and IVC filter placement options as they are based on the type of anatomic malformation encountered.