Date of Award
1-1-2022
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
Department
Pharmacy Administration
First Advisor
John Bentley
Second Advisor
Sujith Ramachandran
Third Advisor
Yi Yang
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
To fill the gap in existing literature related to immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC), this dissertation focused on: 1) assessing the incidence, spectrum and risk factors for the development of irAEs; 2) assessing the clinical impact of irAE occurrence on survival and treatment discontinuation; 3) analyzing and estimating the incremental economic burden of irAEs among an older population in the United States (US). A retrospective cohort study was conducted using the SEER-Medicare 2020 linkage database in order to evaluate the three study objectives. The dissertation included 8,175 patients diagnosed with NSCLC aged 65 years or older who received one or more PD-1/PD-L1 inhibitor doses between March 1st 2015 and December 31st 2018. As a starting point, this study found that nearly half of older NSCLC patients experienced irAEs post-ICI treatment. In most cases, the first irAE occurs within six months of starting therapy, but it can occur for up to 12 months. The earliest onset of irAEs was hematological, followed by central nervous system, cardiac, pulmonary, renal, endocrine, and liver events. IrAEs affecting the GI system, the skin, and the musculoskeletal system occurred relatively late. Pneumonitis, hypothyroidism, arrhythmia, and acute kidney injury (AKI) were the most common IrAEs. IrAE incidence was higher among patients living in the Midwest and Northeast regions of the US, with lower socioeconomic status, undergoing certain ICI treatments, and having specific health conditions. Furthermore, this study suggests that irAEs are associated with an increased risk of death and ICI discontinuation. There is a correlation between worse outcomes in patients with pneumonitis, arrhythmia, AKI, hepatitis, and colitis. Patients with hypothyroidism and skin-related irAEs, however, were more likely to live longer and receive longer treatment durations. Finally, this study demonstrated that occurrence of irAEs led to higher healthcare resource utilization (HCRU) and costs (estimated incremental cost: $21804.50). Most of the cost increase was attributed to hospitalizations, followed by visits to offices and skilled nursing facilities. There was a substantial increase in costs associated with managing the specific irAEs, which ranged from $1,765.91 to $8,975.99 per month. IrAEs with the highest costs include pneumonia, arrhythmia, AKI, and hepatitis. An extensive analysis of the characteristics, risk factors, and clinical and economic impact of irAEs in older NSCLC patients was conducted in this study. The findings of this study can be used by patients, clinicians, and payers to provide guidance on treatment options, to predict and prevent irAEs during immunotherapy, and to weigh the relative risk and benefit of ICIs for older adults with NSCLC.
Recommended Citation
Rong, Yiran, "Immune-Related Adverse Events of Immune Checkpoint Inhibitors: Incidence, Risk Factors, Clinical Outcomes, and Economic Burden in Older Adults with Non-Small Cell Lung Cancer" (2022). Electronic Theses and Dissertations. 2456.
https://egrove.olemiss.edu/etd/2456
Accessibility Status
Searchable text
Concentration/Emphasis
Pharmacy Administration