Measuring Markers of Immune Response in Patients Treated with Nivolumab (Opdivo®) and Pembrolizumab (Keytruda®)
Immune checkpoint inhibitors (ICIs) have drastically improved the clinical outcome for many cancer patients. However, not all patients treated with ICIs show a clinical response and the development of a unique spectrum of adverse events, termed immune-related adverse events (irAEs), restricts their oncological applicability. Additionally, the production of anti-drug antibodies (ADAs) may negatively influence patient outcome, but their role during therapy is yet to be established due to limitations in standard detection techniques. The primary aim of this exploratory study was to identify biomarkers that predict patient outcome to prevent a proportion of individuals exposed to a potentially ineffective and/or harmful therapy. It was hypothesized that patients who develop anti-drug antibodies experience a decrease in treatment efficacy and/or an increase in toxicity. Furthermore, patients with differing outcomes in terms of response, survival and the development of toxicity may display distinct clinicopathological characteristics. A retrospective review was performed on 32 patients undergoing nivolumab or pembrolizumab monotherapy for metastatic melanoma. Blood serum trough samples from 8 pembrolizumab-treated patients were analysed using in-house developed ELISA’s to measure pembrolizumab and anti-pembrolizumab antibody levels. Of the patients reviewed, 23 (72%) were ineligible for inclusion in initial clinical trials of ICI drugs. 29 patients (91%) experienced irAEs and 13 (41%) progressed during treatment. No clinicopathological variables were found to significantly predict patient outcome. Anti-pembrolizumab antibodies were detected in one patient and correlated with decreased blood serum drug levels. In this patient case, the individual responded to treatment according to RECIST, but, developed irAEs (pneumonitis and infusion reactions). This study indicates that, patients who are ineligible for initial clinical trials may effectively be treated with immune checkpoint inhibitors. Further investigation in a larger cohort is required to determine the prevalence and role of anti-ICI antibodies during ICI-therapy.
Advisor: Currie, Margaret; Hock, Barry; Strother, Matthew
Degree Name: Bachelor of Biomedical Sciences with Honours
Degree Discipline: Department of Pathology
Publisher: University of Otago
Research Type: Thesis