Predictive cytokine biomarkers for immune-related adverse events associated with immune checkpoint inhibitor therapy in Hodgkin lymphoma.

Abstract

e14651 Background: Immune checkpoint inhibitors (ICIs) show great promise in the treatment of relapsed/refractory classical Hodgkin Lymphoma (cHL) and are being considered for up-front treatment. However, use of ICIs can be limited by immune-related adverse events (irAEs). Identifying predictive biomarkers for the development of irAEs could identify high-risk patients to potentially mitigate AEs. Methods: Eighteen patients with cHL were included; 11 patients treated with ICIs (pembrolizumab, nivolumab and/or ipilimumab) as cases (Cohort A) and 7 patients treated with standard of care chemotherapy as controls (Cohort B). The electronic medical record was reviewed for patient clinical characteristics. T cell cytokine expression and autoantibody profiles were performed on baseline pre-ICI treatment peripheral blood plasma samples using Luminex technology in the NYU Langone Immune Monitoring Core Laboratory; cytokine expression was analyzed by 2-way ANOVA. Results: All patients treated with ICIs had been previously treated with other therapy as opposed to Cohort B which included all newly diagnosed patients. Eight patients developed irAEs, with rash being most frequent (n=5) (Table). Analysis of cytokines showed significant elevation in ITAC for irAE compared to no irAE (p<0.01). Increased IL-6, IL-13, and IL-17 expression and decreased MIP-1b expression in those with irAEs all trended towards significance. There was no identified correlation between autoantibodies and irAEs. Conclusions: irAEs can be a significant challenge in cHL patients treated with ICIs, causing comorbidities and limiting benefit from vital therapies. In patients who developed irAEs, we found a significant elevation in ITAC, a chemokine induced by IFN-gamma that attracts activated T cells. Other inflammatory cytokines such as IL-6, IL-13, IL-17, and MIP-1b trended towards significance, likely due to the small sample size. Expansion of this study in a larger cohort of patients is planned. [Table: see text]