Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Adult, Diseases, Non-Biological, Therapies, GVHD, Biological Processes, Immune Disorders, Study Population, Clinically relevant, Quality Improvement , pharmacology, inflammation, proteomics
Previous studies have demonstrated that a panel measuring the plasma levels of ST2, REG3A, and TNFR1 can be utilized to distinguish steroid treated subjects with an increased risk of progressive aGVHD; however, it is unknown if these biomarkers are predictive of response to the combination of corticosteroids and itacitinib. In this study, we compared the plasma levels of ST2, REG3A, TNFR1, and Trappin-2/Elafin in order to distinguish response to combination treatment. Additionally, we conducted a broad proteomic analysis to identify potential prognostic biomarkers of response to the combination treatment.
METHODS: Plasma samples were collected from 31 subjects enrolled in the Phase 1 clinical trial prior to and at designated times following treatment. Levels of REG3A, ST2, TNFR1, and Trappin-2/Elafin were measured using SimplePlex multiplex platform based on manufacturer instructions. Broad proteomic analysis was additionally conducted by OLINK Proteomics using a proximity extension assay. Statistical differences were identified using unpaired T tests and significance conferred when p<0.05. All subjects provided written consent prior to enrollment.
RESULTS: Subjects were separated into responders (10- Complete Responder, 1-Very Good Partial Responder, 8-Partial Responder) and non-responders (2-Mixed Responder, 10-Progressive Disease/Death) based on CIBMTR response criteria at day 28. Levels of ST2 and TNFR1 were significantly elevated at baseline in non-responders (p<0.05 for both ST2 and TNFR1) when compared with responders (Table 1). Additionally, baseline levels of ST2 and TNFR1 significantly correlated (p<0.0001 for both ST2 and TNFR1) with the Minnesota and CIBMTR response criteria for aGVHD. There were no significant differences in the levels of REG3A and Trappin-2/Elafin between responders and non-responders.
Novel biomarkers were identified and associated with therapeutic response by comparing the levels of approximately 1000 proteins in the CR and PD/Death cohorts specifically. The initial analysis identified 44 proteins significantly upregulated (p<0.05; fold change > 1.5) and 61 proteins significantly down-regulated (p<0.05; fold change < -1.5) in the CR cohort at baseline compared with the PD/Death cohort. Further analysis of the CR cohort identified 23 proteins significantly modulated (Fold Change > |1.5|, p<0.05) between baseline and day 28 samples which may serve as additional biomarkers of therapeutic response.
CONCLUSION: Proteomic analysis of clinical samples confirmed the value of ST2 and TNFR1 in predicting response to treatment with itacitinib and steroids and also identified a number of novel plasma biomarkers that may have utility in selecting and/or monitoring aGVHD subjects when treated with a combination of corticosteroids and itacitinib.
Disclosures: Pratta: Incyte Research Institute: Employment, Equity Ownership. Liu: Incyte Research Institute: Employment, Equity Ownership. Arbushites: Incyte Corporation: Employment, Equity Ownership. Newton: Incyte Research Institute: Employment, Equity Ownership. Howell: Incyte Research Institute: Employment, Equity Ownership.
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