08.16.22

Biomarkers Identify acute GVHD response to Itacitinib

Pratta M, Paczesny S, Socie G, et al. A Biomarker Signature to Predict Complete Response to Itacitinib and Corticosteroids in Acute Graft-Versus-Host Disease. British Journal of Haematology. 2022; (doi: 10.1111/bjh.18300).

Researchers identified and assessed biomarkers that may predict acute graft-versus-host disease (GVHD) patients' response to itacitinib, an oral selective Janus kinase 1 (JAK1) inhibitor. The identification cohort included plasma samples from 25 individuals that were used to identify novel biomarkers tested in a validation cohort from a placebo-controlled, randomized trial with 210 participants. The identification cohort received corticosteroids plus itacitinib 200 mg or 300 mg once daily, while the validation cohort received corticosteroids plus itacitinib 200 mg once daily or placebo. Analysis identified seven candidate biomarkers. Monocyte-chemotactic protein (MCP)3, pro-calcitonin/calcitonin (ProCALCA/CALCA), along with regenerating islet-derived protein (REG)3A — a previously identified prognostic biomarker of acute GVHD — identified complete responders from non-responders to itacitinib, but not to placebo, suggesting possible predictive biomarkers of itacitinib in acute GVHD. Potential response-to-treatment biomarkers were seen in the significant reduction of ProCALCA/CALCA, suppressor of tumorigenicity (ST)2, and tumour necrosis factor receptor (TNFR)1 by itacitinib in responders.

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