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Current and Emerging Targeted Therapies for Acute Graft-Versus-Host Disease

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Abstract

Acute graft-versus-host disease (GVHD), the major complication after allogeneic hematopoietic cell transplant (HCT), develops in approximately 50% of patients. The primary treatment is high-dose systemic steroids, but treatment failure is common, and steroid-refractory (SR) GVHD is the leading cause of non-relapse mortality after allogeneic HCT. Ruxolitinib became the first treatment for SR GVHD to obtain US Food and Drug Administration approval, and other new treatments are actively being studied. We searched the literature using the PubMed database and clinical trials using ClinicalTrials.gov to identify the most promising new treatments for GVHD. In this review, we categorize potential new treatments for GVHD by their mechanism of action (e.g., antibodies that deplete T cells or prevent their trafficking to target tissues, proteasome inhibitors, tyrosine kinase inhibitors, and other agents) and summarize the results from clinical trials.

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  1. Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA

    Stelios Kasikis, Aaron Etra & John E. Levine

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  1. Stelios Kasikis
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  2. Aaron Etra
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National Cancer Institute (P01CA03942 and P30CA196521), Pediatric Cancer Foundation.

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SK and AE report no conflicts of interest. JEL reports royalties from a GVHD biomarker patent, research support from Biogen, Incyte, and Kamada, and consulting fees from Bluebird, Incyte, Ironwood, Mesoblast, Novartis, Omeros, Oncoimmue, Talaris, and X4 Pharmaceuticals.

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JEL was invited to provide the review. SK, AE, and JEL performed the literature review and wrote the manuscript. All authors take responsibility for the final version of the paper.

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Kasikis, S., Etra, A. & Levine, J.E. Current and Emerging Targeted Therapies for Acute Graft-Versus-Host Disease. BioDrugs 35, 19–33 (2021). https://doi.org/10.1007/s40259-020-00454-7

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