Low-Dose ATG/PTCy Plus Ivarmacitinib for aGVHD Prevention in Haplo-PBSCT From Parous Female Donors

Summary

Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly affecting survival and quality of life. Acute GVHD (aGVHD) typically occurs within 100 days post-transplant, commonly involving skin, gastrointestinal tract, and liver. Chronic GVHD (cGVHD) can appear months to years later. Despite prophylaxis with calcineurin inhibitors (e.g., cyclosporine or tacrolimus), methotrexate, mycophenolate mofetil, and post-transplant cyclophosphamide (PTCy), patients receiving haploidentical transplantation from parous female donors remain at high risk for moderate-to-severe aGVHD. JAK1-dependent cytokine signaling (IL-6, IFN-γ) is central to GVHD pathogenesis. Selective JAK1 inhibition may attenuate T cell-mediated inflammation while preserving hematopoiesis. Ivarmacitinib (SHR0302) is a highly selective oral JAK1 inhibitor, showing favorable safety and preliminary efficacy in autoimmune and GVHD settings, making it a candidate for early GVHD prophylaxis.

Timeline

Start

2026-05-01

Primary completion

2028-05-01

Completion

2029-05-01

Publications

• Background He Q, Sun X, Niu J, Yang J, Wang Y, Huang C, Zhou K, Tong Y, Cai Y, Dong B, Wan L, Song X, Qiu H. A Novel JAK1 Inhibitor SHR0302 Combined With Prednisone for First-Line Treatment of Chronic Graft-Versus-Host Disease: A Phase I Clinical Trial. Cell Transplant. 2024 Jan-Dec;33:9636897241254678. doi: 10.1177/09636897241254678.
• Background Sun X, He Q, Yang J, Wang A, Zhang F, Qiu H, Zhou K, Wang P, Ding X, Yuan X, Li H, Zhang Y, Song X. Preventive and Therapeutic Effects of a Novel JAK Inhibitor SHR0302 in Acute Graft-Versus-Host Disease. Cell Transplant. 2021 Jan-Dec;30:9636897211033778. doi: 10.1177/09636897211033778.
• Background Schroeder MA, Khoury HJ, Jagasia M, Ali H, Schiller GJ, Staser K, Choi J, Gehrs L, Arbushites MC, Yan Y, Langmuir P, Srinivas N, Pratta M, Perales MA, Chen YB, Meyers G, DiPersio JF. A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease. Blood Adv. 2020 Apr 28;4(8):1656-1669. doi: 10.1182/bloodadvances.2019001043.
• Background Kim S, Ashami K, Lim S, Staser K, Vij K, Santhanam S, Ritchey J, Peterson S, Gao F, Ciorba MA, Cooper ML, DiPersio JF, Choi J. Baricitinib prevents GvHD by increasing Tregs via JAK3 and treats established GvHD by promoting intestinal tissue repair via EGFR. Leukemia. 2022 Jan;36(1):292-295. doi: 10.1038/s41375-021-01360-9. Epub 2021 Jul 24. No abstract available.
• Background Loren AW, Bunin GR, Boudreau C, Champlin RE, Cnaan A, Horowitz MM, Loberiza FR, Porter DL. Impact of donor and recipient sex and parity on outcomes of HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006 Jul;12(7):758-69. doi: 10.1016/j.bbmt.2006.03.015.
• Background Yang J, Jia Y, Hu X, Zhou F, Ni X, Wan J, Ding Y, Kang M, Yu X, Jiang C, Wang L, Wan L, Cai Y, Huang C, Qiu H, Ding X, Tong Y, Dong B, Zhou K, Song X. A randomized trial of GVHD prophylaxis in haploidentical PBSC transplantation: ATG, PTCy, and low-dose combination therapy. Blood. 2026 Jun 25;147(26):3168-3178. doi: 10.1182/blood.2025032569.
• Background Xu X, Yang J, Cai Y, Li S, Niu J, Zhou K, Jiang Y, Xu X, Shen C, Huang C, Qiu H, Wei D, Kang M, Tong Y, Wei Z, Liu P, Wan L, Song X. Low dose anti-thymocyte globulin with low dose posttransplant cyclophosphamide (low dose ATG/PTCy) can reduce the risk of graft-versus-host disease as compared with standard-dose anti-thymocyte globulin in haploidentical peripheral hematopoietic stem cell transplantation combined with unrelated cord blood. Bone Marrow Transplant. 2021 Mar;56(3):705-708. doi: 10.1038/s41409-020-01047-2. Epub 2020 Sep 1. No abstract available.
• Background Cooke KR, Luznik L, Sarantopoulos S, Hakim FT, Jagasia M, Fowler DH, van den Brink MRM, Hansen JA, Parkman R, Miklos DB, Martin PJ, Paczesny S, Vogelsang G, Pavletic S, Ritz J, Schultz KR, Blazar BR. The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2017 Feb;23(2):211-234. doi: 10.1016/j.bbmt.2016.09.023. Epub 2016 Oct 3.
• Background Blazar BR, Murphy WJ, Abedi M. Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol. 2012 May 11;12(6):443-58. doi: 10.1038/nri3212.
• Background Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009 May 2;373(9674):1550-61. doi: 10.1016/S0140-6736(09)60237-3. Epub 2009 Mar 11.

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