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Chronic graft-versus-host disease: newer treatment strategies

Feb 6, 2019

It has been shown that the pathobiology of chronic graft-versus-host disease (cGvHD) involves a complex interplay between the immune systems of the donor and the recipient. Donor-derived T cells play a major role in cGvHD as the preeminent mediators, however, aberrant B cells also contribute to the pathogenesis of cGvHD by increasing inflammation and autoimmunity, as well as vulnerability to severe infections. Corticosteroids are the accepted first-line therapy, with or without other immunosuppressive agents for the treatment of cGvHD. If a patient is refractory to steroids or has progressive disease, second-line treatment is required. Despite significant progress in the development of effective second-line treatments for steroid-refractory cGvHD, the response rate to second-line therapy is approximately 25–50%, with no significant differences between therapy options. Ibrutinib is currently approved in the US for the treatment of cGvHD after failure of one or more lines of systemic therapy, however, there is an unmet need in the development of novel treatment strategies to improve post-transplant outcomes. Please see the current novel therapy options in the downloadable table below:

  1. Hill L. et al. New and emerging therapies for acute and chronic graft versus host disease. Ther Adv Hematol.2018 Jan;9(1):21-46. DOI: 10.1177/2040620717741860. Epub 2017 Nov 28.
  2. Presland B. Biology of chronic graft-vs-host disease: Immune mechanisms and progress in biomarker discovery. World J Transplant. 2016 Dec 24; 6(4): 608–619. DOI: 10.5500/wjt.v6.i4.608.
  3. Sarantopoulos S. et al.Aberrant B-cell homeostasis in chronic GvHD. Blood. 2015 125:1703-1707; DOI: 10.1182/blood-2014-12-567834.
  4. Choi J. et al. IFNγR signaling mediates alloreactive T-cell trafficking and GvHD. 2012 Nov 8;120(19):4093-103. DOI: 10.1182/blood-2012-01-403196. Epub 2012 Sep 12.
  5. Wolff D. et al.The treatment of chronic graft-versus-host disease: consensus recommendations of experts from Germany, Austria, and Switzerland. Dtsch Arztebl Int. 2011 Oct;108(43):732-40. DOI: 10.3238/arztebl.2011.0732. Epub 2011 Oct 28.
  6. Miklos D. et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017 June; 793786. DOI: 10.1182/blood-2017-07-793786.
  7. Le Huu D. et al. Blockade of Syk ameliorates the development of murine sclerodermatous chronic graft-versus-host disease. J Dermatol Sci. 2014 Jun;74(3):214-21. DOI: 10.1016/j.jdermsci.2014.02.008. Epub 2014 Mar 12.
  8. Flynn R. et al. Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood. 2016 Apr 28;127(17):2144-54. DOI: 10.1182/blood-2015-10-678706. Epub 2016 Mar 16.