Steroid-refractory chronic graft-versus-host disease: treatment options and patient management

Daniel Wolff, Giancarlo Fatobene, Vanderson Rocha, Nicolaus Kröger, Mary E Flowers, Daniel Wolff, Giancarlo Fatobene, Vanderson Rocha, Nicolaus Kröger, Mary E Flowers

Abstract

Chronic graft-versus-host disease (cGVHD) is one of the major causes of late mortality after allogenic hematopoietic stem cell transplantation. Moderate-to-severe cGVHD is associated with poor health-related quality of life and substantial disease burden. While corticosteroids with or without calcineurin inhibitors comprise the first-line treatment option, the prognosis for patients with steroid-refractory cGVHD (SR-cGVHD) remains poor. The mechanisms underlying steroid resistance are unclear, and there are no standard second-line treatment guidelines for patients with SR-cGVHD. In this review, we provide an overview on current treatment options of cGVHD and use a series of theoretical case studies to elucidate the rationale of choices of second- and third-line treatment options for patients with SR-cGVHD based on individual patient profiles.

Conflict of interest statement

D.W. has received honoraria from MACO, Mallinckrodt, Neovii Pharmaceuticals, Novartis AG, and Takeda Pharmaceutical Company Limited. G.F. has an advisory role and has served on speakers’ bureaus for Janssen Global Services LLC. N.K. has received research support from Celgene, Novartis AG and RIEMSER Pharma GmbH; speaker honoraria from Bristol-Myers Squibb Company, Celgene Corporation, Gilead Sciences Inc., Janssen Global Services LLC, Kite, Neovii Pharmaceuticals, Novartis AG, and Sanofi. MEF has received research support from Incyte and Pharmacyclics LLC including AbbVie Inc.; speaker honoraria from Astellas Pharma US, Inc., Janssen Global Services LLC, and Mallinckrodt; and served as a consultant for CSL Behring, Fresenius Kabi AG, and Pharmacyclics LLC. V.R. has no conflict of interest to report.

© 2021. The Author(s).

Figures

Fig. 1. Biologic phases of c-GVHD with…
Fig. 1. Biologic phases of c-GVHD with agents added targeting specific pathways (modified version derived from Cooke 2017 [24]).
CNI calcineurin inhibitors, cyclo. cyclophosphamide, ECP extracorporeal photopheresis, IL-2 interleukin-2, IL17 interleukin 17, imids immunomodulatory imide drugs, MMF mycophenolate mofetil, MSC mesenchymal stromal cells, mTOR-Inh. mechanistic target of rapamycin inhibitors, MTX methotrexate, PDGFα platelet-derived growth factor receptor alpha, TGFβ transforming growth factor β, TLR Toll-like receptor, TNFα tumor necrosis factor alpha, TNI total nodal irradiation. mTOR-Inh.: sirolimus, everolimus; imids: thalidomide, pomalidomide; proteosome inhibitors: bortezomib, ixazomib. It should be noted that listing of one target does not exclude additional targets in specific drugs (i.e. proteosome inhibitors target T cells, B cells, and plasma cells).

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