Bortezomib for the prevention and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

• Bortezomib posses a number of immunomodulatory effects that span a wide range of cellular processes of T and dendritic cells.
• Murine and early clinical studies suggest that while bortezomib ameliorates GvHD when administered early post-transplant, it paradoxically accelerates GvHD when administered late.
• The optimal use of bortezomib in the prevention and treatment of GvHD requires further examination.

Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting.