Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products

Acute graft-versus-host disease (GVHD) is a life-threatening complication that can develop after allogeneic hematopoietic stem cell transplantation. In particular, the prognosis of patients with steroid-refractory acute GVHD is extremely poor. Ryoncil™ (remestemcel-L), a human bone marrow-derived mesenchymal stem cell (MSC) product, failed to show superiority over placebo in patients with steroid-refractory acute GVHD, but it was approved for use in pediatric patients in Canada and New Zealand based on the results of a subgroup analysis. Temcell^®, an equivalent manufactured MSC product to remestemcel-L, was approved in Japan based on small single-arm studies by using a regulation for regenerative medicine in 2016. The efficacy of Temcell was evaluated in 381 consecutive patients treated with Temcell during the initial 3 years after its approval. Interestingly, its real-world efficacy was found to be equivalent to that observed in a prospective study of remestemcel-L with strict eligibility criteria. In this article, the potential of MSC therapy in the treatment of acute GVHD is discussed. A meticulous comparison of studies of remestemcel-L and Temcell, remestemcel-L/Temcell and ruxolitinib, and remestemcel-L/Temcell and thymoglobulin showed that the precise position of remestemcel-L/Temcell therapy in the treatment of acute GVHD remains to be determined.