Remestemcel-L for the treatment of graft versus host disease

Introduction: Remestemcel-L, a third-party, off-the-shelf preparation of bone-marrow derived mesenchymal stromal cells (MSCs), has been developed for experimental use in acute graft-versus-host disease (aGvHD) and other immune-mediated conditions. Several preclinical and clinical studies have indeed suggested the potential of human mesenchymal stromal cells (MSCs) as an effective treatment for steroid-refractory aGvHD. However, an unambiguous demonstration of efficacy is still lacking. Areas covered: This review critically examines the biologic rationale supporting MSCs use in aGvHD and analyzes the results of published clinical trials in this setting, with a particular focus on the potential benefits and drawbacks of Remestemcel-L. For this purpose, a systematic literature search was performed in PubMed using the following keywords: ‘mesenchymal stromal cells’, ‘mesenchymal progenitor cells’, ‘multipotent stromal cells’, ‘mesenchymal cells’, ‘MSC’, ‘Remestemcel-L’, ‘Prochymal’, and ‘graft-versus-host disease’ or ‘GvHD’. Expert commentary: Remestemcel-L represents a promising alternative to second-line immunosuppressive agents for the treatment of steroid-refractory aGvHD. Despite the safety and the favorable risk/benefit profile of this cell product, which has been demonstrated in several phase I-II studies, large and prospective randomized trials are required to confirm its efficacy in aGvHD and to define the optimal schedule of administration in terms of infusion timing, cell dose and pharmacological synergism.