Tabelecleucel: a new therapeutic option in refractory EBV-PTLD

Post-transplant lymphoproliferative disorder (PTLD) is classified as an immune-associated lymphoproliferative disease occurring after hematopoietic stem cells transplantation (HCT) or solid organ transplantation (SOT). Rituximab and reduction of immunosuppression are the first line therapy of EBV-DNA-emia and EBV-PTLD and are seen as the ‘gold standard’ in therapy of post-transplant EBV-related complications. In cases of failed first line therapy with rituximab, regardless of applied reduction of immunosuppression, refractory EBV-PTLD is diagnosed. Refractory EBV-PTLD has a poor outcome, with 2-year overall survival rates of 9.4% and 31.4% following HCT and SOT, respectively, in patients who have failed rituximab and/or chemotherapy. The main treatment options for patients with EBV-PTLD post-HCT who failed first line therapy include the use of EBV-specific cytotoxic T-lymphocytes (EBV-CTLs), which can be donor-derived, third-party donor, or of ‘off-the-shelf’ origin. Tabelecleucel is a T-cell product including EBV-specific T-cells originating from a third-party EBV-seropositive donor. These EBV-CTLs were stimulated with B-cells from the same donor, able to recognize B-cells infected with EBV, with no genetic modification used, and expanded in laboratory conditions. Tabelecleucel has been investigated as an ATMP (advanced therapy medicinal product), an on-demand, allogeneic T-cell immunotherapy for the potential treatment of EBV-positive malignancies and diseases. The aim of this narrative review was to assess the third-party donor ‘off-the-shelf’ cellular product of EBV-CTLs, tabelecleucel, as a therapeutic option of treatment for refractory or relapsing EBV-PTLD.