EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation
Lauren P McLaughlin, Rayne Rouce, Stephen Gottschalk, Vicky Torrano, George Carrum, Meng-Fen Wu, Fahmida Hoq, Bambi Grilley, Andrea M Marcogliese, Patrick J Hanley, Adrian P Gee, Malcolm K Brenner, Cliona M Rooney, Helen E Heslop, Catherine M Bollard, Lauren P McLaughlin, Rayne Rouce, Stephen Gottschalk, Vicky Torrano, George Carrum, Meng-Fen Wu, Fahmida Hoq, Bambi Grilley, Andrea M Marcogliese, Patrick J Hanley, Adrian P Gee, Malcolm K Brenner, Cliona M Rooney, Helen E Heslop, Catherine M Bollard
Abstract
Autologous T cells targeting Epstein-Barr virus (EBV) latent membrane proteins (LMPs) have shown safety and efficacy in the treatment of patients with type 2 latency EBV-associated lymphomas for whom standard therapies have failed, including high-dose chemotherapy followed by autologous stem-cell rescue. However, the safety and efficacy of allogeneic donor-derived LMP-specific T cells (LMP-Ts) have not been established for patients who have undergone allogeneic hematopoietic stem-cell transplantation (HSCT). Therefore, we evaluated the safety and efficacy of donor-derived LMP-Ts in 26 patients who had undergone allogeneic HSCT for EBV-associated natural killer/T-cell or B-cell lymphomas. Seven patients received LMP-Ts as therapy for active disease, and 19 were treated with adjuvant therapy for high-risk disease. There were no immediate infusion-related toxicities, and only 1 dose-limiting toxicity potentially related to T-cell infusion was seen. The 2-year overall survival (OS) was 68%. Additionally, patients who received T-cell therapy while in complete remission after allogeneic HSCT had a 78% OS at 2 years. Patients treated for B-cell disease (n = 10) had a 2-year OS of 80%. Patients with T-cell disease had a 2-year OS of 60%, which suggests an improvement compared with published posttransplantation 2-year OS rates of 30% to 50%. Hence, this study shows that donor-derived LMP-Ts are a safe and effective therapy to prevent relapse after transplantation in patients with B cell- or T cell-derived EBV-associated lymphoma or lymphoproliferative disorder and supports the infusion of LMP-Ts as adjuvant therapy to improve outcomes in the posttransplantation setting. These trials were registered at www.clinicaltrials.gov as #NCT00062868 and #NCT01956084.
Conflict of interest statement
Conflict-of-interest disclosure: C.M.B. is on the scientific advisory boards of Cellectis, Torque, and Neximmune and has stock or ownership in Mana Therapeutics; S.G. has a consulting or advisory role with AbbVie, Celgene, and Merrimack Pharmaceuticals and several patent applications (8 focused on cell therapy for cancer, 1 focused on oncolytic viruses, and 1 focused on cancer gene therapy); M.K.B. has stock or ownership in Viracyte and Marker Therapeutics, has a consulting or advisory role with Torque, Unum, and Tessa Therapeutics, and receives research funding from Cell Medica and Tessa Therapeutics; H.E.H. has stock or ownership in Viracyte and Marker Therapeutics, has a consulting or advisory role with Gilead and Novartis, receives research funding from Cell Medica and Tessa Therapeutics, and has patents/royalties/other intellectual property through Cell Medica; C.M.R. has stock or ownership in Viracyte and Marker Therapeutics, has a consulting or advisory role with Cell Medica, CellGenix, and Tessa Therapeutics, receives research support from Tessa Therapeutics, and has a patent application in the field of cellular immunotherapy; and R.R. has received honoraria for serving on a Novartis Treatment Advisory Landscape Advisory Board regarding CAR T-cell commercialization. The remaining authors declare no competing financial interests.
© 2018 by The American Society of Hematology.
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Source: PubMed