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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 and Catherine M. Bollard

Key points

  • Donor-derived LMP-Ts are safe when administered as an adjuvant therapy to prevent relapse after allo-HSCT for EBV-associated lymphomas.

  • Patients had a 2-year overall survival of 68% that improved to 78% when LMP-Ts were infused in the adjuvant setting.

Abstract

Autologous T cells targeting Epstein Barr virus (EBV) latent membrane proteins (LMPs) have shown safety and efficacy for the treatment of patients with type II latency EBV-associated lymphomas who have failed standard therapies, 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 received allogeneic HSCT. Thus, we evaluated the safety and efficacy of donor-derived LMP-Ts in 26 patients who had received an allogeneic hematopoietic stem cell transplant (HSCT) for EBV-associated T/NK or B cell lymphomas (NCT00062868, NCT01956084; ClinicalTrials.gov). Seven patients received LMP-Ts as therapy for active disease, and 19 were treated as adjuvant therapy for high-risk disease. There were no immediate infusion-related toxicities and only one dose-limiting toxicity potentially related to T cell infusion. The two-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 diseases (n=10) had a 2-year OS of 80%. Patients with T cell diseases had a 2 year OS of 60% which suggests an improvement compared to published post-transplant 2-year overall survival rates of 30-50%.1 Hence, this study shows that donor-derived LMP-Ts are a safe and effective therapy to prevent relapse after transplant in patients with B or T cell-derived EBV-associated lymphomas or lymphoproliferative disorders and supports the infusion of LMP-specific T cells as adjuvant therapy to improve outcomes in the post-transplant setting.

  • Submitted July 16, 2018.
  • Accepted September 13, 2018.