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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 adjuvant therapy to prevent relapse after allogeneic HSCT for EBV-associated lymphomas.

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

There is a Blood Commentary on this article in this issue.

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.

  • Submitted July 15, 2018.
  • Accepted September 13, 2018.
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