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 Brenner, Cliona M. Rooney, Helen Heslop, Catherine M. Bollard

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2351-2361
Number of pages11
JournalBlood
Volume132
Issue number22
DOIs
StatePublished - Nov 29 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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