EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation

Blood. 2018 Nov 29;132(22):2351-2361. doi: 10.1182/blood-2018-07-863654. Epub 2018 Sep 27.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / immunology
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / therapy*
  • Lymphoma, B-Cell / virology
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / therapy*
  • Lymphoma, T-Cell / virology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Transplantation, Homologous / methods
  • Treatment Outcome
  • Viral Matrix Proteins / immunology
  • Young Adult

Substances

  • Viral Matrix Proteins

Associated data

  • ClinicalTrials.gov/NCT00062868
  • ClinicalTrials.gov/NCT01956084