CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma Academic Article uri icon

Overview

MeSH Major

  • Lymph Nodes
  • Lymphoma, B-Cell, Marginal Zone
  • Waldenstrom Macroglobulinemia

abstract

  • © 2011 by The American Society of Hematology; all rights reserved. High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. Only 50% of patients are cured with this approach. We investigated safety and efficacy of CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT. Eligibility for this study includes poor-risk rel/ref aggressive B-cell non-Hodgkin lymphoma chemosensitive to salvage therapy with: (1) positron emission tomography-positive disease or (2) bone marrow involvement. Patients underwent standard HDT-ASCT followed by 19-28z CAR T cells on days 12 and 13. Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 3 106 and 1 3 107 19-28z CAR T per kilogram). Ten of 15 subjects experienced CAR T-cell-induced neurotoxicity and/or cytokine release syndrome (CRS), which were associated with greater CAR T-cell persistence (P 5 .05) but not peak CAR T-cell expansion. Serum interferon-g elevation (P < .001) and possibly interleukin-10 (P 5 .07) were associated with toxicity. The 2-year progression-free survival (PFS) is 30% (95% confidence interval, 20% to 70%). Subjects given decreased naive-like (CD45RA1CCR71) CD41 and CD81 CAR T cells experienced superior PFS (P 5 .02 and .04, respectively). There was no association between CAR T-cell peak expansion, persistence, or cytokine changes and PFS. 19-28z CAR T cells following HDT-ASCT were associated with a high incidence of reversible neurotoxicity and CRS. Following HDT-ASCT, effector CD41 and CD81 immunophenotypes may improve disease control. This trial was registered at www. clinicaltrials.gov as #NCT01840566.

publication date

  • August 15, 2019

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1182/blood.2018883421

PubMed ID

  • 31262783

Additional Document Info

start page

  • 626

end page

  • 635

volume

  • 134

number

  • 7