Effective Response and Delayed Toxicities of Refractory Advanced Diffuse Large B-cell Lymphoma Treated by CD20-directed Chimeric Antigen Receptor-Modified T Cells

Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.

Abstract

We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3ζ moiety in patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). Seven patients were enrolled. One of the two patients with no bulky tumor obtained a 14-month durable and ongoing complete remission by cell infusion only, and another attained a 6-month tumor regression. Four of five patients with bulky tumor burden were evaluable for clinical efficacy, three of which attained 3- to 6-month tumor regression. Delayed toxicities related to cell infusion are directly correlated to tumor burden and tumor-harboring sites, and mainly included cytokine release symptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract and aggressive intrapulmonary inflammation surrounding extranodal lesions. These results show firstly that anti-CD20 CART cells can cause prolonged tumor regression in combination with debulking conditioning regimens for advanced DLBCL. This study is registered at www.clinicaltrials.gov as NCT01735604.

Keywords: Anti-CD20 chimeric antigen receptor (CAR) T cells;; Delayed toxicities; Diffuse large B-cell lymphoma (DLBCL);; Refractory advanced;.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD20 / genetics
  • Antigens, CD20 / immunology*
  • Antigens, CD20 / metabolism
  • Cell Line
  • Combined Modality Therapy
  • Cytotoxicity, Immunologic
  • Female
  • Gene Dosage
  • Gene Order
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphocyte Count
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Large B-Cell, Diffuse / therapy*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Positron-Emission Tomography
  • Protein Binding
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • T-Cell Antigen Receptor Specificity / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism

Substances

  • Antigens, CD20
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 9

Associated data

  • ClinicalTrials.gov/NCT01735604