The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells

Blood. 2019 Apr 25;133(17):1876-1887. doi: 10.1182/blood-2018-11-887067. Epub 2019 Feb 19.


Factors associated with durable remission after CD19 chimeric antigen receptor (CAR)-modified T-cell immunotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) have not been identified. We report multivariable analyses of factors affecting response and progression-free survival (PFS) in patients with aggressive NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by 2 × 106 CD19-directed CAR T cells/kg. The best overall response rate was 51%, with 40% of patients achieving complete remission. The median PFS of patients with aggressive NHL who achieved complete remission was 20.0 months (median follow-up, 26.9 months). Multivariable analysis of clinical and treatment characteristics, serum biomarkers, and CAR T-cell manufacturing and pharmacokinetic data showed that a lower pre-lymphodepletion serum lactate dehydrogenase (LDH) level and a favorable cytokine profile, defined as serum day 0 monocyte chemoattractant protein-1 (MCP-1) and peak interleukin-7 (IL-7) concentrations above the median, were associated with better PFS. MCP-1 and IL-7 concentrations increased after lymphodepletion, and higher intensity of cyclophosphamide and fludarabine lymphodepletion was associated with higher probability of a favorable cytokine profile. PFS was superior in patients who received high-intensity lymphodepletion and achieved a favorable cytokine profile compared with those who received the same intensity of lymphodepletion without achieving a favorable cytokine profile. Even in high-risk patients with pre-lymphodepletion serum LDH levels above normal, a favorable cytokine profile after lymphodepletion was associated with a low risk of a PFS event. Strategies to augment the cytokine response to lymphodepletion could be tested in future studies of CD19 CAR T-cell immunotherapy for aggressive B-cell NHL. This trial was registered at as #NCT01865617.

Publication types

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

MeSH terms

  • Antigens, CD19 / immunology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cell- and Tissue-Based Therapy / methods*
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy / methods*
  • Lymphocyte Depletion / methods*
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / mortality*
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Receptors, Antigen, T-Cell / immunology*
  • Survival Rate
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives


  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Cyclophosphamide
  • Vidarabine
  • fludarabine

Associated data