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

Craig S. Sauter, Brigitte Senechal, Isabelle Rivière, Ai Ni, Yvette Bernal, Xiuyan Wang, Terence Purdon, Malloury Hall, Ashvin N. Singh, Victoria Z. Szenes, Sarah Yoo, Ahmet Dogan, Yongzeng Wang, Craig H. Moskowitz, Sergio Giralt, Matthew J. Matasar, Miguel Angel Perales, Kevin J. Curran, Jae Park, Michel SadelainRenier J. Brentjens

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)626-635
Number of pages10
JournalBlood
Volume134
Issue number7
DOIs
StatePublished - Aug 15 2019
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sauter, C. S., Senechal, B., Rivière, I., Ni, A., Bernal, Y., Wang, X., Purdon, T., Hall, M., Singh, A. N., Szenes, V. Z., Yoo, S., Dogan, A., Wang, Y., Moskowitz, C. H., Giralt, S., Matasar, M. J., Perales, M. A., Curran, K. J., Park, J., ... Brentjens, R. J. (2019). CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Blood, 134(7), 626-635. https://doi.org/10.1182/blood.2018883421