Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia

Nat Commun. 2020 Nov 23;11(1):5928. doi: 10.1038/s41467-020-19774-x.

Abstract

CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Immunotherapy, Adoptive*
  • Male
  • Middle Aged
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Antigen, T-Cell / immunology
  • Recurrence
  • Remission Induction
  • Risk Factors
  • Safety
  • Survival Rate
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Young Adult

Substances

  • CD19-specific chimeric antigen receptor
  • Receptors, Antigen, T-Cell

Associated data

  • ClinicalTrials.gov/NCT02735291
  • figshare/10.6084/m9.figshare.13136078.v1