High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients

Leukemia. 2017 Dec;31(12):2587-2593. doi: 10.1038/leu.2017.145. Epub 2017 May 15.

Abstract

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 105/kg and were eventually settled at 1 × 105/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 105/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, CD19 / immunology*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Cohort Studies
  • Combined Modality Therapy / methods
  • Disease Models, Animal
  • Drug Resistance, Neoplasm
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Heterografts
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Male
  • Mice
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Recurrence
  • T-Cell Antigen Receptor Specificity / genetics
  • T-Cell Antigen Receptor Specificity / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Treatment Outcome
  • Young Adult

Substances

  • Antigens, CD19