Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

J Clin Oncol. 2021 Oct 20;39(30):3352-3363. doi: 10.1200/JCO.21.00917. Epub 2021 Aug 31.


Purpose: Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL.

Methods: Patients age ≥ 16 years with r/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years.

Results: Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had ≥ 50% bone marrow blasts. No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease-negative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4%-84.4%) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies/µg genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up.

Conclusion: AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Agammaglobulinemia / etiology
  • Antigens, CD19 / immunology*
  • B-Lymphocytes / pathology
  • Bone Marrow / pathology
  • Cytokine Release Syndrome / etiology
  • Female
  • Graft vs Host Disease / etiology
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Infections / etiology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Nervous System Diseases / etiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Progression-Free Survival
  • Receptors, Chimeric Antigen / immunology*
  • Recurrence
  • Retreatment
  • Survival Rate
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation*
  • Transplantation, Autologous / adverse effects
  • Treatment Outcome
  • Young Adult


  • Antigens, CD19
  • CD19 molecule, human
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT02935257