Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies
- 2 January 2020
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 135 (1), 17-27
- https://doi.org/10.1182/blood.2019000017
Abstract
Antigen-escape relapse has emerged as a major challenge for long-term disease control after CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. From March 2016 through January 2018, we conducted a pilot study in 89 patients who had refractory/relapsed B-cell malignancies, to evaluate the efficacy and safety of sequential infusion of anti-CD19 and anti-CD22, a cocktail of 2 single-specific, third-generation chimeric antigen receptor-engineered (CAR19/22) T cells. Among the 51 patients with acute lymphoblastic leukemia, the minimal residual disease-negative response rate was 96.0% (95% confidence interval [CI], 86.3-99.5). With a median follow-up of 16.7 months (range, 1.3-33.3), the median progression-free survival (PFS) was 13.6 months (95% CI, 6.5 to not reached [NR]), and the median overall survival (OS) was 31.0 months (95% CI, 10.6-NR). Among the 38 patients with non-Hodgkin lymphoma, the overall response rate was 72.2% (95% CI, 54.8-85.8), with a complete response rate of 50.0% (95% CI, 32.9-67.1). With a median follow-up of 14.4 months (range, 0.4-27.4), the median PFS was 9.9 months (95% CI, 3.3-NR), and the median OS was 18.0 months (95% CI, 6.1-NR). Antigen-loss relapse occurred in 1 patient during follow-up. High-grade cytokine release syndrome and neurotoxicity occurred in 22.4% and 1.12% patients, respectively. In all except 1, these effects were reversible. Our results indicated that sequential infusion of CAR19/22 T cell was safe and efficacious and may have reduced the rate of antigen-escape relapse in B-cell malignancies.This publication has 42 references indexed in Scilit:
- Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell LymphomaNew England Journal of Medicine, 2019
- Chimeric Antigen Receptor TherapyNew England Journal of Medicine, 2018
- CAR T cell immunotherapy for human cancerScience, 2018
- Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic LeukemiaNew England Journal of Medicine, 2018
- Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell LymphomaNew England Journal of Medicine, 2017
- Therapeutic T cell engineeringNature, 2017
- High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patientsLeukemia, 2017
- The Principles of Engineering Immune Cells to Treat CancerCell, 2017
- Immune targets and neoantigens for cancer immunotherapy and precision medicineCell Research, 2016
- T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trialThe Lancet, 2014