Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials

Leuk Lymphoma. 2013 Feb;54(2):255-60. doi: 10.3109/10428194.2012.715350. Epub 2012 Sep 8.

Abstract

There remain some key questions regarding the adoptive infusion of chimeric antigen receptor (CAR) transduced T-cells in the clinical setting. This article systematically reviews the phase I clinical trials using CARs targeting CD19 in B-lineage malignancies. Twenty-nine patients were enrolled and the 6-month progression free survival for this cohort was 50.0 ± 9.9%. Univariate analysis showed that patients benefited from lymphodepletion before CAR+T-cell infusion and the administration of interleukin-2 (IL-2). Longer-term persistence (≥ 4 weeks) and stronger expansion of CAR+ T-cells in the blood and higher peak serum interferon-γ (IFN-γ) level (≥ 200 pg/mL) were also related to superior outcome. Regarding treatment-related adverse events, the most prominent toxicities were fever, rigors, chills, acute renal failure, hypotension and capillary leak syndrome. In conclusion, anti-CD19 CAR+ T-cells have shown some benefits in patients with B-lineage malignancies and are well tolerated in most patients. Preconditioning and cytokine supplement are required to improve the clinical outcome.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antigens, CD19 / immunology*
  • Clinical Trials, Phase I as Topic
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Leukemia, B-Cell / immunology
  • Leukemia, B-Cell / mortality
  • Leukemia, B-Cell / therapy*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / therapy*
  • Prognosis
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology*
  • Treatment Outcome

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell