Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials.
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.
Division of Hematology-Oncology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou, PR China.
Xiao-Jun
XJ
Xu
Hai-Zhao
HZ
Zhao
Yong-Min
YM
Tang
D018941:Antigens, CD19 / Q000276:immunology*; D017321:Clinical Trials, Phase I as Topic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D015448:Leukemia, B-Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D018941:Antigens, CD19; D011948:Receptors, Antigen, T-Cell