Sustained therapeutic efficacy of humanized anti-CD19 chimeric antigen receptor T cells in relapsed/refractory acute lymphoblastic leukemia

Purpose: Immunogenicity derived from the murine scFv, a major molecular compomemt of chimeric antigen receptors (CARs), may limit the persistence of CAR-T cells, resulting in tumor relapse of complete remission (CR) patients. In this study, we developed a humanized anti-CD19 scFv CAR-T (hCAR-T) to treat patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). Experimental Design: In this one-arm, open-labeled study, we infused the T cells modified with hCAR to patients with r/r ALL. Patients were evaluated with long term follow-up for response and safety of the treatment. The study was registered at Clinicaltrials.gov (NCT02349698). Results: Ten patients with r/r ALL were recruited for this study. All were response evaluable and all achieved CR; eight patients remained CR, and six were in CR for over 18 months without further treatment. A long-term persistence of hCAR-T cells was observed in most of the patients. Among these patients, four of them with high tumor burden and rapidly progressive disease (median 58%) experienced grade 3-4 CRS and neurotoxicity. These severe CRSs were successfully controlled by tocilizumab, glucocorticoid and plasma exchange (PE). Conclusions: T cells expressing the humanized anti-CD19 scFv CAR exhibited sustained therapeutic efficacy in the treatment of r/r ALL. Low replase rate was associated with the long-term persistence of CAR-T cells.