Safety and efficacy of a humanized CD19 chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic leukemia.
Ming ShiLi LiShiyuan WangHai ChengWei ChenWei SangKunming QiZhenyu LiGang WangHuizhong LiJianping LanJinqi HuangXiaoming FeiMin YuFei LiJianlin QiaoQingyun WuLingyu ZengGuangjun JingJunnian ZhengRobert Peter GaleKailin XuJiang CaoPublished in: American journal of hematology (2022)
CD19-targeted chimeric antigen receptor T (CAR-T) cells using murine single-chain variable fragment (scFv) has shown substantial clinical efficacy in treating relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, potential immunogenicity of the murine scFv domain may limit the persistence of CAR-T cells. In this study, we treated 52 consecutive subjects with R/R ALL with humanized CD19-specific CAR-T cells (hCART19s). Forty-six subjects achieved complete remission (CR) (N = 43) or CR with incomplete count recovery (CRi) (N = 3) within 1 month post infusion. During the follow-up with a median time of 20 months, the 1-year cumulative incidence of relapse was 25% (95% confidence interval [CI] 13-46), and 1-year event-free survival was 45% (95% CI 29-60). To the cutoff date, 20 patients presented CD19 + relapse and 2 had CD19 - relapse. Among the 22 relapsed patients, 14 had treatment-mediated and treatment-boosted antidrug antibodies (ADA) as detected in a sensitive and specific cell-based assay. ADA positivity was correlated with the disease relapse risk. ADA-positive patients had a significantly lower CAR copy number than ADA-negative patients at the time of recurrence (p < .001). In conclusion, hCART19s therapy is safe and highly active in R/R ALL patients, and the hCART19s treatment could induce the emergence of ADA, which is related to the recurrence of the primary disease.
Keyphrases
- acute lymphoblastic leukemia
- end stage renal disease
- free survival
- newly diagnosed
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- copy number
- prognostic factors
- cell death
- high throughput
- cell proliferation
- stem cells
- rheumatoid arthritis
- bone marrow
- mesenchymal stem cells
- multiple myeloma
- single cell
- risk factors
- signaling pathway
- drug delivery
- ulcerative colitis
- cancer therapy