HuCART19 Achieved Durable, Robust Responses in Adult and Pediatric R/R B-ALL

A new study has adapted CAR to look more human to the body, which will then in turn yield longer remission rates for pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.

Modified chimeric antigen receptor (CAR) product, human CAR T CD19 (huCART19), was found to yield long-term, efficacious remissions in adult and pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), according to the results of a phase 1 study (NCT02374333) published in the Journal of Clinical Oncology.1

Patients who had not previously received any CAR T-cell therapy experienced a complete response (CR)/ CR with incomplete count recovery (CRi) of 98% (n = 40/41) and 100% (n = 39/39) at day 28 following the infusion. All responders were minimal residual disease (MRD)–negative. In the retreatment cohort, the rate CR/CRi was 79% at day 28, with 86% of responders being MRD-negative. However, five patients did not have biologic response because B-cell aplasia was not established. One month following infusion, patients in the CAR T­–naïve arm had an overall response rate (ORR) of 98% vs 64% in the retreatment cohort. and after 1 and 2 years 74% and 58% remission rate respectively.

“These results show that [huCART19] is an encouraging option for retreatment in a difficult-to-treat population,” Shannon L. Maude, MD, PhD, an attending physician in the Cancer Center at CHOP and senior author of the study, said in a press release.2 “We are continuing to analyze the effectiveness of this approach in a phase 2 trial, which is ongoing.”

The open-label study enrolled 74 pediatric and young adults, from age 1 up to 29 years of age with either relapsed or refractory B-ALL (n = 72) or B-lymphoblastic lymphoma (BLL; n = 2). Investigators originally planned to administer a dose of 3 x 107 cells/kg with an acceptable range of 3 x 105 to 3 x 107 cells/kg with a maximum dose of 1.5 x 109 cells of huCART19 through an intravenous injection in patients who were 50 kg or more. Following an amendment to the base dose, the remaining 26 products were adjusted to 6 x 106huCART19 cells/kg with an acceptable range of 2 x 105 to 6 x 106 huCART19 cells/kg and a maximum dose of 5 x 108 huCART19 cells.

The study included 2 cohorts of patients who either had prior exposure or retreatment (B-ALL, n = 33) and patients who were CAR-naïve, without prior exposure 41 (B-ALL, n = 39; BLL, n = 2).

The primary end point of the study was safety and feasibility of huCART19 infusion, as well as duration of persistence. Key secondary end points included ORR at day 28, MRD-negative CR/CRi rate, event-free survival, OS, and an exploratory cytokine analysis.

The median follow-up was 21.2 months after infusion. Additional data from the study indicated patients in the CAR-naïve group experienced a 1-year relapse-free survival (RFS) rate of 84% (95% CI, 72-97) and a 2-year RFS rate of 74% (95% CI, 60-90), while the re-treatment arm had a 1- and 2-year RFS of 74% (95% CI, 56-97) and 58% (95% CI, 37-90), respectively. At 12 months, those who achieved CR/CRi with B-cell aplasia (n = 21) had a relapse-free survival rate of 74% (95% CI, 56%-97%). At 24 months, the RFS for this group was 58% (95% CI, 37%-90%). At 12 and 24 months, incidence of relapse was 24% (95% CI, 8%-44%) and 36% (95% CI, 15%-59%) respectively.

For patients who experienced a CR/CRi, 12 relapsed before undergoing additional therapy was received. Among this group, 6 were positive for CD19 cells, 4 were CD19-negative, and 2 had both positive and negative CD19 leukemic cells. At 6 months, patients who experienced B-cell aplasia had incidence of B-cell recovery 15% (95% CI, 6%-28%) in the CAR-naïve group and 58% (95% CI, 33%-77%) in retreatment group.

Some adverse effects (AEs) that patients experienced were cytokine release syndrome (CRS) occurring in 84% of patients, with 5 patients developing grade 4 effects. Neurologic toxicities occurred in 39% of patients that was of grade 3 (n=1) or grade 4 (n=1) and was fully resolved in all cases. Common serious AEs included CRS, febrile neutropenia, and encephalopathy. There were no treatment-related deaths noted by investigators during the study. All treatment-related AEs were reversible with the exception of persistent cytopenias past 8 weeks in 59% of the CAR-naïve cohort and 45% of the retreatment cohort.

“…The potential for improved persistence with huCART19, which may be associated with a decreased risk of relapse, warrants further study,” the authors of the study concluded.


1. Myers RM, Li Y, Barz Leahy A, et al. Humanized CD19-targeted chimeric antigen receptor (CAR) T Cells in CAR-naive and CAR-exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia. Published online ahead of print, June 22, 2021. J Clin Oncol. 2021. doi:10.1200/JCO.20.03458

2. CHOP researchers develop humanized CAR T-cell therapy that shows potential for patients with relapsed B-ALL. News Release. June 28, 2020. Accessed July 8, 2021.

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