Manageable Safety Profile Observed in Phase 1 Studies Examining UCART19 for Pediatric and Adult Patients with B-Cell ALL

Data in The Lancet promoted a tolerable safety profile and future feasibility of UCART19 administration among patients with relapsed and refractory B cell ALL.

UCART19 produced a manageable safety profile in 2 separate phase 1 studies examining heavily pretreated pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), according to data published in The Lancet.

For the first time, these studies support the feasibility of UCART19 and other genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cells to treat this group of patients with aggressive forms of ALL.

“Phase 1 trials in paediatric and adult patients with late-stage relapsed or refractory B-cell acute lymphoblastic leukaemia have shown the feasibility, safety, and activity of UCART19, an off-the-shelf CAR T-cell product,” wrote the investigative team. “The results of these trials represent a substantial step forward in the development of CAR T cells and could herald a new, effective, and easily accessible cell therapy for patients with B-cell acute lymphoblastic leukaemia.”

The results determined that the most common adverse event between both phase 1 studies was cytokine release syndrome (CRS), observed in 19 patients (91%). Three patients (14%) experienced grade 3/4 CRS.

More, 8 patients (38%) experienced grades 1/2 neurotoxicity, 2 (10%) experienced grade 1 acute skin graft-versus-host disease, and 6 (32%) had grade 4 prolonged cytopenia.

The research team recorded 2 treatment-related deaths between the 2 studies. The first was caused by neutropenic sepsis in a patient with concurrent CRS and the other was from pulmonary hemorrhage in a patient with persistent cytopenia.

Overall, 14 of 21 patients (67%) experienced a complete response or complete response with incomplete hematological recovery at 28 days following infusion. Median duration of response was recorded at 4.1 months, with 10 of 14 adult patients (71%) progressing to subsequent allogeneic stem cell transplant. The progression-free survival rate at 6 months was 27%, with an overall survival rate of 55%.

“The adverse effects observed with UCART19 to date seem similar to those reported for autologous anti-CD19 CAR T cells,” wrote the investigators. “Cytokine release syndrome was encountered in the majority of patients in whom UCART19 expansion was detected and appeared no more severe than with approved autologous products.”

The 2 ongoing, multicenter, clinical trials (NCT02808442 and NCT02746952) enrolled 7 pediatric and 14 adult patients from June 3, 2016, through October 23, 2018, to examine the safety profile and antileukemic activity of UCART19.

The dose-escalation studies began with patients undergoing lymphodepletion with fludarabine and cyclophosphamide, with or without alemtuzumab (Lemtrada), followed by different doses of UCART19 for adults and children. The primary end point of the data was adverse events.

The small sample size for the investigation is the leading limitation for the research, but the research team also mentioned the differing trial designs, lymphodepletion regimens, and UCART19 cell doses to be among limitations of both trials.

“The results [of these studies] are an encouraging step forward for the field of allogeneic CAR T cells, and UCART19 offers the opportunity to treat patients with rapidly progressive disease and where autologous CAR T-cell therapy is unavailable,” wrote the investigators.


Benjamin R, Graham C, Yallop D, et al. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020;396(10266):1885-1894. doi: 10.1016/S0140-6736(20)32334-5