Intent to treat leukemia remission by CD19CAR T cells of defined formulation and dose in children and young adults.

Publication Type:

Journal Article


Blood (2017)


Transitioning CD19-directed CAR-T cells from early phase trials in relapsed patients to a viable therapeutic approach with predictable efficacy and low toxicity for broad application in patients with high unmet need is currently complicated by product heterogeneity resulting from transduction of undefined T cell mixtures, variability of transgene expression, and terminal differentiation of cells at the end of culture. A phase 1 trial of 45 children and young adults with relapsed or refractory B-lineage ALL was conducted using a CD19 CAR product of defined CD4/CD8 composition, uniform CAR expression, and limited effector differentiation. Products meeting all defined specifications occurred in 93% of enrolled subjects. The maximal tolerated dose (MTD) was 10(6) CAR-T cells/kg, and there were no deaths or instances of cerebral edema attributable to product toxicity. The overall intent-to-treat (ITT) minimal residual disease (MRD)-negative remission rate for this Phase I study was 89%. An MRD-negative remission rate measured among subjects who received a CAR T cell product was 93%, and 100% in the subset of patients that received flu/cy lymphodepletion. Twenty-three percent of patients developed reversible severe cytokine release syndrome (sCRS) and/or reversible severe neurotoxicity (sNT). These data demonstrate that manufacturing a defined composition CD19 CAR-T cell identifies an optimal cell dose with highly potent antitumor activity and a tolerable side effect profile in a cohort of patients with an otherwise dismal prognosis.