Parameters of long-term response with CD28-based CD19 chimaeric antigen receptor-modified T cells in children and...

CD28-based CD19 chimaeric antigen receptor-modified (CAR-)Tcells were recently FDA-approved for adult acute lymphoblastic leukaemia (ALL). We report long-term outcome of 37 children and young adults treated with autologous CD19 CAR-T cells. The complete remission rate was 86%, of which 71% were polymerase chain reaction (PCR) minimal residual disease (MRD)-negative, 14% were MRD-negative by flow cytometry, and 14% were PCR MRD-positive. 26 patients proceeded to subsequent haematopoietic stem cell transplant (HSCT). 11 patients had a CD19-postive relapse (eight post HSCT and three without) and one had a CD19-negative relapse. All relapse events occurred within two years from cell therapy. With a median follow-up of three years, the median event-free survival (EFS) is 17 months and the median overall survival (OS) is not reached. The three-year EFS is 41% and OS is 56%. Patients with >5% blasts in the bone marrow prior to lymphodepletion had an inferior EFS. All patients with a PCR MRD-positive result at day 28 had relapsed after CAR-T-cell therapy. A prior HSCT did not significantly affect outcome, but a consolidative transplant after achieving remission improved long-term results. Overall, prelymphodepletion disease burden and molecular MRD negativity following CAR-T cells are predictors of long-term outcome following CD19 CAR-T-cell therapy for ALL.