Abstract
This study reports outcomes of Pediatric Leukemia Adoptive Therapy 02 (PLAT-02), a phase 2 trial of SCRI-CAR19, a second-generation chimeric antigen receptor (CAR) T-cell product with FMC63 single-chain variable fragment and 4-1BB costimulation, in pediatric and young adult patients with B-cell acute lymphoblastic leukemia; and PLAT-03, a companion study evaluating exogenous CD19 antigen stimulation with serial infusions of T cells expressing truncated CD19, T-cell antigen-presenting cells (T-APCs). The efficacy cohort of PLAT-02 (n = 72 patients; median age 12.5 years) received fludarabine/cyclophosphamide lymphodepletion followed by a dose of 1 × 106 CAR+ T cells per kg. The minimal residual disease-negative complete remission rate was 89%. Leukemia-free survival (LFS) at 1 and 2 years was 0.71 (95% confidence interval [CI], 0.58-0.81) and 0.64 (95% CI, 0.51-0.75), respectively. Patients with low disease burden had significantly higher 1-year LFS (0.91 vs 0.42). Rapid in vivo contraction of CAR T cells after infusion was associated with CAR loss within 6 months compared to those without rapid contraction (57% vs 19%). Most common grade 3/4 adverse events included cytokine release syndrome in 13% and neurotoxicity in 16%. The companion pilot, PLAT-03, enrolled 26 patients, and 19 received T-APCs. Neither cytokine-release syndrome nor neurotoxicity was observed after T-APC infusion. T-APC infusions in patients improved persistence (P = .03), with rapid CAR T-cell contraction being associated with decreased early CAR loss (20% with T-APC vs 57% without). Further exploration of serial artificial CD19 antigen exposure is warranted based on these pilot results. PLAT-02 and PLAT-03 trials were registered at www.clinicaltrials.gov as #NCT02028455 and #NCT03186118, respectively.